{"id":"breast-her2-positive","kind":"indication","name":"HER2-positive breast cancer","aka":[],"tldr":"HER2-positive breast cancer was once the most aggressive subtype and is now one of the most treatable, thanks to trastuzumab and, more recently, Enhertu.","summary":"HER2-positive breast cancer (15-20% of cases; HER2 IHC 3+ or ISH-amplified) was the most aggressive subtype until trastuzumab (1998) made it one of the most treatable. The modern curative pathway is response-adapted: neoadjuvant chemotherapy with dual HER2 blockade (or, since 2026, T-DXd followed by THP), surgery, then either antibody completion for patients with a pathologic complete response or an ADC for residual disease (T-DM1 from KATHERINE, now T-DXd from DESTINY-Breast05). Small node-negative tumours are cured with paclitaxel-trastuzumab alone; PHERGain showed that an early PET response can spare a third of patients chemotherapy altogether. Extended adjuvant neratinib and adjuvant pertuzumab add small gains in higher-risk, node-positive disease.\n\nMetastatic disease has been transformed twice: by CLEOPATRA's pertuzumab (OS 57 months) and then by trastuzumab deruxtecan, which beat T-DM1 by a wide margin in second line (DESTINY-Breast03) and beat THP in first line (DESTINY-Breast09, PFS 40.7 months; approved 2025). Brain metastases, which develop in up to half of patients, are now treatable systemically with tucatinib (HER2CLIMB) and T-DXd (DESTINY-Breast12). HER2CLIMB-05 (tucatinib maintenance) and PATINA (palbociclib maintenance in HR+/HER2+, approved 2026) intensify chemotherapy-free maintenance, and a wave of Chinese HER2 ADCs (trastuzumab rezetecan, BL-M07D1, ARX788, disitamab vedotin) is producing Enhertu-scale results.\n\nOpen problems are the sequencing of HER2 ADCs after T-DXd (payload cross-resistance), interstitial lung disease, cardiotoxicity across years of therapy, the cost and duration of antibody therapy, brain metastases prevention, and de-escalation: identifying the substantial fraction of patients who are over-treated. The pipeline is defined by T-DXd's move into every curative setting, tucatinib-based maintenance, next-generation and biparatopic HER2 ADCs (zanidatamab zovodotin), HER2 CAR-T and vaccines, and imaging- and ctDNA-adapted de-escalation trials.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/HER2-positive_breast_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HER2-positive_breast_cancer"}],"tags":["breast","spike"],"related":[],"indications":[],"sections":[],"technologies":["her2-pet","fdg-pet","site-specific-conjugation"],"targets":["her2"],"drugs":[],"companies":["astrazeneca","pfizer","johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":["phergain"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"breast","burden":"15-20% of breast cancers (roughly 400,000 cases per year worldwide). Ten-year survival for early-stage disease treated with trastuzumab-based therapy exceeds 80%.","subtypes":["HER2-enriched (PAM50; highest pCR rates to HER2 blockade)","HR+/HER2+ ('triple-positive', ~50% of HER2+; lower pCR, endocrine therapy and CDK4/6 maintenance relevant)","HR-/HER2+ (higher pCR, more relapse in first 3 years)","HER2-mutant (activating mutations without amplification; T-DXd tumour-agnostic, HER2 TKIs; more common in lobular and HER2-low)","HER2 heterogeneous tumours (mixed amplified and non-amplified clones; lower pCR)","Small node-negative (stage I) disease cured by de-escalated therapy"],"biomarkers":["HER2 IHC 3+ or ISH-amplified","HR status","pCR after neoadjuvant therapy","HER2 IHC 3+ or IHC 2+ with ISH amplification (ASCO/CAP 2018 criteria); HER2 heterogeneity","HR status (drives triple-positive management, PATINA eligibility)","Pathologic complete response after neoadjuvant therapy (selects T-DM1/T-DXd post-neoadjuvant)","Early FDG-PET response (PHERGain de-escalation)","LVEF by echocardiography or MUGA every 3 months on anti-HER2 therapy","Brain MRI when symptomatic; surveillance MRI debated","HER2 status on re-biopsy at progression (conversion in 10-15%)","PIK3CA mutation (lower pCR; INAVO122 tests inavolisib in HER2+)","ctDNA MRD (investigational for post-neoadjuvant escalation)"],"standardOfCare":[{"setting":"Early stage","approach":"Neoadjuvant THP or T-DXd → surgery → trastuzumab/pertuzumab (pCR) or T-DXd/T-DM1 (residual).","refs":[],"guideline":{"nccn":"Category 1, preferred: neoadjuvant pertuzumab + trastuzumab + chemotherapy; adjuvant trastuzumab; T-DM1 for residual disease Category 1","esmoMcbs":"A (KATHERINE); A (HERA); C (NeoSphere, APHINITY)","version":"NCCN Guidelines: Breast Cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13114725/"}},{"setting":"Metastatic","approach":"T-DXd + pertuzumab first line (DESTINY-Breast09); tucatinib + trastuzumab + capecitabine for brain metastases; palbociclib maintenance if HR+.","refs":[],"guideline":{"esmoMcbs":"4 (DESTINY-Breast03); 4 (CLEOPATRA); 4 (HER2CLIMB)","version":"NCCN Guidelines: Breast Cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13114725/"}},{"setting":"Stage I (≤2-3 cm, node-negative)","approach":"Surgery then weekly paclitaxel × 12 + trastuzumab × 1 year (APT); T-DM1 × 17 cycles is an alternative (ATEMPT). Endocrine therapy if HR+.","refs":[],"guideline":{"nccn":"2A","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Stage II-III, neoadjuvant","approach":"TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) or anthracycline-taxane + HP; from 2026, T-DXd × 4 → THP (DESTINY-Breast11, pCR 67%). PET-adapted chemotherapy omission (PHERGain) in trials.","refs":["phergain"],"guideline":{"nccn":"1","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Post-neoadjuvant, pathologic complete response","approach":"Complete 1 year of trastuzumab (± pertuzumab if node-positive at diagnosis); endocrine therapy if HR+; radiation per stage.","refs":[],"guideline":{"nccn":"1","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Post-neoadjuvant, residual invasive disease","approach":"T-DXd (DESTINY-Breast05, iDFS HR 0.47 vs T-DM1; approved 2026) replacing T-DM1 (KATHERINE); consider extended adjuvant neratinib for HR+ high-risk.","refs":[],"guideline":{"nccn":"1 (T-DM1); T-DXd pending update","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Adjuvant (upfront surgery), node-positive","approach":"Chemotherapy + trastuzumab + pertuzumab for 1 year (APHINITY); trastuzumab alone for lower risk; 6 months acceptable where resources are limited (PERSEPHONE).","refs":[],"guideline":{"nccn":"1","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Metastatic, first line","approach":"T-DXd + pertuzumab (DESTINY-Breast09, PFS 40.7 months; approved 2025) or taxane + trastuzumab + pertuzumab (CLEOPATRA) followed by maintenance: HP ± tucatinib (HER2CLIMB-05) and, if HR+, endocrine therapy + palbociclib (PATINA, approved 2026).","refs":[],"guideline":{"nccn":"1, preferred (T-DXd + pertuzumab)","esmoMcbs":"4 (CLEOPATRA)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Metastatic, second line","approach":"T-DXd if not used first line (DESTINY-Breast03, PFS HR 0.33 vs T-DM1); tucatinib + trastuzumab + capecitabine, especially with brain metastases (HER2CLIMB).","refs":[],"guideline":{"nccn":"1","esmoMcbs":"4 (DESTINY-Breast03)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Metastatic, later lines","approach":"T-DM1; neratinib or lapatinib + capecitabine; margetuximab + chemotherapy; trastuzumab + chemotherapy (continued HER2 blockade); zanidatamab and Chinese ADCs (trastuzumab rezetecan, disitamab vedotin) where available; trials.","refs":[],"guideline":{"nccn":"2A","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Brain metastases","approach":"Systemic: tucatinib triplet or T-DXd (DESTINY-Breast12, intracranial ORR 72%); local: stereotactic radiosurgery or surgery for symptomatic or large lesions; whole-brain RT reserved.","refs":[],"guideline":{"nccn":"1 (tucatinib triplet)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}},{"setting":"Cardiac monitoring and survivorship","approach":"LVEF every 3 months during anti-HER2 therapy; hold and cardioprotect for declines; anthracycline-free regimens preferred; long-term surveillance for late recurrence in HR+/HER2+.","refs":[]}],"stateOfArt":["T-DXd across the disease continuum.","Chemotherapy de-escalation guided by early response.","Ten-year survival above 80% for early disease: the subtype with the poorest outlook in the 1990s is now one of the most treatable.","Response-adapted curative therapy: pCR patients de-escalate, residual disease escalates to an ADC (now T-DXd, iDFS HR 0.47 vs T-DM1).","T-DXd across the continuum: neoadjuvant (2026), post-neoadjuvant (2026), first-line metastatic with pertuzumab (2025, PFS 40.7 months), second line, and brain metastases.","Systemic control of brain metastases (tucatinib, T-DXd) allowing deferral of radiation.","Chemotherapy-free maintenance intensification: tucatinib (HER2CLIMB-05) and palbociclib for HR+/HER2+ (PATINA).","Chemotherapy omission for a third of patients using early PET response (PHERGain)."],"history":[{"year":1987,"title":"Slamon shows HER2 amplification marks aggressive disease, and a drug target","refs":[]},{"year":1987,"title":"Slamon shows HER2 amplification marks aggressive disease, and a drug target","note":"Science paper identifying HER2/neu amplification in 25-30% of breast cancers.","refs":["her2"]},{"year":1998,"title":"Trastuzumab approved","refs":[]},{"year":1998,"title":"Trastuzumab approved for metastatic disease","note":"First antibody for a solid tumour; OS benefit with chemotherapy.","refs":[]},{"year":2005,"title":"Adjuvant trastuzumab halves recurrence (HERA, B-31/N9831)","refs":[]},{"year":2007,"title":"Lapatinib: first HER2 pill","refs":[]},{"year":2012,"title":"Pertuzumab and dual blockade (CLEOPATRA)","refs":[]},{"year":2013,"title":"First solid-tumour ADC: T-DM1","refs":[]},{"year":2013,"title":"T-DM1: first solid-tumour ADC; pertuzumab first pCR-based approval","refs":[]},{"year":2015,"title":"APT: de-escalation for small tumours","refs":[]},{"year":2017,"title":"First trastuzumab biosimilar; neratinib; APHINITY","refs":[]},{"year":2018,"title":"KATHERINE: T-DM1 for residual disease","refs":[]},{"year":2019,"title":"T-DXd approved; HER2CLIMB proves CNS benefit","refs":[]},{"year":2020,"title":"Tucatinib, margetuximab, Phesgo approved","refs":[]},{"year":2021,"title":"T-DXd beats T-DM1 (DESTINY-Breast03)","refs":[]},{"year":2021,"title":"DESTINY-Breast03: T-DXd beats T-DM1","refs":[]},{"year":2024,"title":"PHERGain chemotherapy omission; DESTINY-Breast12 brain metastases; zanidatamab approved (BTC)","refs":["phergain"]},{"year":2025,"title":"DESTINY-Breast09 first-line approval; DESTINY-Breast05 and HER2CLIMB-05 positive; trastuzumab rezetecan approved (China, NSCLC)","refs":[]},{"year":2026,"title":"T-DXd approved in early-stage disease","refs":[]},{"year":2026,"title":"T-DXd approved neoadjuvant and post-neoadjuvant; palbociclib maintenance for HR+/HER2+ (PATINA)","refs":[]}],"pipeline":["her2-pet","phergain"],"openProblems":["Brain metastases in ~50% of metastatic patients.","Which patients can skip chemotherapy entirely.","Sequencing after T-DXd: no randomised data on which HER2 ADC or TKI works after TOP1-payload failure.","Interstitial lung disease with T-DXd in curative settings, where patients would otherwise be cured.","Over-treatment: which patients need pertuzumab, a full year of antibodies, or any chemotherapy at all (PHERGain-2, response-adapted trials).","Brain metastasis prevention and whether systemic-first strategies preserve cognition.","HR+/HER2+ ('triple-positive') disease: optimal integration of endocrine therapy, CDK4/6 inhibitors, and HER2 blockade.","Cardiotoxicity surveillance burden versus event rates in low-risk patients.","Global access: biosimilars have widened trastuzumab access but pertuzumab, T-DM1, and T-DXd remain unavailable in much of the world.","HER2 heterogeneity and HER2 conversion at relapse require re-biopsy strategies or HER2 PET."],"route":"/indications/breast-her2-positive/"}
{"id":"dlbcl","kind":"indication","name":"Diffuse large B-cell lymphoma","aka":[],"tldr":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive but curable lymphoma. CAR-T cures about 40% of relapsed patients, and off-the-shelf bispecifics are now approved.","summary":"Diffuse large B-cell lymphoma is the most common aggressive lymphoma, about 30% of all non-Hodgkin lymphoma, with a median age around 65. It is curable: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) cures roughly 60% of patients, more with low IPI and fewer with high-risk features (IPI 3-5, double-hit MYC/BCL2 rearrangement, activated B-cell origin, TP53 loss). Staging uses PET-CT and the Lugano classification; biology is read from cell of origin and FISH for MYC, BCL2 and BCL6, with genetic classifiers (LymphGen) and ctDNA emerging.\n\nFrontline therapy stood still for twenty years until POLARIX (2022) showed that replacing vincristine with the CD79b ADC polatuzumab vedotin improves progression-free survival (5-year 64.9% vs 59.1%), and frontMIND (Lancet 2026) showed tafasitamab plus lenalidomide added to R-CHOP improves PFS in IPI 3-5 disease (HR 0.75); epcoritamab plus R-CHOP (EPCORE DLBCL-2) and golcadomide plus R-CHOP (GOLSEEK-1) follow. For the 30-40% who relapse, the sequence has been rebuilt around T-cell redirection: CD19 CAR-T (axi-cel, liso-cel) beats salvage chemotherapy and transplant for relapse within a year (ZUMA-7 with an overall survival benefit; TRANSFORM), while transplant remains for later chemosensitive relapse. Off-the-shelf CD20×CD3 bispecifics (glofitamab, epcoritamab, mosunetuzumab, odronextamab) give complete remissions in about 40% of heavily pretreated patients, and chemotherapy-free doublets such as mosunetuzumab-polatuzumab (SUNMO) beat salvage chemotherapy. CD19 ADC (loncastuximab), tafasitamab-lenalidomide, and the ROR1 ADC zilovertamab vedotin fill later lines.\n\nThe open questions are regulatory as much as scientific. EPCORE DLBCL-1 (2026) improved PFS but not overall survival against chemotherapy; STARGLO's survival benefit was rejected by the FDA because the trial was mostly enrolled in Asia. Nobody has compared bispecifics with CAR-T head to head. ctDNA (PhasED-seq) predicts cure better than PET and is the obvious tool for response-adapted frontline therapy. Primary refractory disease, CNS relapse, older and frail patients, and access to CAR-T outside major centres remain the hard problems.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma"}],"tags":["heme","spike"],"related":["follicular-lymphoma"],"indications":[],"sections":[],"technologies":["fdg-pet"],"targets":["cd20"],"drugs":[],"companies":["bms","merck","novartis"],"institutions":["mskcc","md-anderson","dana-farber","mayo-clinic"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"~150,000 new cases a year worldwide; ~25,000 in the US; median age 65; about 60% cured with first-line therapy.","subtypes":["Germinal-centre B-cell-like (GCB) vs activated B-cell-like (ABC / non-GCB)","High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double hit)","LymphGen genetic subtypes: MCD, BN2, N1, EZB, ST2, A53","Primary mediastinal B-cell lymphoma (distinct; PD-1 responsive)","Primary CNS lymphoma (distinct; methotrexate-based)","Transformed indolent lymphoma (Richter, transformed follicular)","EBV-positive DLBCL of the elderly","Primary refractory vs early relapse (<12 months) vs late relapse"],"biomarkers":["Cell of origin (GCB/ABC)","Double-hit (MYC/BCL2)","CD19/CD20","ctDNA MRD","IPI / NCCN-IPI","Cell of origin (Hans IHC, Lymph2Cx)","MYC, BCL2, BCL6 FISH","TP53 mutation","CD19 and CD20 expression (loss after CAR-T or bispecific)","Interim and end-of-treatment PET (Deauville)","ctDNA (PhasED-seq, clonoSEQ)","LDH","CNS-IPI for CNS prophylaxis decisions"],"standardOfCare":[{"setting":"Frontline","approach":"R-CHOP or Pola-R-CHP.","refs":[],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Early relapse","approach":"CD19 CAR-T.","refs":[],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Later","approach":"CD20×CD3 bispecifics, loncastuximab, tafasitamab.","refs":[],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Limited stage (I-II, non-bulky)","approach":"R-CHOP × 4 with PET-guided omission of radiation (FLYER, S1001): 4 cycles if interim PET negative; involved-site radiotherapy if PET positive.","refs":["fdg-pet"],"guideline":{"nccn":"Category 1 (R-CHOP × 4 PET-adapted for stage I-II)","version":"NCCN B-Cell Lymphomas 2026","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Advanced stage, IPI 0-1","approach":"R-CHOP × 6 (or Pola-R-CHP); consider 4 cycles plus 2 rituximab in young low-risk patients (FLYER).","refs":[],"guideline":{"nccn":"Category 1","version":"NCCN 2026"}},{"setting":"Advanced stage, IPI 2-5","approach":"Pola-R-CHP × 6 (POLARIX) or R-CHOP × 6; tafasitamab + lenalidomide + R-CHOP (frontMIND) pending approval for IPI 3-5; DA-EPOCH-R for double-hit lymphoma; CNS prophylaxis for high CNS-IPI (contested).","refs":[],"guideline":{"nccn":"Pola-R-CHP category 1 for IPI 2-5","version":"NCCN 2026"}},{"setting":"Frail or elderly","approach":"R-mini-CHOP; epcoritamab-based regimens in trials for the elderly (EPCORE NHL-2 cohorts); tafasitamab-lenalidomide where transplant is never an option.","refs":[]},{"setting":"Primary refractory or relapse within 12 months","approach":"CD19 CAR-T (axi-cel or liso-cel) preferred over salvage chemotherapy and transplant (ZUMA-7, TRANSFORM); bridging therapy while manufacturing; bispecific ± chemotherapy if CAR-T unavailable.","refs":[],"guideline":{"nccn":"Category 1 (axi-cel, liso-cel)","version":"NCCN 2026"}},{"setting":"Late relapse (>12 months), transplant-eligible","approach":"Salvage chemotherapy (R-ICE, R-DHAP, R-GemOx) → high-dose therapy and autologous transplant if chemosensitive; CAR-T if not.","refs":[]},{"setting":"Relapse, transplant-ineligible","approach":"CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine.","refs":[]},{"setting":"Third line and beyond","approach":"CAR-T if not yet given; bispecific after CAR-T (active in CD19-negative relapse if CD20 retained); loncastuximab; zilovertamab vedotin (trial); allogeneic transplant in selected fit patients; clinical trials.","refs":[]}],"stateOfArt":["CAR-T second line.","Bispecifics as off-the-shelf T-cell therapy.","Frontline has moved: Pola-R-CHP (POLARIX) is standard for IPI 2-5, and frontMIND (tafasitamab-lenalidomide-R-CHOP) is the first phase 3 to beat R-CHOP in IPI 3-5 disease since rituximab.","CD19 CAR-T is second-line standard for early relapse, with an overall survival benefit in ZUMA-7 (4-year OS 54.6% vs 46.0%).","Four CD20×CD3 bispecifics approved or conditionally approved worldwide give ~40% complete remissions off the shelf; chemotherapy-free doublets (mosun-pola) beat salvage chemotherapy.","ctDNA by phased-variant sequencing detects residual lymphoma below PET sensitivity and is entering response-adapted trials.","Regulators now scrutinise generalisability (STARGLO CRL) and demand overall survival for confirmatory bispecific trials (EPCORE DLBCL-1 missed OS)."],"history":[{"year":1976,"title":"CHOP regimen introduced","note":"Cyclophosphamide, doxorubicin, vincristine, prednisone becomes the backbone for aggressive lymphoma.","refs":[]},{"year":1993,"title":"CHOP proves equal to more intensive regimens; IPI published","refs":[]},{"year":1997,"title":"Rituximab: first antibody for cancer","refs":[]},{"year":1997,"title":"Rituximab: first monoclonal antibody approved for cancer","refs":["cd20"]},{"year":2000,"title":"Gene-expression profiling defines GCB and ABC subtypes","refs":[]},{"year":2002,"title":"GELA LNH-98.5: R-CHOP improves survival over CHOP","note":"Rituximab added to CHOP raises cure rates by ~15 points; the standard for the next twenty years.","refs":[]},{"year":2014,"title":"Lugano classification unifies PET-based staging and response","refs":["fdg-pet"]},{"year":2017,"title":"Axi-cel CAR-T approved","refs":[]},{"year":2017,"title":"Axi-cel: first CAR-T approved for large B-cell lymphoma (ZUMA-1)","refs":[]},{"year":2019,"title":"Polatuzumab vedotin approved with BR for relapsed disease","refs":[]},{"year":2020,"title":"Tafasitamab-lenalidomide (L-MIND) approved for transplant-ineligible relapse","refs":[]},{"year":2021,"title":"Loncastuximab tesirine approved; BELINDA fails while ZUMA-7 and TRANSFORM succeed","refs":[]},{"year":2022,"title":"ZUMA-7: CAR-T beats transplant","refs":[]},{"year":2022,"title":"POLARIX: first frontline improvement on R-CHOP in twenty years; CAR-T approved second line","refs":[]},{"year":2023,"title":"Glofitamab, epcoritamab approved","refs":[]},{"year":2023,"title":"Glofitamab and epcoritamab approved: off-the-shelf T-cell redirection","refs":[]},{"year":2024,"title":"STARGLO shows OS benefit for glofitamab-GemOx; odronextamab approved in EU","refs":[]},{"year":2025,"title":"SUNMO positive (mosun-pola); FDA rejects STARGLO indication over applicability; POLARIX 5-year data","refs":[]},{"year":2026,"title":"frontMIND published in Lancet; EPCORE DLBCL-1 misses OS; frontline bispecific data (EPCORE DLBCL-2) at EHA","refs":[]}],"pipeline":[],"openProblems":["Primary refractory disease.","CAR-T access and cost.","Primary refractory disease (~10-15%) still has poor outcomes even with CAR-T; CD19-negative and CD20-negative escape after targeted therapy.","No head-to-head comparison of bispecifics and CAR-T; sequencing is by access rather than evidence.","Overall survival is hard to demonstrate for bispecifics against chemotherapy with crossover and effective later lines (EPCORE DLBCL-1).","Trial generalisability: STARGLO's rejection shows regional enrolment can decide approvals.","CNS relapse: prophylaxis with high-dose methotrexate is of uncertain benefit and CNS-penetrant options are few.","Older and frail patients are underrepresented; R-mini-CHOP cure rates lag and cellular therapies carry toxicity.","Cost and access: CAR-T requires certified centres; bispecific CRS management needs infrastructure; lenalidomide-based triplets add expense.","Response-adapted therapy: interim PET is unreliable and ctDNA is not yet a regulatory endpoint."],"route":"/indications/dlbcl/"}
{"id":"follicular-lymphoma","kind":"indication","name":"Follicular lymphoma","aka":[],"tldr":"Follicular lymphoma is the most common slow-growing lymphoma, defined in about 85% of cases by a BCL2 translocation. Most people live with it for decades, treated only when it causes problems; it can be controlled repeatedly with anti-CD20 antibodies, chemotherapy, bispecifics or CAR-T but rarely cured, and a small share transform into an aggressive lymphoma each year.","summary":"Follicular lymphoma (FL) is an indolent germinal-centre B-cell lymphoma defined by t(14;18) BCL2 overexpression in ~85% and frequent CREBBP, KMT2D and EZH2 mutations. Median survival now exceeds 15-20 years, so the questions are when to treat, how to avoid over-treatment, and how to manage the ~20% who progress within 24 months (POD24) and the 2-3% per year who transform to DLBCL.\n\nAsymptomatic low-burden disease is watched or given rituximab monotherapy; symptomatic or high-burden disease receives anti-CD20 (rituximab or obinutuzumab) with bendamustine, CHOP or CVP, or with lenalidomide (R², RELEVANCE), usually followed by anti-CD20 maintenance (PRIMA). Relapsed disease has the richest menu in lymphoma: lenalidomide-rituximab (AUGMENT), CD20×CD3 bispecifics (mosunetuzumab 2022, epcoritamab 2024, odronextamab EU), CD19 CAR-T (axicabtagene 2021, tisagenlecleucel 2022, lisocabtagene 2024), zanubrutinib-obinutuzumab (ROSEWOOD, 2024) and radioimmunotherapy historically. Tazemetostat (EZH2) was withdrawn worldwide in March 2026.\n\nOpen questions: whether bispecifics or CAR-T should move to second line or even first line (EPCORE FL-1, MorningSun), PET/ctDNA-guided de-escalation, and biology-based prediction of POD24 and transformation.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Follicular_lymphoma","links":[{"label":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"},{"label":"NCI PDQ: adult NHL","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq"},{"label":"Lymphoma Research Foundation: FL","url":"https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/fl/"}],"tags":["gap-fill","haematologic"],"related":["dlbcl"],"indications":[],"sections":[],"technologies":["pet-ct","radioimmunotherapy"],"targets":["cd20"],"drugs":["rituximab","ibritumomab-tiuxetan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Follicular lymphoma is the second most common non-Hodgkin lymphoma in the West (~20% of NHL; about 3-4 per 100,000 per year), median age ~65.","subtypes":["Classic FL (grades 1-3A)","Follicular large B-cell lymphoma (formerly 3B)","FL with unusual cytological features","Duodenal-type FL","Paediatric-type FL","Transformed FL"],"biomarkers":["t(14;18)/BCL2","FLIPI / FLIPI2 / m7-FLIPI","PET-CT (Lugano) staging and end-of-induction response","POD24 (progression within 24 months)","EZH2 mutation","ctDNA (investigational MRD)"],"standardOfCare":[{"setting":"Limited stage (I-II)","approach":"Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.","refs":["rituximab"],"guideline":{"nccn":"Category 1 (ISRT)","version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Advanced, low burden, asymptomatic","approach":"Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy.","refs":["rituximab"]},{"setting":"Advanced, high burden (GELF criteria)","approach":"Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA).","refs":["rituximab"],"guideline":{"nccn":"Category 1","esmoMcbs":"3 (GALLIUM)","version":"NCCN Guidelines: B-Cell Lymphomas"}},{"setting":"Relapsed (≥2 lines)","approach":"Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials.","refs":[],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: B-Cell Lymphomas"}}],"stateOfArt":["Chemotherapy-free options now exist at every line: R² first line, bispecifics and BTK-anti-CD20 combinations at relapse.","CAR-T gives durable remissions in heavily pretreated FL (ZUMA-5 ~50% progression-free at 4 years) and is being tested against bispecifics.","POD24 identifies the high-risk fifth; how to treat them differently up front is still unknown.","Trials of bispecific plus lenalidomide first line (EPCORE FL-2, CELESTIMO) will decide whether chemotherapy leaves front-line FL."],"history":[{"year":1984,"title":"t(14;18) links BCL2 to follicular lymphoma","note":"Tsujimoto and Croce clone the breakpoint; BCL2 becomes the first anti-apoptotic oncogene.","refs":[]},{"year":1997,"title":"Rituximab approved","note":"First monoclonal antibody for cancer, in relapsed indolent lymphoma.","refs":["rituximab"]},{"year":2004,"title":"FLIPI prognostic index","refs":[]},{"year":2011,"title":"PRIMA: rituximab maintenance","note":"Two years of maintenance doubles PFS after chemo-immunotherapy.","refs":["rituximab"]},{"year":2017,"title":"Obinutuzumab first line (GALLIUM)","refs":[]},{"year":2018,"title":"RELEVANCE: chemo-free R²","note":"Lenalidomide-rituximab matches chemo-immunotherapy first line.","refs":[]},{"year":2021,"title":"CAR-T enters FL","note":"Axicabtagene (ZUMA-5) approved; tisagenlecleucel (ELARA) 2022; lisocabtagene 2024.","refs":[]},{"year":2022,"title":"First bispecific: mosunetuzumab","note":"Off-the-shelf CD20×CD3 with ~60% CR in third line.","refs":[]},{"year":2024,"title":"Epcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL","refs":[]},{"year":2026,"title":"Tazemetostat withdrawn worldwide","note":"Secondary haematologic malignancies; EZH2 leaves the FL armamentarium.","refs":[]}],"pipeline":[],"openProblems":["Transformation to DLBCL cannot be predicted or prevented.","Sequencing bispecifics vs CAR-T.","Whether earlier intensive therapy for POD24 patients improves survival.","Late toxicities of decades of therapy (secondary cancers, infections, immunoglobulin loss)."],"route":"/indications/follicular-lymphoma/"}
{"id":"glioblastoma","kind":"indication","name":"Glioma & glioblastoma","aka":[],"tldr":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions.","summary":"Gliomas are classified by the WHO 2021 system on molecular grounds: IDH-wild-type glioblastoma (grade 4, ~50% of gliomas, median age 65, median survival ~15 months with maximal therapy), IDH-mutant astrocytoma (grades 2-4) and 1p/19q-codeleted oligodendroglioma (better prognosis, decades of survival possible), and paediatric-type tumours including H3 K27M-mutant diffuse midline glioma (median survival ~11 months) and BRAF-altered low-grade glioma (the commonest childhood brain tumour, rarely life-threatening but chronically disabling). The two shared barriers are the blood-brain barrier, which excludes most drugs, and diffuse infiltration, which makes complete resection impossible.\n\nGlioblastoma treatment has been static since 2005: maximal safe resection (improved by 5-ALA fluorescence, intraoperative MRI, and awake mapping; the extent of resection is itself prognostic and is now graded by the RANO resect classes), radiotherapy with concurrent and adjuvant temozolomide (Stupp), and tumour treating fields (EF-14). MGMT promoter methylation predicts temozolomide benefit; unmethylated tumours gain less, though not nothing, and how much remains debated (in the elderly trials NOA-08 and Nordic, unmethylated tumours did better with radiotherapy than with temozolomide alone). Every major systemic trial since has failed: bevacizumab (PFS only), rindopepimut (ACT IV), nivolumab (CheckMate 143, 498, 548), depatuxizumab mafodotin (INTELLANCE-1), and many more. At recurrence, lomustine, re-resection, re-irradiation, LITT, and bevacizumab for oedema are the options, with median survival under a year. DCVax-L's externally controlled phase 3 remains contested.\n\nProgress has come at the edges. Vorasidenib (INDIGO, approved 2024) is the first targeted therapy for grade 2 IDH-mutant glioma, delaying radiation and chemotherapy by years. Dabrafenib with trametinib (2023) was the first targeted therapy approved for BRAF V600E paediatric low-grade glioma; tovorafenib (2024) followed for relapsed or refractory BRAF-altered tumours, including BRAF fusions. Dordaviprone (August 2025) is the first drug approved for H3 K27M diffuse midline glioma. Methylation-based classification and intraoperative nanopore sequencing have transformed diagnosis. For glioblastoma itself the most promising directions are locoregional CAR-T (IL13Rα2, GD2, multi-target), focused-ultrasound and LITT-based barrier opening to deliver ADCs, radioconjugates, and chemotherapy, neoadjuvant immunotherapy with window designs, personalised neoantigen vaccines (NeoVax), and combinations built on the unmethylated-MGMT population where temozolomide adds nothing.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Glioblastoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glioblastoma"}],"tags":["cns","spike"],"related":["meningioma"],"indications":[],"sections":[],"technologies":[],"targets":["b7h3"],"drugs":[],"companies":["bms"],"institutions":["penn-abramson","heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"central nervous system","burden":"About 300,000 CNS tumours occur per year, most of them not glioblastoma; IDH-mutant and paediatric low-grade gliomas can be lived with for decades and now have targeted drugs. Median survival for glioblastoma with maximal therapy is about 15 months.","subtypes":["Glioblastoma, IDH-wild-type (WHO grade 4; TERT promoter, EGFR amplification, +7/−10)","Astrocytoma, IDH-mutant (grades 2-4; CDKN2A/B deletion defines grade 4)","Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (grades 2-3)","Diffuse midline glioma, H3 K27M-altered (including DIPG)","Paediatric low-grade glioma (BRAF fusion or V600E, NF1)","Diffuse hemispheric glioma H3 G34-mutant; infant-type hemispheric glioma (NTRK/ALK/ROS1 fusions)"],"biomarkers":["IDH1/2","1p/19q codeletion","MGMT methylation","H3K27M","EGFR amplification","Methylation class","IDH1/2 mutation (vorasidenib eligibility)","MGMT promoter methylation (temozolomide benefit)","H3 K27M (dordaviprone eligibility)","BRAF fusion / V600E (tovorafenib, dabrafenib-trametinib)","TERT promoter, EGFR amplification, +7/−10 (molecular glioblastoma)","CDKN2A/B homozygous deletion (grade 4 astrocytoma)","DNA methylation class (Heidelberg classifier)","NTRK/ALK/ROS1 fusions (infant gliomas)","TMB / mismatch repair (rare hypermutant, IO-responsive)"],"standardOfCare":[{"setting":"Glioblastoma","approach":"Resection → RT + temozolomide → TTFields; lomustine/bevacizumab at relapse.","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"IDH-mutant grade 2","approach":"Resection → vorasidenib or observation; RT/PCV for high-risk.","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Diagnosis","approach":"MRI with contrast; maximal safe resection with 5-ALA and intraoperative mapping, with early postoperative MRI to measure the extent of resection; integrated histo-molecular diagnosis with methylation classification where available.","refs":[]},{"setting":"Glioblastoma, newly diagnosed","approach":"Radiotherapy 60 Gy in 30 fractions with concurrent and 6 cycles adjuvant temozolomide; from age 65, short-course radiotherapy (40 Gy in 15 fractions) with temozolomide (CCTG CE.6); for older patients unfit for combined treatment, temozolomide alone or hypofractionated radiotherapy alone, chosen by MGMT status (Nordic, NOA-08); TTFields with maintenance temozolomide; trials for MGMT-unmethylated patients.","refs":["temozolomide"]},{"setting":"Glioblastoma, recurrent","approach":"Re-resection or LITT if feasible; lomustine; bevacizumab for oedema/steroid sparing; re-irradiation; clinical trial (CAR-T, FUS-BBB, vaccines) strongly preferred.","refs":[]},{"setting":"IDH-mutant grade 2 glioma","approach":"Maximal resection; vorasidenib for residual/recurrent disease (INDIGO); radiotherapy plus PCV or temozolomide for high-risk or progressive disease.","refs":[]},{"setting":"Oligodendroglioma grade 3 / astrocytoma grade 3","approach":"Radiotherapy plus PCV (RTOG 9402, EORTC 26951) or temozolomide (CATNON).","refs":["temozolomide"]},{"setting":"H3 K27M diffuse midline glioma","approach":"Radiotherapy; dordaviprone at progression (2025); GD2 CAR-T and ONC201 first-line trials.","refs":[]},{"setting":"Paediatric low-grade glioma","approach":"Resection where safe; chemotherapy (carboplatin/vincristine) or tovorafenib / dabrafenib-trametinib for BRAF-altered relapsed disease; avoid radiation in young children.","refs":[]}],"stateOfArt":["Vorasidenib in low-grade glioma.","Methylation-based diagnosis.","TTFields.","Three first-in-class targeted approvals for glioma subtypes in 2024-25: vorasidenib (IDH-mutant), tovorafenib (BRAF paediatric), dordaviprone (H3 K27M).","Molecular classification (WHO 2021, methylation classifier, intraoperative nanopore) now defines diagnosis.","Locoregional CAR-T produces objective responses in recurrent glioblastoma and DIPG, though transient.","Focused ultrasound opens the blood-brain barrier in humans with 4-6x higher drug delivery; efficacy trials underway."],"history":[{"year":1926,"title":"Bailey and Cushing classify gliomas","note":"Histologic classification that lasted, in essence, until 2016.","refs":[]},{"year":1978,"title":"Radiotherapy proven to extend survival (BTSG)","note":"Whole-brain then involved-field radiation becomes standard.","refs":[]},{"year":1999,"title":"Temozolomide approved (anaplastic astrocytoma)","refs":["temozolomide"]},{"year":2005,"title":"Stupp regimen: temozolomide + RT","refs":[]},{"year":2008,"title":"IDH1 mutations discovered in glioma","note":"Parsons/Vogelstein glioblastoma genome sequencing; reclassification follows.","refs":[]},{"year":2009,"title":"Bevacizumab accelerated approval at recurrence","note":"Radiographic response without survival benefit.","refs":[]},{"year":2014,"title":"AVAglio / RTOG 0825: bevacizumab no OS benefit; 5-ALA and methylation classifier emerge","refs":[]},{"year":2015,"title":"TTFields improves OS (EF-14)","refs":[]},{"year":2016,"title":"WHO 2016 integrates molecular markers; ACT IV vaccine fails","refs":[]},{"year":2017,"title":"Short-course radiotherapy plus temozolomide extends survival from age 65 (CCTG CE.6)","refs":[]},{"year":2020,"title":"CheckMate 143: immunotherapy fails at recurrence","note":"CheckMate 548 (2022) and CheckMate 498 (2023) follow in newly diagnosed disease; all three negative.","refs":[]},{"year":2021,"title":"WHO 2021: IDH-wild-type glioblastoma defined molecularly","refs":[]},{"year":2022,"title":"GD2 CAR-T responses in DIPG (Stanford)","refs":[]},{"year":2023,"title":"INDIGO: vorasidenib in grade 2 IDH-mutant glioma; DCVax-L contested publication","refs":[]},{"year":2024,"title":"Vorasidenib approved","refs":[]},{"year":2025,"title":"Dordaviprone approved for H3 K27M diffuse midline glioma","note":"6 August 2025; first systemic therapy for the disease.","refs":[]},{"year":2026,"title":"ASCO 2026: NeoVax personalised vaccine immune responses; multi-target CAR-T; tovorafenib EU approval","refs":[]}],"pipeline":[],"openProblems":["Blood-brain barrier.","Immunologically cold, heterogeneous, infiltrative.","Glioblastoma: no systemic drug has beaten the 2005 standard; getting drugs across the blood-brain barrier is the crux.","Glioblastoma's standard has not changed since 2005: every phase 3 systemic agent since temozolomide has failed, so median survival has not moved in 20 years.","MGMT-unmethylated glioblastoma (~60%) gains almost nothing from chemotherapy and has no approved alternative.","Blood-brain barrier and diffuse infiltration limit delivery and resection; imaging cannot distinguish progression from pseudoprogression reliably.","Immunotherapy failure: low TMB, T-cell exclusion, dexamethasone, and treatment-induced lymphopenia; neoadjuvant approaches are the only signal.","Antigen heterogeneity and loss (EGFRvIII, IL13Rα2) undermine single-target vaccines, ADCs, and CAR-T.","Paediatric tumours (DIPG) have one approved drug with 22% response; durable control remains out of reach.","Trial design: single-arm and external-control comparisons (DCVax-L, historical vaccine data) have repeatedly misled the field."],"route":"/indications/glioblastoma/"}
{"id":"grade-3-net","kind":"indication","name":"Grade 3 well-differentiated neuroendocrine tumour","aka":["NET G3","Grade 3 NET","Well-differentiated grade 3 neuroendocrine tumour","High-grade well-differentiated NET"],"tldr":"Grade 3 well-differentiated neuroendocrine tumours divide fast enough to be called grade 3 yet still look and behave like their slower relatives rather than like neuroendocrine carcinoma. Recognised as separate since 2017, they keep the somatostatin receptor, respond less well to platinum chemotherapy, and in the NETTER-2 trial were among the first treated with lutetium-177 dotatate up front.","summary":"Until 2017 every neuroendocrine neoplasm with a Ki-67 above 20 percent was called neuroendocrine carcinoma and treated like small-cell lung cancer. Pathologists noticed that some of these tumours kept the organoid architecture, uniform nuclei and somatostatin receptor expression of well-differentiated tumours, and that their patients lived far longer than those with carcinoma. Multicentre series, notably Heetfeld and colleagues (2015), showed that these tumours, usually pancreatic and usually with a Ki-67 between 20 and 55 percent, responded poorly to platinum-etoposide but survived longer, and the NORDIC NEC series (2013) had already found that a Ki-67 below 55 percent predicted the same pattern. The WHO classified pancreatic NET G3 as a distinct entity in 2017 and extended it to the whole digestive system in 2019; molecularly these tumours carry the MEN1, DAXX and ATRX changes of neuroendocrine tumours and retain p53 and Rb, whereas carcinoma loses them, which is why p53 and Rb immunohistochemistry is now used when morphology is ambiguous.\n\nTreatment evidence is thin because the entity is new and small. Capecitabine with temozolomide is the most used chemotherapy, on the basis of pancreatic tumour data from E2211 and retrospective grade 3 series, and everolimus and sunitinib are used with less evidence. Somatostatin receptor PET is usually positive, often with FDG avidity as well, and this dual pattern makes radioligand therapy plausible: NETTER-2 (Lancet 2024) was designed to include grade 3 tumours with a Ki-67 up to 55 percent alongside higher grade 2 tumours, and first-line lutetium-177 dotatate lengthened progression-free survival from 8.5 to 22.8 months across the 226 patients, the first randomised evidence in this group. COMPOSE randomises well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic tumours between 177Lu-edotreotide and CAPTEM, everolimus or FOLFOX, and is due to report in 2027.\n\nThe practical decisions are about tempo and receptor status. Tumours near the upper end of Ki-67, growing fast or losing receptor expression on PET are treated more like carcinoma with platinum-etoposide, while receptor-positive tumours with slower tempo are treated like grade 2 tumours with radioligand therapy or CAPTEM. Surgery and liver-directed therapy are used as for other well-differentiated tumours when disease is limited. Whether grade 3 tumours should be graded further, and where the Ki-67 line between tumour and carcinoma really lies, remain open.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"NETTER-2 (Lancet 2024)","url":"https://doi.org/10.1016/S0140-6736(24)00701-3"},{"label":"Heetfeld et al. (Endocrine-Related Cancer 2015)","url":"https://doi.org/10.1530/ERC-15-0119"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":["subtype-page","endocrine"],"related":["lung-net","pancreatic-net","small-intestinal-net","lu-177"],"indications":[],"sections":[],"technologies":["sstr-pet","prrt","pet","radioligand-therapy"],"targets":["sstr2"],"drugs":["lutathera","everolimus","sunitinib","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["net-grade-ki67","prrt-term"],"trials":["nct03972488","nct04919226","compete"],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"A small fraction of neuroendocrine neoplasms, most often pancreatic; recognised as a separate entity by the WHO in 2017 for the pancreas and 2019 for the whole digestive system after series showed it outlives neuroendocrine carcinoma and responds less to platinum.","subtypes":["Grade 3 well-differentiated pancreatic NET (the commonest site)","Grade 3 well-differentiated small intestinal and other gastroenteropancreatic NET","NET G3 with Ki-67 20 to 55 percent, somatostatin receptor-positive (radioligand candidates)","NET G3 with high FDG avidity or falling receptor expression (carcinoma-like behaviour)","Grade 2 to grade 3 progression within a known neuroendocrine tumour"],"biomarkers":["Ki-67 above 20 percent (usually 20 to 55 percent) with well-differentiated morphology","Retained p53 and Rb by immunohistochemistry (abnormal in carcinoma)","Somatostatin receptor PET, usually positive, with FDG PET for dual-tracer assessment","Chromogranin A (monitoring)","MEN1, DAXX and ATRX alterations (tumour lineage, research)","MGMT status (CAPTEM response, investigational)"],"standardOfCare":[{"setting":"Diagnosis","approach":"Morphology, Ki-67 and p53 or Rb immunohistochemistry to separate grade 3 tumour from carcinoma; somatostatin receptor and FDG PET together.","refs":["net-grade-ki67","sstr-pet","pet"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, somatostatin receptor-positive","approach":"Lutetium-177 dotatate first line for Ki-67 up to 55 percent (NETTER-2); somatostatin analogue alongside.","refs":["lutathera","nct03972488","prrt"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, shrinkage needed or receptor-negative","approach":"Capecitabine with temozolomide; everolimus or sunitinib for pancreatic tumours; platinum-etoposide for carcinoma-like tempo or Ki-67 near 55 percent.","refs":["everolimus","sunitinib"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Trials","approach":"COMPOSE: 177Lu-edotreotide against CAPTEM, everolimus or FOLFOX in aggressive grade 2 and grade 3 gastroenteropancreatic tumours.","refs":["nct04919226","itm-11"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Limited disease","approach":"Resection and liver-directed therapy as for other well-differentiated tumours.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}}],"stateOfArt":["The 2017 and 2019 WHO classifications turned a pathology observation into a treatable category and spared these patients platinum they did not benefit from.","NETTER-2 supplied the first randomised evidence in grade 3 tumours and put radioligand therapy first line.","p53 and Rb immunohistochemistry and dual-tracer PET give practical tools for the ambiguous case."],"history":[{"year":2013,"title":"NORDIC NEC: Ki-67 below 55 percent marks a less platinum-sensitive, longer-surviving group","refs":[]},{"year":2015,"title":"Heetfeld and colleagues characterise well-differentiated grade 3 tumours as distinct from carcinoma","refs":[]},{"year":2017,"title":"WHO classification of pancreatic tumours creates NET G3","refs":["net-grade-ki67"]},{"year":2019,"title":"WHO digestive system classification extends NET G3 to the whole gut","refs":["net-grade-ki67"]},{"year":2021,"title":"COMPOSE opens: 177Lu-edotreotide against chemotherapy or everolimus in aggressive grade 2 and grade 3 tumours","refs":["nct04919226","itm-11"]},{"year":2024,"title":"NETTER-2: first-line lutetium-177 dotatate in grade 2 to 3 tumours with Ki-67 up to 55 percent","refs":["nct03972488","lutathera"]}],"pipeline":["nct04919226","itm-11","lutathera","idea-net-dosimetry-prrt"],"openProblems":["The Ki-67 boundary between grade 3 tumour and carcinoma is not sharp, and some cases can only be settled by molecular testing.","No trial has been run in grade 3 tumours alone; NETTER-2 and COMPOSE mix them with grade 2.","Whether platinum-etoposide, CAPTEM or radioligand therapy should come first in the fastest grade 3 tumours is unknown."],"parent":"neuroendocrine","route":"/indications/grade-3-net/"}
{"id":"hcc","kind":"indication","name":"Hepatocellular carcinoma","aka":["Liver Cancer"],"tldr":"Liver cancer almost always grows in a liver already damaged by hepatitis, alcohol or fatty liver disease. It is one of the most preventable cancers, and since 2020 immunotherapy combinations have roughly doubled how long people with advanced disease live.","summary":"Hepatocellular carcinoma is the dominant primary liver cancer (~75-85%) and one of the most preventable: HBV vaccination and HCV cure have cut incidence wherever they were deployed. Its defining feature is that it arises in a diseased organ: chronic hepatitis B, hepatitis C, alcohol-related and metabolic (MASLD) cirrhosis account for most cases, so the liver's remaining function (Child-Pugh, ALBI) matters as much as tumour stage. The BCLC system integrates both and maps each stage to a treatment: ablation, resection or transplantation for early disease; TACE or radioembolisation for intermediate disease; systemic therapy for advanced disease. Surveillance of at-risk patients with six-monthly ultrasound is recommended but poorly adopted, and most patients still present beyond curative stages, which is why it remains the third leading cause of cancer death worldwide.\n\nSystemic therapy changed completely between 2018 and 2026. Sorafenib (SHARP, 2007) was the only option for a decade. Lenvatinib matched it (REFLECT), then IMbrave150 made atezolizumab plus bevacizumab the first regimen to beat sorafenib on survival (OS 19.2 vs 13.4 months). HIMALAYA's STRIDE regimen (single-dose tremelimumab plus durvalumab) followed with a doubling of five-year survival (19.6% vs 9.4%), and CheckMate 9DW's nivolumab plus ipilimumab reached a median OS of 23.7 months (approved 2025). Camrelizumab plus rivoceranib (CARES-310, OS 23.8 vs 15.2 months) is approved in China but has received three FDA complete response letters for manufacturing reasons, most recently in July 2026. Second-line options after sorafenib (regorafenib, cabozantinib, ramucirumab for AFP ≥400) lack data after immunotherapy, the setting most patients now reach.\n\nThe frontier is combining local and systemic therapy. Three phase 3 trials (EMERALD-1, LEAP-012, EMERALD-3) show that adding immunotherapy and anti-VEGF drugs to TACE prolongs progression-free survival by about 30%, but LEAP-012's final overall-survival hazard ratio of 0.98 shows PFS is a weak surrogate here, and adjuvant atezolizumab-bevacizumab (IMbrave050) lost its early benefit with follow-up. Open questions include the right therapy after first-line immunotherapy, the role of immunotherapy before transplantation, GPC3-directed cell therapy, and above all prevention: HBV vaccination and HCV cure could avert most cases, while MASLD-driven HCC in non-cirrhotic livers is rising and escapes surveillance.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hepatocellular_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hepatocellular_carcinoma"}],"tags":["gi","spike"],"related":[],"indications":[],"sections":[],"technologies":["radioembolisation-tare"],"targets":["gpc3","fap"],"drugs":[],"companies":["astrazeneca","bms","merck","bayer","eli-lilly","sirtex","boston-scientific"],"institutions":["mayo-clinic","mskcc"],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"Roughly 900,000 liver cancer cases a year worldwide (GLOBOCAN), ~80% in Asia and Africa, and largely preventable: HBV vaccination and HCV cure have cut incidence in Taiwan, Japan and Egypt. Deaths are ~800,000 a year, and in the United States the death rate has risen faster than for any other cancer over the past two decades, driven by hepatitis C and fatty liver disease.","subtypes":["Viral (HBV, HCV) HCC","Alcohol-related HCC","MASLD/MASH-related HCC (often non-cirrhotic)","Fibrolamellar carcinoma (young adults, DNAJB1-PRKACA fusion)","Combined hepatocellular-cholangiocarcinoma","BCLC stages 0/A, B, C, D"],"biomarkers":["AFP","GPC3 (trials)","Child-Pugh / ALBI liver function","AFP (prognosis; ≥400 ng/mL for ramucirumab)","BCLC stage and performance status","Portal vein tumour thrombus","HBV/HCV status","AFP-L3 and DCP (GALAD score)"],"standardOfCare":[{"setting":"Early","approach":"Resection, ablation, transplant.","refs":[],"guideline":{"version":"NCCN Guidelines: Hepatocellular Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1514"}},{"setting":"Intermediate","approach":"TACE/TARE ± systemic therapy.","refs":["radioligand-therapy"],"guideline":{"version":"NCCN Guidelines: Hepatocellular Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1514"}},{"setting":"Advanced","approach":"Atezolizumab-bevacizumab, durvalumab-tremelimumab, or nivolumab-ipilimumab.","refs":["durvalumab"],"guideline":{"version":"NCCN Guidelines: Hepatocellular Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1514"}},{"setting":"Prevention","approach":"Universal HBV vaccination; antiviral suppression of HBV; direct-acting antiviral cure of HCV; alcohol and metabolic risk reduction.","refs":[],"guideline":{"nccn":"Hepatobiliary Cancers","version":"AASLD 2023 / EASL 2025"}},{"setting":"Surveillance","approach":"Six-monthly ultrasound ± AFP in cirrhosis and high-risk HBV carriers; abbreviated MRI where ultrasound is inadequate.","refs":[],"guideline":{"version":"AASLD 2023 Practice Guidance"}},{"setting":"Very early / early (BCLC 0-A)","approach":"Ablation (RFA/microwave) for ≤3 cm; resection for preserved liver function; transplantation within Milan or downstaged criteria; radiation segmentectomy as an alternative.","refs":["radioembolisation-tare"],"guideline":{"nccn":"Category 1 for resection/ablation/transplant"}},{"setting":"Intermediate (BCLC B)","approach":"TACE (conventional or DEB-TACE) or TARE; systemic therapy for high tumour burden or TACE-refractory disease; TACE + durvalumab-bevacizumab or STRIDE + lenvatinib prolong PFS (OS unproven).","refs":["radioembolisation-tare"],"guideline":{"nccn":"TACE category 1; combinations not yet standard"}},{"setting":"Advanced (BCLC C), first line","approach":"Atezolizumab + bevacizumab (IMbrave150), STRIDE tremelimumab + durvalumab (HIMALAYA), or nivolumab + ipilimumab (CheckMate 9DW); lenvatinib or sorafenib if immunotherapy is contraindicated (transplant, active autoimmune disease).","refs":["durvalumab","sorafenib"],"guideline":{"nccn":"Category 1 (preferred) for all three IO regimens","esmoMcbs":"IMbrave150 grade 5"}},{"setting":"Advanced, second line and beyond","approach":"After immunotherapy: lenvatinib, sorafenib, cabozantinib or regorafenib by extrapolation (no dedicated phase 3); ramucirumab if AFP ≥400 ng/mL; clinical trials.","refs":["cabozantinib"],"guideline":{"nccn":"Category 2A after IO"}},{"setting":"Adjuvant after resection/ablation","approach":"No approved adjuvant therapy; IMbrave050 benefit not sustained. Surveillance imaging every 3-6 months.","refs":[]},{"setting":"Portal vein tumour thrombosis","approach":"Systemic immunotherapy; Y-90 radioembolisation where TACE is contraindicated; radiotherapy to the thrombus in selected patients.","refs":["radioembolisation-tare"]}],"stateOfArt":["IO doublets first line.","GPC3 CAR-T and bispecifics emerging.","Three first-line immunotherapy regimens with overall-survival benefit over sorafenib; median OS approaching two years and five-year survival of one in five with STRIDE.","Choice of regimen is driven by bleeding risk (varices), autoimmune disease and transplant candidacy rather than a predictive biomarker.","Radioembolisation and radiation segmentectomy offer curative-intent options for small tumours and for portal vein thrombosis.","TACE plus systemic therapy prolongs PFS in intermediate-stage disease in three phase 3 trials, but overall survival is unproven (LEAP-012 OS HR 0.98).","Prevention works: HBV vaccination and HCV antivirals have cut incidence in Taiwan, Japan and Egypt; MASLD is the rising cause.","Living-donor transplantation and downstaging widen the pool of curable patients, led by Asian high-volume centres."],"history":[{"year":1941,"title":"Hepatocellular carcinoma linked to cirrhosis in large autopsy series","note":"Establishes the disease-in-a-diseased-organ paradigm.","refs":[]},{"year":1964,"title":"Hepatitis B surface antigen discovered (Blumberg)","note":"Nobel Prize 1976; leads to the vaccine.","refs":[]},{"year":1984,"title":"Taiwan begins universal HBV vaccination","note":"Childhood HCC incidence later falls ~70%.","refs":[]},{"year":1996,"title":"Milan criteria for liver transplantation","note":"Mazzaferro: ~70% five-year survival for small tumours.","refs":[]},{"year":1999,"title":"BCLC staging system published","refs":[]},{"year":2002,"title":"TACE proven to prolong survival (Llovet, Lo)","refs":[]},{"year":2007,"title":"Sorafenib: first systemic therapy","refs":[]},{"year":2007,"title":"SHARP: sorafenib, the first systemic therapy","refs":["sorafenib"]},{"year":2014,"title":"Direct-acting antivirals cure hepatitis C","note":"HCC risk falls ~70% after cure.","refs":[]},{"year":2017,"title":"RESORCE: regorafenib, first second-line benefit; SARAH/SIRveNIB negative for Y-90 vs sorafenib","refs":["sarah-sirvenib"]},{"year":2018,"title":"REFLECT: lenvatinib non-inferior first line; CELESTIAL: cabozantinib second line","refs":[]},{"year":2020,"title":"IMbrave150: atezolizumab-bevacizumab","refs":[]},{"year":2020,"title":"IMbrave150: atezolizumab + bevacizumab beats sorafenib","note":"First regimen to improve OS over sorafenib; new standard.","refs":[]},{"year":2022,"title":"HIMALAYA: STRIDE approved; BCLC update adds systemic therapy for some BCLC-B","refs":[]},{"year":2024,"title":"EMERALD-1 and LEAP-012: TACE + systemic therapy improves PFS; HIMALAYA 5-year OS 19.6%","refs":[]},{"year":2025,"title":"CheckMate 9DW approval (nivolumab + ipilimumab); second FDA CRL for camrelizumab-rivoceranib","refs":[]},{"year":2026,"title":"EMERALD-3 positive for PFS; LEAP-012 final OS HR 0.98; IMbrave050 update negative; third camrelizumab-rivoceranib CRL (23 July)","refs":[]}],"pipeline":["fapi-pet","radioembolisation-tare","gpc3","cabozantinib"],"openProblems":["Liver function limits therapy.","Surveillance uptake in cirrhosis is poor.","No predictive biomarker chooses among the three first-line immunotherapy regimens; PD-L1, TMB and viral aetiology are weak.","Second-line therapy after immunotherapy failure is extrapolated from the sorafenib era; no dedicated phase 3 has read out.","TACE combinations prolong PFS but not (yet) OS; sequencing local and systemic therapy is unresolved.","Adjuvant therapy after curative resection remains unproven; recurrence is ~70% at five years.","Surveillance uptake is below 25% and ultrasound misses early tumours in obese, steatotic livers; MASLD-HCC often arises without cirrhosis.","Immunotherapy in transplant candidates risks rejection; safe washout intervals are undefined.","Child-Pugh B patients are excluded from almost every trial yet make up a large share of real-world patients.","Global inequity: most cases occur in Asia and Africa, where HBV vaccination, HCV treatment and systemic therapy access are uneven."],"route":"/indications/hcc/"}
{"id":"hcc-intermediate","kind":"indication","name":"Intermediate hepatocellular carcinoma (BCLC B)","aka":["Intermediate-stage HCC","Multinodular HCC","TACE-eligible hepatocellular carcinoma","BCLC B"],"tldr":"Intermediate hepatocellular carcinoma is several tumours inside a working liver, too many to cut out but with no spread beyond it. The standard treatment for two decades has been chemoembolisation through the hepatic artery, and trials now show that adding immunotherapy and anti-angiogenic drugs to it delays progression.","summary":"BCLC stage B covers multinodular hepatocellular carcinoma with preserved liver function, no cancer-related symptoms and no macrovascular invasion or extrahepatic spread. The 2022 BCLC update split it into three groups: patients whose tumour burden allows downstaging or extended transplant criteria, those with well-defined nodules suited to transarterial chemoembolisation, and those with diffuse, infiltrative or bilobar disease who do better moving straight to systemic therapy, a change described as treatment stage migration.\n\nTransarterial chemoembolisation delivers chemotherapy-loaded particles or drug-eluting beads into the arteries feeding the tumours and blocks them; two randomised trials in 2002 (Llovet in Barcelona and Lo in Hong Kong) showed it prolongs survival, and it has been the standard since. Radioembolisation with yttrium-90 microspheres is an alternative with fewer post-procedure symptoms, though phase 3 trials against sorafenib in more advanced disease were negative. Repeated embolisation damages the liver, so the ART and other scores guide when to stop and switch.\n\nTwo phase 3 trials published in the Lancet in 2025 added systemic therapy to chemoembolisation: EMERALD-1 combined durvalumab and bevacizumab with TACE and extended median progression-free survival from 8.2 to 15.0 months, and LEAP-012 combined lenvatinib and pembrolizumab with TACE and extended it from 10.0 to 14.6 months; overall survival was immature in both at first analysis. EMERALD-3, testing durvalumab and tremelimumab with TACE, reported a benefit in 2026. The atezolizumab-bevacizumab and other advanced-stage regimens are also used directly in patients with high tumour burden, and ongoing trials compare systemic therapy alone with the combinations.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization","links":[{"label":"EMERALD-1 (Lancet 2025)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02551-0/abstract"},{"label":"LEAP-012 (Lancet 2025)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract"},{"label":"BCLC 2022 update (J Hepatol)","url":"https://pubmed.ncbi.nlm.nih.gov/34801630/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Transcatheter_arterial_chemoembolization"}],"tags":["subtype-page"],"related":["y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"Multiple tumours confined to a liver that still functions, without vein invasion or spread; the most heterogeneous BCLC stage, for which the 2022 update expects a median survival above two and a half years with chemoembolisation and now systemic therapy.","subtypes":["Multinodular HCC in a cirrhotic liver within the up-to-seven criteria (downstaging or extended transplant)","Well-defined nodules suitable for TACE","Diffuse or infiltrative bilobar HCC (systemic therapy first)","TACE-refractory HCC","BCLC B treated with TACE plus systemic therapy (EMERALD-1, LEAP-012)"],"biomarkers":["Tumour number and size (up-to-seven and other burden criteria)","Child-Pugh and ALBI liver function before and after each embolisation","Alpha-fetoprotein response","Modified RECIST response on contrast imaging","Absence of macrovascular invasion and extrahepatic spread (defines the stage)"],"standardOfCare":[{"setting":"Well-defined nodules, preserved liver function","approach":"Transarterial chemoembolisation, conventional or with drug-eluting beads, repeated on demand; radioembolisation as an alternative.","refs":["radioembolisation-tare"]},{"setting":"TACE plus systemic therapy","approach":"Durvalumab with bevacizumab (EMERALD-1) or lenvatinib with pembrolizumab (LEAP-012) added to TACE, where approved; durvalumab-tremelimumab with TACE after EMERALD-3.","refs":["durvalumab","pembrolizumab"]},{"setting":"High burden or diffuse disease","approach":"Systemic therapy as for advanced disease (atezolizumab-bevacizumab or durvalumab-tremelimumab) instead of embolisation.","refs":["durvalumab"]},{"setting":"Within transplant criteria after downstaging","approach":"Chemoembolisation or radioembolisation as a bridge, then liver transplantation.","refs":[]}],"stateOfArt":["Chemoembolisation remains the backbone, but the 2022 BCLC update sends patients with diffuse or high-burden disease straight to systemic therapy.","EMERALD-1 and LEAP-012 are the first phase 3 trials to improve on TACE alone in twenty years.","Whether the combinations lengthen life, not just time to progression, is still awaited."],"history":[{"year":2002,"title":"Llovet and Lo randomised trials: chemoembolisation prolongs survival","refs":[]},{"year":2010,"title":"Drug-eluting bead TACE (PRECISION V) matches conventional TACE with less toxicity","refs":[]},{"year":2022,"title":"BCLC update subdivides intermediate stage and introduces treatment stage migration","refs":[]},{"year":2025,"title":"EMERALD-1 and LEAP-012: systemic therapy plus TACE delays progression","refs":[]},{"year":2026,"title":"EMERALD-3: durvalumab-tremelimumab plus TACE reported positive","refs":[]}],"pipeline":["radioembolisation-tare","durvalumab"],"openProblems":["No overall survival gain yet shown for TACE combinations.","Which patients should skip embolisation and go straight to systemic therapy.","Liver damage from repeated embolisation limits later treatment options."],"parent":"hcc","route":"/indications/hcc-intermediate/"}
{"id":"hereditary-ppgl","kind":"indication","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","aka":["Familial paraganglioma syndromes","SDHB-related paraganglioma","SDHD-related head and neck paraganglioma","VHL-associated pheochromocytoma","MEN2-associated pheochromocytoma","Hereditary PPGL"],"tldr":"Hereditary pheochromocytoma and paraganglioma is the inherited form of these adrenaline-producing tumours, caused by a fault in one of more than a dozen genes, most often SDHB, SDHD, VHL and RET. Knowing the gene changes care: SDHB carriers have the highest risk of spread, VHL and MEN2 patients get adrenal-sparing surgery because tumours arise on both sides, and relatives are screened.","summary":"Pheochromocytomas (adrenal) and paragangliomas (sympathetic chain, head and neck) have the strongest hereditary basis of any tumour type: germline mutations are found in 30 to 40 percent of patients, in the succinate dehydrogenase genes (SDHB, SDHD, SDHC, SDHA and SDHAF2), VHL, RET (MEN2), NF1, MAX, TMEM127, FH and others, and the Endocrine Society guideline recommends that all patients be offered testing. The genes fall into two clusters that shape the tumour: cluster 1 (SDHx, VHL, FH, EPAS1) tumours are pseudohypoxic, noradrenergic or non-secreting, often extra-adrenal and multiple, and express somatostatin receptors strongly; cluster 2 (RET, NF1, MAX, TMEM127) tumours are kinase-driven, adrenergic and usually adrenal. SDHB mutations carry the highest risk of metastasis, SDHD (paternally inherited) causes multiple head and neck paragangliomas, VHL and MEN2 cause bilateral pheochromocytomas alongside their other tumours, and SDHx carriers are also at risk of gastrointestinal stromal tumours, renal cell carcinoma and pituitary adenomas.\n\nManagement differs from sporadic disease at every step. Diagnosis rests on plasma or urinary metanephrines and, for non-secreting head and neck tumours, imaging; SDHB immunohistochemistry on the tumour flags an SDHx mutation, and 68Ga-DOTATATE PET is the preferred whole-body scan for cluster 1 disease because of its somatostatin receptor expression. Surgery follows alpha-blockade, and in VHL and MEN2 a cortical-sparing adrenalectomy is preferred to avoid lifelong steroid dependence after bilateral tumours; head and neck paragangliomas, which rarely secrete and grow slowly, are often watched or irradiated rather than resected because surgery risks the cranial nerves. Carriers enter lifelong surveillance with annual metanephrines and periodic whole-body MRI from childhood in SDHB and SDHD families, and cascade testing is offered to relatives. For carriers who develop advanced disease, the HIF-2 alpha inhibitor belzutifan, approved for VHL-associated tumours in 2021 and for advanced pheochromocytoma and paraganglioma in 2025, exploits the pseudohypoxia pathway directly, and radioligand therapy with lutetium-177 dotatate suits the somatostatin-receptor-rich cluster 1 tumours. The genetics also guide prognosis: metastatic risk, multiplicity and the chance of a second primary all follow the gene.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Paraganglioma","links":[{"label":"Endocrine Society PPGL guideline 2014","url":"https://doi.org/10.1210/jc.2014-1498"},{"label":"Belzutifan in VHL (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2103425"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Paraganglioma"}],"tags":["subtype-page","endocrine"],"related":["metastatic-ppgl","pheochromocytoma-paraganglioma","ga-68","lu-177"],"indications":[],"sections":[],"technologies":["sstr-pet","radioligand-therapy","prrt","ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["sdh-deficiency"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"Up to four in ten pheochromocytomas and paragangliomas are caused by a germline mutation, the highest proportion of any cancer, so every patient is offered genetic testing; carriers face lifelong surveillance for new tumours.","subtypes":["SDHB-related paraganglioma (highest metastatic risk; extra-adrenal, abdominal and thoracic)","SDHD-related head and neck paraganglioma (multiple, paternal inheritance, rarely secreting)","SDHC, SDHA and SDHAF2-related paraganglioma (rarer, lower penetrance)","VHL-associated pheochromocytoma (bilateral, noradrenergic; belzutifan eligible)","MEN2 (RET)-associated pheochromocytoma (bilateral, adrenergic; with medullary thyroid cancer)","NF1, MAX and TMEM127-associated pheochromocytoma (adrenal, later onset)","Carney triad and Carney-Stratakis dyad (paraganglioma with gastrointestinal stromal tumour)"],"biomarkers":["Germline panel testing (SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, NF1, MAX, TMEM127, FH, EPAS1)","Plasma free or urinary fractionated metanephrines (noradrenergic pattern in cluster 1)","SDHB immunohistochemistry (loss indicates any SDHx mutation)","68Ga-DOTATATE PET (somatostatin receptor expression, staging and radioligand eligibility)","Tumour size, extra-adrenal site and SDHB status as metastatic risk factors","Surveillance whole-body MRI in carriers"],"standardOfCare":[{"setting":"Genetic diagnosis","approach":"Germline panel testing offered to every patient; SDHB immunohistochemistry on tumour tissue; cascade testing of relatives with genetic counselling.","refs":["sdh-deficiency"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Biochemical and imaging work-up","approach":"Plasma or urinary metanephrines; CT or MRI; 68Ga-DOTATATE PET as the preferred functional scan for SDHx and other cluster 1 disease.","refs":["sstr-pet","ct"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Adrenal tumours in VHL and MEN2","approach":"Alpha-blockade then cortical-sparing (partial) adrenalectomy to preserve adrenal function given the risk of bilateral disease.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Head and neck paragangliomas","approach":"Observation for small asymptomatic tumours; surgery or fractionated or stereotactic radiotherapy when growing or symptomatic, weighing cranial nerve risk.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Surveillance of carriers","approach":"Annual metanephrines and clinical review from childhood, with whole-body MRI every two to three years in SDHB and SDHD carriers; screening for associated tumours (GIST, renal cell carcinoma, pituitary).","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Advanced disease in carriers","approach":"Belzutifan (approved for VHL-associated tumours 2021 and for advanced pheochromocytoma and paraganglioma 2025); lutetium-177 dotatate for somatostatin-receptor-positive disease; see the metastatic record.","refs":["lutathera","prrt"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}}],"stateOfArt":["Universal germline testing and gene-based surveillance find tumours before they cause harm.","The cluster 1 and cluster 2 framework links gene, biochemistry, imaging and therapy.","Belzutifan is the first drug aimed at the pseudohypoxia pathway that drives cluster 1 tumours."],"history":[{"year":1993,"title":"RET mutations identified in MEN2; VHL gene cloned","refs":[]},{"year":2000,"title":"SDHD mutations found in familial head and neck paraganglioma; SDHB follows in 2001","refs":["sdh-deficiency"]},{"year":2014,"title":"Endocrine Society guideline recommends germline testing for all patients","refs":[]},{"year":2017,"title":"TCGA analysis defines the pseudohypoxia and kinase clusters","refs":[]},{"year":2021,"title":"Belzutifan approved for VHL-associated tumours","refs":[]},{"year":2025,"title":"Belzutifan approved for advanced pheochromocytoma and paraganglioma","refs":[]}],"pipeline":["lutathera","prrt"],"openProblems":["Penetrance of SDHx mutations is incomplete and variable, so how intensively to screen carriers is debated.","No treatment prevents new tumours in carriers.","Whether belzutifan works in SDHx-related as well as VHL-related disease needs more data.","Head and neck paragangliomas have no effective medical therapy."],"parent":"pheochromocytoma-paraganglioma","route":"/indications/hereditary-ppgl/"}
{"id":"lung-net","kind":"indication","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","aka":["Bronchial carcinoid","Pulmonary carcinoid","Typical carcinoid","Atypical carcinoid","Lung NET","Bronchopulmonary neuroendocrine tumour"],"tldr":"Lung neuroendocrine tumours, called typical and atypical carcinoids, are slow-growing tumours of the airways that are usually cured by surgery. When they spread, everolimus is the one drug tested in a randomised trial for this site, cabozantinib was approved in 2025, and somatostatin analogues and lutetium radioligand therapy are borrowed from gut tumours.","summary":"Lung neuroendocrine tumours are graded differently from their gut counterparts: the WHO lung classification separates typical carcinoid (fewer than two mitoses per two square millimetres and no necrosis) from atypical carcinoid (two to ten mitoses or foci of necrosis), with Ki-67 used to support the count rather than define it, and places both alongside small-cell and large-cell neuroendocrine carcinoma in a single neuroendocrine group. Most typical carcinoids sit centrally in a main or lobar bronchus and present with cough, wheeze, haemoptysis or recurrent pneumonia behind an obstructed airway; peripheral tumours are found incidentally. A few produce ectopic ACTH and Cushing's syndrome, carcinoid syndrome is uncommon without liver metastases, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is a rare precursor that seeds multiple tumourlets. About a twentieth arise in patients with MEN1.\n\nSurgery is the treatment for localised disease and usually the cure: lobectomy or a parenchyma-sparing sleeve resection with systematic nodal dissection, with endobronchial resection reserved for patients who cannot tolerate an operation. Adjuvant therapy has no proven benefit and follow-up is prolonged because atypical carcinoids can recur years later. For advanced disease the evidence is thin. RADIANT-4 (Lancet 2016) is the only randomised trial to include lung tumours in numbers: 302 patients with non-functional lung or gastrointestinal neuroendocrine tumours were randomised to everolimus or placebo and progression-free survival lengthened from 3.9 to 11.0 months, and the FDA approved everolimus for lung neuroendocrine tumours in 2016. The phase 2 LUNA trial (2017) tested pasireotide, everolimus and the combination in lung and thymic tumours and found each active, without a randomised comparison against placebo.\n\nThe rest of the sequence is borrowed. Somatostatin analogues are used for somatostatin receptor-positive tumours on the strength of gut trials and the small SPINET study of lanreotide, and lutetium-177 dotatate is given off-label to receptor-positive lung tumours on series data, since NETTER-1 and NETTER-2 enrolled only gastroenteropancreatic disease. CABINET (New England Journal of Medicine 2024) included lung and thymic tumours in its extra-pancreatic cohort, where cabozantinib lengthened progression-free survival from 3.9 to 8.4 months, and a subgroup analysis presented in 2025 showed a large reduction in progression risk in the lung and thymic tumours; cabozantinib's 2025 approval covers them. Temozolomide-based chemotherapy is used for atypical carcinoids that need shrinkage, and platinum-etoposide is reserved for tumours behaving like carcinoma.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"RADIANT-4 (Lancet 2016)","url":"https://doi.org/10.1016/S0140-6736(15)00817-X"},{"label":"CABINET (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2403991"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":["subtype-page","endocrine","lung"],"related":["grade-3-net","pancreatic-net","small-intestinal-net","lu-177"],"indications":[],"sections":[],"technologies":["sstr-pet","prrt","ct"],"targets":["sstr2"],"drugs":["everolimus","cabozantinib","lutathera","ga68-dotatate","pasireotide"],"companies":[],"institutions":[],"pathways":[],"terms":["net-grade-ki67"],"trials":["radiant-3-4","cabinet","nct03972488"],"people":[],"bottlenecks":[],"keyPapers":["paper-cabinet-cabozantinib-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"group":"lung","burden":"A small minority of lung cancers, occurring in younger patients and non-smokers more often than other lung cancers; typical carcinoids are usually cured by surgery, atypical carcinoids recur more often.","subtypes":["Typical carcinoid of the central bronchus (low mitotic count, no necrosis)","Atypical carcinoid (two to ten mitoses or necrosis, higher recurrence)","Peripheral lung neuroendocrine tumour (incidental, sometimes multiple)","Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) with tumourlets","Lung carcinoid with ectopic ACTH and Cushing's syndrome","MEN1-associated lung neuroendocrine tumour","Thymic neuroendocrine tumour (grouped with lung in trials)"],"biomarkers":["Mitotic count and necrosis (WHO typical versus atypical)","Ki-67 index (supportive, not definitional in the lung)","Somatostatin receptor PET (staging and somatostatin analogue or radioligand eligibility)","Chromogranin A (monitoring)","ACTH and cortisol where Cushing's syndrome is suspected","Germline MEN1 in young or multiple tumours"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Bronchoscopy with biopsy for central tumours, CT of the chest and abdomen, somatostatin receptor PET, and pathology graded by mitotic count and necrosis.","refs":["ct","sstr-pet","ga68-dotatate","net-grade-ki67"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Localised disease","approach":"Lobectomy or sleeve resection with systematic nodal dissection; endobronchial resection for patients unfit for surgery; no adjuvant therapy.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, somatostatin receptor-positive, slow tempo","approach":"Octreotide or lanreotide, by extrapolation from gut trials and the SPINET study.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, progressive","approach":"Everolimus (RADIANT-4); cabozantinib (CABINET); lutetium-177 dotatate off-label for receptor-positive tumours; temozolomide-based chemotherapy for atypical carcinoids needing shrinkage.","refs":["everolimus","radiant-3-4","cabozantinib","cabinet","lutathera","prrt"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Hormone syndromes","approach":"Somatostatin analogues for carcinoid syndrome; steroidogenesis inhibitors or resection for ectopic ACTH.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}}],"stateOfArt":["Surgery cures most typical carcinoids, and parenchyma-sparing sleeve resection preserves lung function.","Everolimus is the only drug with randomised evidence specific to lung neuroendocrine tumours, and cabozantinib joined it in 2025 through the CABINET extra-pancreatic cohort.","The lung classification by mitotic count and necrosis, rather than Ki-67, still governs treatment, and the two systems are being reconciled."],"history":[{"year":1972,"title":"Arrigoni defines atypical carcinoid as a separate entity","refs":[]},{"year":2015,"title":"WHO lung classification groups carcinoids with small-cell and large-cell neuroendocrine carcinoma as neuroendocrine tumours","refs":["net-grade-ki67"]},{"year":2016,"title":"RADIANT-4: everolimus approved for lung neuroendocrine tumours","refs":["radiant-3-4","everolimus"]},{"year":2017,"title":"LUNA: pasireotide and everolimus active in lung and thymic tumours","refs":[]},{"year":2024,"title":"CABINET published with lung and thymic tumours in the extra-pancreatic cohort","refs":["cabinet"]},{"year":2025,"title":"Cabozantinib approved for previously treated neuroendocrine tumours including lung; ESMO subgroup analysis","refs":["cabozantinib","cabinet"]}],"pipeline":["cabinet","prrt","sstr-pet"],"openProblems":["No randomised trial has tested somatostatin analogues or radioligand therapy specifically in lung neuroendocrine tumours.","Lung and gastroenteropancreatic grading systems disagree, so trial eligibility and guideline advice do not map cleanly.","Atypical carcinoids relapse late and there is no proven adjuvant therapy."],"parent":"neuroendocrine","route":"/indications/lung-net/"}
{"id":"meningioma","kind":"indication","name":"Meningioma","aka":["Meningeal tumour","Atypical meningioma","Anaplastic meningioma","Malignant meningioma"],"tldr":"Meningiomas grow from the membranes covering the brain and spinal cord rather than from the brain itself. Most are slow and benign and are either watched or removed; radiotherapy or radiosurgery treats what surgery cannot reach or what grows back, and no drug has yet been approved for them.","summary":"Meningiomas arise from arachnoid cap cells and are graded 1 to 3 in WHO 2021 by mitotic count, brain invasion and specific histological patterns, with two molecular criteria that assign grade 3 regardless of appearance: homozygous CDKN2A/B deletion and TERT promoter mutation. About half of sporadic tumours carry NF2 loss with monosomy 22, and most of the rest carry mutually exclusive mutations in TRAF7, KLF4, AKT1, SMO, PIK3CA or POLR2A that cluster at the skull base (Clark and Brastianos, 2013). DNA methylation classes and integrated molecular grading (Sahm 2017, Nassiri 2021) predict recurrence better than histology alone. Radiation exposure is the only established environmental cause; progesterone and oestrogen receptors explain the female excess and the link to some progestogens.\n\nIncidental small meningiomas are watched with MRI. Symptomatic or growing tumours are resected, with completeness graded by the Simpson scale, and complete resection of a grade 1 tumour is usually curative. Radiosurgery controls most small tumours (under about 3 cm) and is the usual choice for skull base and cavernous sinus lesions that cannot be safely removed. Fractionated radiotherapy is given after incomplete resection of grade 2 tumours and after any resection of grade 3 tumours, following the phase 2 EORTC 22042-26042 and RTOG 0539 studies; whether completely resected grade 2 tumours need radiotherapy is the question of the ROAM/EORTC 1308 and NRG BN003 randomised trials. Proton therapy is used for large skull base and re-irradiation cases.\n\nNo systemic therapy is approved. Hydroxyurea, somatostatin analogues, interferon and mifepristone have all failed or shown marginal activity; bevacizumab and sunitinib produce modest control in recurrent high-grade disease, everolimus with octreotide has phase 2 activity (CEVOREM), and Alliance A071401 is testing mutation-matched drugs (the FAK inhibitor GSK2256098 in NF2-mutant tumours, SMO and AKT inhibitors, CDK inhibitors). Somatostatin receptor 2 expression makes DOTATATE PET useful for imaging and has led to trials of peptide receptor radionuclide therapy. Grade 3 and recurrent unresectable meningiomas remain a real unmet need.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Meningioma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Meningioma"},{"label":"EANO guideline on meningiomas (Neuro-Oncology 2021)","url":"https://doi.org/10.1093/neuonc/noab150"}],"tags":["subtype-page","cns"],"related":["glioblastoma"],"indications":[],"sections":[],"technologies":["prrt"],"targets":[],"drugs":["sunitinib","everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"central nervous system","burden":"The commonest primary intracranial tumour, found in about one in a hundred adults on imaging, mostly women; the great majority are grade 1 and never threaten life, while grade 3 tumours behave like cancers and have no approved drug.","subtypes":["Meningioma, grade 1 (meningothelial, fibrous, transitional, psammomatous and other benign patterns)","Meningioma, grade 2 (atypical; chordoid and clear cell patterns)","Meningioma, grade 3 (anaplastic; or any meningioma with CDKN2A/B homozygous deletion or TERT promoter mutation)","NF2-related meningioma (multiple, often with schwannoma)","Skull base meningioma with TRAF7, KLF4, AKT1, SMO or PIK3CA mutation (convexity tumours are mostly NF2-driven)","Spinal meningioma (intradural extramedullary)"],"biomarkers":["WHO grade with mitotic count and brain invasion","CDKN2A/B homozygous deletion and TERT promoter mutation (assign grade 3)","NF2 loss and monosomy 22","TRAF7, KLF4, AKT1, SMO, PIK3CA and POLR2A mutations","DNA methylation class and integrated molecular grade","Somatostatin receptor 2 expression (DOTATATE PET)","Simpson grade of resection"],"standardOfCare":[{"setting":"Incidental or small asymptomatic","approach":"Observation with serial MRI; many never grow. Treatment when growth or symptoms appear.","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Symptomatic or growing, accessible","approach":"Surgical resection as complete as safely possible; complete resection of a grade 1 tumour is usually curative and needs no adjuvant treatment.","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Small, skull base or surgically inaccessible","approach":"Stereotactic radiosurgery (Gamma Knife, CyberKnife or linac) or fractionated stereotactic radiotherapy, with high long-term control rates for grade 1 tumours.","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Grade 2, incompletely resected, and all grade 3","approach":"Fractionated radiotherapy after surgery (EORTC 22042-26042, RTOG 0539); proton therapy for large or re-irradiated skull base tumours; observation versus radiotherapy after complete resection of grade 2 tumours is under trial (ROAM/EORTC 1308, NRG BN003).","refs":[],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Recurrent, no surgical or radiotherapy option","approach":"No approved drug. Bevacizumab, sunitinib or everolimus with a somatostatin analogue on phase 2 evidence; mutation-matched trials (Alliance A071401) and peptide receptor radionuclide therapy studies preferred.","refs":["sunitinib","everolimus","prrt"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}}],"stateOfArt":["Two molecular markers now assign grade 3 regardless of histology, and methylation classes forecast recurrence better than the microscope.","Radiosurgery controls most small meningiomas without an operation and has become the default for skull base disease.","Meningioma is the commonest brain tumour and still has no approved systemic therapy; mutation-matched and radionuclide trials are the first rational attempts."],"history":[{"year":1922,"title":"Cushing coins the term meningioma","note":"Cushing and Eisenhardt's 1938 monograph followed, with the first large surgical series.","refs":[]},{"year":1957,"title":"Simpson grades completeness of resection and links it to recurrence","refs":[]},{"year":1993,"title":"NF2 gene identified on chromosome 22","note":"Trofatter and Rouleau clone the gene whose loss drives most meningiomas and schwannomas.","refs":[]},{"year":2013,"title":"Exome sequencing finds TRAF7, KLF4, AKT1 and SMO mutations in NF2-intact meningiomas","note":"Clark and colleagues (Science) and Brastianos and colleagues (Nature Genetics).","refs":[]},{"year":2017,"title":"DNA methylation classes of meningioma predict recurrence","note":"Sahm and colleagues (Lancet Oncology).","refs":[]},{"year":2021,"title":"WHO 2021 adds CDKN2A/B deletion and TERT promoter mutation as grade 3 criteria","refs":[]}],"pipeline":["prrt","everolimus"],"openProblems":["No approved systemic therapy; grade 3 and recurrent unresectable tumours have few options.","Whether completely resected grade 2 meningiomas need radiotherapy (ROAM, NRG BN003).","Which incidental meningiomas will grow; most never do.","Long-term cognitive and endocrine effects of radiotherapy to the skull base."],"route":"/indications/meningioma/"}
{"id":"metastatic-ppgl","kind":"indication","name":"Metastatic pheochromocytoma and paraganglioma","aka":["Malignant pheochromocytoma","Metastatic paraganglioma","Advanced PPGL","Unresectable pheochromocytoma and paraganglioma"],"tldr":"Metastatic pheochromocytoma and paraganglioma is disease that has spread to bone, lymph nodes, liver or lungs, the only way these adrenaline-producing tumours are called malignant. It is often slow, so treatment starts with blood pressure control and watching, then moves through radioactive drugs that home to the tumour, the kinase inhibitor sunitinib, chemotherapy and, since 2025, belzutifan.","summary":"No pathological feature reliably separates benign from malignant pheochromocytoma and paraganglioma; malignancy is defined by metastases at sites where chromaffin tissue does not normally occur, above all bone, lymph nodes, liver and lung. Metastatic disease occurs in about a tenth of adrenal tumours and a much larger share of extra-adrenal sympathetic paragangliomas, and SDHB mutation, large size, extra-adrenal site and a noradrenergic or dopaminergic profile are the main risk factors. The course is heterogeneous: some patients live for decades with stable bone metastases, others progress within months, so the first decision is whether to treat at all. Catecholamine excess is controlled throughout with alpha-blockade (phenoxybenzamine or doxazosin) and beta-blockade added second, with metyrosine for refractory cases, and any procedure, including biopsy and embolisation, is done under blockade to avoid a hypertensive crisis. Somatostatin receptor PET (68Ga-DOTATATE) and 123I-MIBG scintigraphy stage the disease and, by showing uptake, select patients for the corresponding radionuclide therapy.\n\nTreatment is sequenced by pace. Indolent disease is watched or treated locally with surgery, radiotherapy, ablation or embolisation of dominant lesions. For progressive disease, radionuclide therapy is the first systemic step: high-specific-activity 131I-MIBG (iobenguane, Azedra) was approved in 2018 after a phase 2 trial in which a quarter of patients halved their antihypertensive medication and about a fifth had tumour responses, though the manufacturer withdrew it from the market in 2024, and lutetium-177 dotatate, approved for gastroenteropancreatic neuroendocrine tumours, is used for somatostatin-receptor-positive disease on the strength of retrospective series and phase 2 trials. Sunitinib is the one systemic drug with randomised evidence: FIRSTMAPPP (Lancet 2024), an academic phase 2 trial that took twelve years to enrol 78 patients, showed 12-month progression-free survival of 36 percent against 19 percent on placebo. Cyclophosphamide, vincristine and dacarbazine (CVD) chemotherapy, in use since 1988, and temozolomide, which is active particularly in SDHB-mutant tumours, are the cytotoxic options, and cabozantinib showed activity in the phase 2 NATALIE trial. Belzutifan, the HIF-2 alpha inhibitor, was approved in the United States in May 2025 for adults and children over 12 with locally advanced, unresectable or metastatic disease after a response rate of 26 percent in the LITESPARK-015 cohort, the first approval for the disease in seven years and the first to exploit the pseudohypoxia biology of cluster 1 tumours; the imipridone ONC206 and radioligand combinations are in trials. Bone metastases, the commonest site, are treated with denosumab or bisphosphonates and palliative radiotherapy.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Pheochromocytoma","links":[{"label":"FIRSTMAPPP (Lancet 2024)","url":"https://doi.org/10.1016/S0140-6736(23)02554-0"},{"label":"Endocrine Society PPGL guideline 2014","url":"https://doi.org/10.1210/jc.2014-1498"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pheochromocytoma"}],"tags":["subtype-page","endocrine"],"related":["hereditary-ppgl","pheochromocytoma-paraganglioma","small-intestinal-net","ga-68","i-123","lu-177","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","prrt","mibg-theranostics","sstr-pet","fdg-pet"],"targets":["sstr2"],"drugs":["sunitinib","cabozantinib","lutathera","i131-mibg","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["sdh-deficiency"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"About one in ten pheochromocytomas and up to a third or more of sympathetic paragangliomas, especially SDHB-related ones, metastasise to bone, lymph nodes, liver and lung; the course ranges from indolent over decades to rapidly fatal.","subtypes":["Indolent metastatic pheochromocytoma or paraganglioma (bone-predominant, observation or local therapy)","Progressive somatostatin-receptor-positive metastatic paraganglioma (lutetium-177 dotatate)","MIBG-avid metastatic pheochromocytoma (131I-MIBG where available)","SDHB-related metastatic paraganglioma (temozolomide-sensitive, belzutifan candidate)","Rapidly progressive metastatic pheochromocytoma or paraganglioma (CVD chemotherapy)","Metastatic pheochromocytoma or paraganglioma with uncontrolled catecholamine excess"],"biomarkers":["Plasma or urinary metanephrines and 3-methoxytyramine (secretory profile, monitoring)","Germline and somatic SDHB, VHL and other cluster status (prognosis, belzutifan and temozolomide sensitivity)","68Ga-DOTATATE PET uptake (lutetium-177 dotatate eligibility)","123I-MIBG uptake (131I-MIBG eligibility)","Rate of progression on serial imaging (decides when to treat)","Bone scan or FDG-PET for skeletal disease"],"standardOfCare":[{"setting":"All patients","approach":"Alpha-blockade with beta-blockade added second; metyrosine for refractory symptoms; blockade before every procedure; bone-protective agents for skeletal metastases.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Staging","approach":"68Ga-DOTATATE PET, 123I-MIBG scintigraphy where 131I-MIBG is available, CT or MRI, FDG-PET for SDHB-related disease; germline testing.","refs":["sstr-pet","mibg-theranostics","fdg-pet"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Indolent disease","approach":"Active surveillance; resection, radiotherapy, thermal ablation or embolisation of dominant or symptomatic lesions.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Progressive disease, radionuclide therapy","approach":"Lutetium-177 dotatate for somatostatin-receptor-positive disease; 131I-MIBG for MIBG-avid disease where still available (approved 2018, withdrawn from market 2024).","refs":["lutathera","prrt","radioligand-therapy","i131-mibg","mibg-theranostics"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Progressive disease, systemic drugs","approach":"Belzutifan (approved 2025); sunitinib (FIRSTMAPPP); cabozantinib; cyclophosphamide, vincristine and dacarbazine or temozolomide for rapidly progressive or SDHB-related disease.","refs":["sunitinib","cabozantinib","temozolomide"],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Trials","approach":"ONC206, radioligand combinations and next-generation HIF-2 alpha inhibitors.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}}],"stateOfArt":["Belzutifan is the first approved targeted drug and the first to act on the tumour's own hypoxia biology.","FIRSTMAPPP proved that randomised trials are possible in this ultra-rare disease and validated sunitinib.","Radionuclide therapy gives durable control to patients whose tumours take up the tracer."],"history":[{"year":1988,"title":"Cyclophosphamide, vincristine and dacarbazine chemotherapy reported at the NIH","refs":[]},{"year":1991,"title":"131I-MIBG therapy in malignant pheochromocytoma reported","refs":["i131-mibg","mibg-theranostics"]},{"year":2018,"title":"High-specific-activity 131I-MIBG (Azedra) approved in the United States","refs":["i131-mibg"]},{"year":2024,"title":"FIRSTMAPPP: sunitinib improves progression-free survival; Azedra withdrawn from the market","refs":["sunitinib","i131-mibg"]},{"year":2025,"title":"Belzutifan approved for advanced pheochromocytoma and paraganglioma","refs":[]}],"pipeline":["lutathera","prrt","sunitinib","cabozantinib"],"openProblems":["No randomised trial has compared radionuclide therapy with drugs or defined their order.","Azedra's withdrawal leaves MIBG-avid, somatostatin-receptor-negative patients without a radionuclide option in many countries.","Catecholamine crises during treatment remain dangerous.","The disease is too rare and too slow for conventional trial designs."],"parent":"pheochromocytoma-paraganglioma","route":"/indications/metastatic-ppgl/"}
{"id":"multiple-endocrine-neoplasia","kind":"indication","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","aka":["MEN1","MEN2A","MEN2B","MEN4","Wermer syndrome","Sipple syndrome"],"tldr":"The MEN syndromes are inherited faults in a single gene that cause tumours in several hormone glands over a lifetime. Because the gene can be found in childhood, at-risk relatives can be tested, watched and in MEN2 have the thyroid removed before cancer develops; and for MEN2 thyroid cancer that does spread there is now a precise pill, selpercatinib, that blocks the faulty RET protein.","summary":"MEN1 is caused by germline loss-of-function mutations in MEN1, encoding the tumour suppressor menin, and produces parathyroid hyperplasia (nearly universal), duodenopancreatic neuroendocrine tumours (gastrinoma, insulinoma, non-functioning PanNETs, the main cause of death), anterior pituitary tumours, and adrenal, thymic and bronchial neuroendocrine tumours. MEN2 is caused by germline activating mutations in the RET receptor tyrosine kinase: MEN2A (codon 634 most often) causes medullary thyroid carcinoma (MTC), pheochromocytoma and parathyroid disease; MEN2B (M918T) causes early aggressive MTC, pheochromocytoma, mucosal neuromas and a marfanoid habitus. MEN4 (CDKN1B) is a rare MEN1 phenocopy. These syndromes are on the NCI list because their management is oncological: surveillance, prophylactic surgery and, when tumours spread, targeted therapy.\n\nManagement is genotype-driven. In MEN2, the American Thyroid Association (2015) assigns RET codons to risk levels that set the age of prophylactic thyroidectomy (within the first year for M918T, before age 5 for codon 634, later with calcitonin monitoring for moderate-risk codons), an intervention that prevents MTC in carriers identified early. Pheochromocytoma must be excluded before any surgery. Advanced RET-mutant MTC is treated with selpercatinib, which outperformed cabozantinib or vandetanib in the randomised LIBRETTO-531 trial (NEJM 2023), with pralsetinib as an alternative. In MEN1, surveillance (calcium and PTH, gastrin and fasting gut hormones, pituitary hormones, pancreatic MRI or endoscopic ultrasound) begins in childhood; parathyroidectomy, proton pump inhibitors for gastrinoma, and surgery for PanNETs above about 2 cm or functioning; advanced PanNETs are treated as sporadic NETs with somatostatin analogues, everolimus, sunitinib and 177Lu-DOTATATE.\n\nOpen problems are the timing of pancreatic surgery in MEN1, the lack of menin-directed therapy for MEN1 tumours (menin inhibitors developed for leukaemia work by a different mechanism), and equitable access to genetic testing and lifelong surveillance.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia","links":[{"label":"NCI PDQ: multiple endocrine neoplasia syndromes","url":"https://www.cancer.gov/types/multiple-endocrine-neoplasia"},{"label":"ATA medullary thyroid carcinoma guideline (2015)","url":"https://doi.org/10.1089/thy.2014.0335"},{"label":"MEN1 clinical practice guidelines (JCEM 2012)","url":"https://doi.org/10.1210/jc.2012-1230"},{"label":"LIBRETTO-531 (NEJM 2023)","url":"https://doi.org/10.1056/NEJMoa2309719"}],"tags":["nci-coverage","rare","endocrine","hereditary"],"related":["neuroendocrine","thyroid","pheochromocytoma-paraganglioma","lu-177"],"indications":[],"sections":[],"technologies":["prrt","sstr-pet"],"targets":["sstr2"],"drugs":["cabozantinib","everolimus","sunitinib","lutathera"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"MEN1 affects about 2 to 3 per 100,000 people and MEN2 about 1 in 30,000; both are inherited in an autosomal dominant pattern with near-complete penetrance.","subtypes":["MEN1 (menin; parathyroid, pancreatic NET, pituitary)","MEN2A (RET; medullary thyroid carcinoma, pheochromocytoma, parathyroid)","MEN2B (RET M918T; early MTC, pheochromocytoma, mucosal neuromas)","Familial medullary thyroid carcinoma (MEN2A variant)","MEN4 (CDKN1B)"],"biomarkers":["Germline MEN1, RET or CDKN1B mutation (diagnostic; codon defines MEN2 risk level)","Calcitonin and CEA (MTC surveillance)","Calcium and PTH, gastrin, fasting glucose and insulin, prolactin and IGF-1 (MEN1 surveillance)","Plasma metanephrines before any surgery (pheochromocytoma exclusion)","Pancreatic imaging (MRI, endoscopic ultrasound, 68Ga-DOTATATE PET)"],"standardOfCare":[{"setting":"MEN2 carriers (RET-positive)","approach":"Prophylactic total thyroidectomy timed by ATA risk level (highest risk within the first year, high risk before age 5, moderate risk guided by calcitonin); annual screening for pheochromocytoma and hyperparathyroidism.","refs":["thyroid","pheochromocytoma-paraganglioma"],"guideline":{"version":"American Thyroid Association medullary thyroid carcinoma guideline 2015","url":"https://doi.org/10.1089/thy.2014.0335"}},{"setting":"Advanced RET-mutant medullary thyroid carcinoma","approach":"Selpercatinib (LIBRETTO-531: superior to cabozantinib or vandetanib); pralsetinib, cabozantinib or vandetanib as alternatives.","refs":["cabozantinib"],"guideline":{"nccn":"Category 1 (selpercatinib)","version":"NCCN Thyroid Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470"}},{"setting":"MEN1 carriers","approach":"Surveillance from childhood; subtotal or total parathyroidectomy with autotransplantation for hyperparathyroidism; proton pump inhibitors for gastrinoma; resection of functioning or larger PanNETs; sporadic NET pathways (somatostatin analogues, everolimus, sunitinib, PRRT) for advanced disease.","refs":["everolimus","sunitinib","lutathera","prrt","neuroendocrine"],"guideline":{"version":"MEN1 clinical practice guidelines (Thakker, JCEM 2012)","url":"https://doi.org/10.1210/jc.2012-1230"}}],"stateOfArt":["MEN2 is the clearest example of genotype-directed prevention in oncology: a RET codon result sets the age of an operation that prevents a lethal cancer.","Selpercatinib converted RET-mutant MTC from multikinase-inhibitor territory into precision oncology, with better responses and fewer toxicities in a randomised comparison.","MEN1 surveillance protocols detect pancreatic NETs early, and 68Ga-DOTATATE PET and endoscopic ultrasound have replaced CT for pancreatic screening in many centres.","Cascade genetic testing of relatives, often in childhood, is standard and effective."],"history":[{"year":1954,"title":"Wermer describes familial adenomatosis of endocrine glands (MEN1)","refs":[]},{"year":1961,"title":"Sipple describes the association of pheochromocytoma and thyroid carcinoma (MEN2)","refs":[]},{"year":1993,"title":"RET mutations cause MEN2A","note":"Mulligan and colleagues, Nature; Donis-Keller and colleagues.","refs":[]},{"year":1997,"title":"MEN1 gene cloned","note":"Chandrasekharappa and colleagues, Science; menin identified.","refs":[]},{"year":2015,"title":"ATA guideline: codon-based timing of prophylactic thyroidectomy","refs":["thyroid"]},{"year":2020,"title":"Selpercatinib and pralsetinib approved for RET-mutant MTC","refs":[]},{"year":2023,"title":"LIBRETTO-531: selpercatinib beats multikinase inhibitors in RET-mutant MTC","note":"Hadoux and colleagues, NEJM.","refs":[]}],"pipeline":["lutathera","everolimus"],"openProblems":["MEN1 has no menin-restoring or pathway-directed therapy; PanNET progression remains the main cause of death, addressed by earlier detection and NET therapies.","Timing and extent of pancreatic surgery in MEN1: prospective registries are comparing strategies.","Resistance to selpercatinib (RET solvent-front mutations): next-generation RET inhibitors are in trials.","Lifelong surveillance costs and psychological burden in carriers identified as children."],"route":"/indications/multiple-endocrine-neoplasia/"}
{"id":"neuroblastoma","kind":"indication","name":"Neuroblastoma (paediatric)","aka":[],"tldr":"Neuroblastoma is a childhood nerve-cell cancer where anti-GD2 antibodies and, recently, GD2 CAR-T have improved survival in high-risk disease.","summary":"Neuroblastoma arises from developing sympathetic nerve cells, usually in the adrenal gland or along the spine, and is the most common cancer of infants and the most common extracranial solid tumour of childhood. It spans the widest clinical range in oncology: some infant tumours (stage MS) regress without treatment, while high-risk disease (about half of patients, defined by INRG stage, age over 18 months, MYCN amplification and other genomic features) is cured in only 50-60% despite the most intensive therapy given to children, which is where anti-GD2 antibodies and CAR-T have made their gains. ALK mutations (~10%) are the main druggable driver; MYCN, though not directly druggable, points to polyamine and ALK biology.\n\nHigh-risk therapy is a year-long sequence: five to six cycles of induction chemotherapy, surgery, myeloablative chemotherapy with autologous stem-cell rescue (tandem transplant in North America after ANBL0532; busulfan-melphalan single transplant in Europe after HR-NBL1), radiotherapy to the primary site, then anti-GD2 immunotherapy (dinutuximab or dinutuximab beta with GM-CSF; IL-2 abandoned after HR-NBL1) and isotretinoin. Anti-GD2 antibody raised survival by about 20 points (ANBL0032). Since December 2023, two years of oral eflornithine (DFMO) is approved as maintenance on the strength of an externally controlled study; naxitamab and irinotecan-temozolomide-dinutuximab treat relapse; lorlatinib is being added for ALK-aberrant tumours and 131I-MIBG tested in induction (ANBL1531).\n\nNeuroblastoma is also where CAR-T first produced lasting cures in a solid tumour: GD2-CART01 (Bambino Gesù, NEJM 2023) achieved 63% responses and 33% complete remissions in relapsed disease, with some remissions lasting more than a decade. The open questions are whether cell therapy can consolidate first-line remission, how to reduce the lifelong burden of hearing loss, infertility and second cancers in survivors, how to treat MYCN-amplified relapse, and how to bring anti-GD2 therapy to the majority of children in the world who cannot access it.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroblastoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroblastoma"}],"tags":["paediatric","spike"],"related":["i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","mibg-theranostics"],"targets":[],"drugs":[],"companies":["y-mabs"],"institutions":["mskcc","dana-farber"],"pathways":[],"terms":[],"trials":["nct04724369"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"~7-8% of childhood cancers; ~800 US cases a year; median age at diagnosis ~18 months; 5-year survival >90% for low/intermediate risk and ~50-60% for high risk.","subtypes":["Very-low and low risk (L1, MS in infants; often observation or surgery alone)","Intermediate risk (L2, M in infants; moderate chemotherapy)","High risk (stage M >18 months, or MYCN-amplified at any age)","ALK-mutated or amplified (~10%; lorlatinib-responsive)","MYCN-amplified (~20%)","Relapsed/refractory (MIBG-avid vs non-avid; marrow vs soft-tissue)","Ganglioneuroblastoma / ganglioneuroma (differentiated spectrum)","Opsoclonus-myoclonus-associated (paraneoplastic)"],"biomarkers":["MYCN amplification","ALK mutation","Age, stage, ploidy","Segmental chromosome aberrations","INRG stage and image-defined risk factors","Age (<18 months)","MYCN amplification (FISH)","ALK mutation/amplification","11q aberration, 1p deletion, ploidy, segmental chromosomal aberrations","INPC histology","Urinary catecholamines (VMA/HVA)","123I-MIBG Curie score / 18F-MFBG PET","Bone marrow minimal residual disease (PHOX2B, TH qPCR)","GD2 expression (near-universal)"],"standardOfCare":[{"setting":"High-risk","approach":"Induction chemo → surgery → tandem transplant → RT → anti-GD2 + isotretinoin; lorlatinib if ALK-mutant.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (COG risk groups)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Very-low / low risk (L1, MS)","approach":"Observation with serial imaging for asymptomatic L1/MS (many regress); surgery alone for resectable L1; short chemotherapy only for symptoms or progression.","refs":[],"guideline":{"nccn":"COG/SIOPEN low-risk protocols (observation or surgery)","version":"COG ANBL1232 / SIOPEN LINES"}},{"setting":"Intermediate risk","approach":"2-8 cycles of moderate chemotherapy (carboplatin, etoposide, cyclophosphamide, doxorubicin) guided by response and biology; surgery; isotretinoin in some protocols.","refs":[]},{"setting":"High risk: induction","approach":"5-6 cycles (COG: topotecan-cyclophosphamide × 2 then cisplatin-etoposide, cyclophosphamide-doxorubicin-vincristine; SIOPEN: rapid COJEC); stem-cell harvest; ANBL1531 adds 131I-MIBG (randomised) or lorlatinib (ALK); ANBL17P1 adds dinutuximab to induction.","refs":["anbl1531","i131-mibg"],"guideline":{"nccn":"COG ANBL1531 backbone","version":"COG 2026"}},{"setting":"High risk: local control","approach":"Surgical resection of primary after induction (gross total where safe); external-beam radiotherapy 21.6 Gy to primary site (boost to residual) and MIBG-avid metastatic sites; proton therapy where available.","refs":[]},{"setting":"High risk: consolidation","approach":"Tandem autologous transplant (thiotepa-cyclophosphamide, then CEM) in North America (ANBL0532); single busulfan-melphalan transplant in Europe (HR-NBL1).","refs":[],"guideline":{"nccn":"COG standard (tandem); SIOPEN standard (BuMel)","version":"2026"}},{"setting":"High risk: post-consolidation","approach":"Anti-GD2 antibody (dinutuximab + GM-CSF + isotretinoin; dinutuximab beta in Europe, no IL-2) × 5-6 cycles; then eflornithine maintenance 2 years (US, 2023).","refs":[],"guideline":{"nccn":"Dinutuximab: FDA-approved standard; eflornithine: FDA-approved maintenance","version":"2026"}},{"setting":"Relapsed / refractory","approach":"Irinotecan-temozolomide + dinutuximab or naxitamab (ANBL1221); naxitamab + GM-CSF for marrow/bone disease; 131I-MIBG for MIBG-avid disease; lorlatinib for ALK; GD2 CAR-T (Italy, trials); DFMO-based maintenance; palliative radiotherapy.","refs":["i131-mibg"]},{"setting":"Survivorship","approach":"Audiology (platinum, DFMO), endocrine and fertility follow-up, cardiac surveillance (anthracycline), second-malignancy screening, neurocognitive support; lifelong late-effects clinic.","refs":[]}],"stateOfArt":["Anti-GD2 raised high-risk survival to ~60%.","GD2 CAR-T responses.","Anti-GD2 immunotherapy after transplant is standard worldwide (ANBL0032), with IL-2 removed after HR-NBL1 showed no benefit.","Tandem transplant (North America) and busulfan-melphalan (Europe) are the two evidence-based consolidation standards.","Eflornithine is the first oral maintenance therapy approved (December 2023), on an externally controlled study.","GD2 CAR-T produced durable complete remissions in relapsed neuroblastoma, the first such result in a childhood solid tumour.","ALK inhibition with lorlatinib for ALK-aberrant tumours and 131I-MIBG during induction are being tested in ANBL1531.","Risk-adapted de-escalation: many infants and low-risk patients are observed or cured with surgery alone."],"history":[{"year":1910,"title":"James Homer Wright describes neuroblastoma and its rosettes","refs":[]},{"year":1971,"title":"Spontaneous regression of stage IV-S (now MS) disease recognised (Evans staging)","refs":[]},{"year":1983,"title":"MYCN amplification linked to aggressive disease (Brodeur, Schwab)","refs":[]},{"year":1985,"title":"131I-MIBG therapy first used in relapsed neuroblastoma","refs":["mibg-theranostics"]},{"year":1999,"title":"CCG-3891: myeloablative therapy with autologous rescue and isotretinoin improve survival","refs":[]},{"year":2008,"title":"ALK mutations identified as a hereditary and somatic driver","refs":[]},{"year":2009,"title":"INRG classification unifies international risk grouping","refs":[]},{"year":2010,"title":"Anti-GD2 (ch14.18) improves EFS","refs":[]},{"year":2010,"title":"ANBL0032: anti-GD2 immunotherapy raises survival ~20 points (NEJM)","refs":[]},{"year":2015,"title":"Dinutuximab approved (US); dinutuximab beta in EU 2017","refs":[]},{"year":2017,"title":"HR-NBL1: busulfan-melphalan beats CEM; IL-2 adds no benefit (2018)","refs":[]},{"year":2019,"title":"ANBL0532: tandem transplant improves EFS (JAMA)","refs":[]},{"year":2020,"title":"Naxitamab approved for relapsed disease (accelerated)","refs":[]},{"year":2023,"title":"GD2 CAR-T phase 1/2 in NEJM","refs":[]},{"year":2023,"title":"GD2-CART01 in NEJM: durable CAR-T remissions in a solid tumour; eflornithine approved (13 Dec)","refs":[]},{"year":2025,"title":"Long-term GD2 CAR-T follow-up (Nature Medicine); naxitamab primary-refractory phase 2 (75% CR); eflornithine EU filing","refs":[]},{"year":2026,"title":"ANBL1531 MIBG randomisation maturing; ALK arm reports","refs":["anbl1531"]}],"pipeline":["anbl1531","i131-mibg","idea-mfbg-pet-replaces-mibg","mibg-theranostics","y-mabs"],"openProblems":["Relapsed high-risk disease.","Long-term toxicity of intensive therapy.","Relapsed high-risk neuroblastoma is rarely curable; MYCN-amplified relapse worst of all.","Anti-GD2 therapy causes severe neuropathic pain; less painful antibody formats (e.g., humanised, Fc-engineered) and CAR-T are needed.","Long-term toxicity of tandem transplant, cisplatin (hearing loss), and radiation in children who will live 70 years.","Eflornithine's approval rests on an external control; a randomised trial is unlikely, so uncertainty persists.","Access: anti-GD2 antibodies are expensive and unavailable in most low- and middle-income countries where most children with cancer live.","MYCN remains undruggable directly; polyamine and Aurora/BET strategies are indirect.","GD2 CAR-T needs randomised evidence and manufacturing at scale; only a few centres can deliver it.","Imaging burden: repeated MIBG scans with sedation; MFBG PET adoption is slow."],"route":"/indications/neuroblastoma/"}
{"id":"neuroblastoma-high-risk","kind":"indication","name":"High-risk neuroblastoma","aka":["INRG high-risk neuroblastoma","Metastatic neuroblastoma","MYCN-amplified neuroblastoma","Stage 4 neuroblastoma"],"tldr":"High-risk neuroblastoma has spread widely in a child over 18 months old or carries extra copies of the MYCN gene. Treatment lasts about 18 months and uses every tool: chemotherapy, surgery, high-dose chemotherapy with stem cell rescue, radiotherapy, and the anti-GD2 antibody dinutuximab, which raised survival in ANBL0032; eflornithine, given afterwards, was approved in 2023 to lower relapse.","summary":"High-risk disease is stage M neuroblastoma in a child over 18 months, MYCN-amplified disease at any age and stage, and a few L2 and infant M cases with unfavourable genetics. Treatment runs in blocks. Induction with five or six cycles (cyclophosphamide and topotecan, cisplatin and etoposide, cyclophosphamide with doxorubicin and vincristine in the COG regimen; rapid COJEC in Europe) brings most children to a partial response and clears the marrow; surgery removes the primary; consolidation with myeloablative chemotherapy and autologous stem cell rescue follows; radiotherapy to the primary site and residual metastases; then post-consolidation immunotherapy with an anti-GD2 antibody and isotretinoin for six months. CCG-3891, reported in 1999, established both myeloablative therapy with autologous marrow rescue and 13-cis-retinoic acid maintenance: three-year event-free survival 34 percent against 22 percent with transplant, and 46 percent against 29 percent with retinoic acid.\n\nANBL0032 randomised 226 children after transplant to isotretinoin alone or with the chimeric anti-GD2 antibody ch14.18 (dinutuximab), GM-CSF and interleukin-2: two-year event-free survival 66 percent against 46 percent and overall survival 86 percent against 75 percent, and dinutuximab was approved in March 2015. SIOPEN HR-NBL1 showed that busulfan and melphalan beat carboplatin, etoposide and melphalan as the myeloablative regimen, three-year event-free survival 50 percent against 38 percent, and that adding interleukin-2 to dinutuximab beta brought toxicity without benefit. COG ANBL0532 showed tandem transplant with thiotepa-cyclophosphamide then carboplatin-etoposide-melphalan beat a single transplant, three-year event-free survival 61.6 percent against 48.4 percent. Eflornithine (DFMO), an ornithine decarboxylase inhibitor that lowers MYCN-driven polyamine synthesis, was approved in December 2023 as two years of maintenance after immunotherapy on the basis of the NMTRC003 and 003B single-arm studies compared with matched ANBL0032 controls, the first approval in neuroblastoma on an external control. Naxitamab, a humanised anti-GD2 antibody given with GM-CSF, was granted accelerated approval in November 2020 for relapsed or refractory disease in bone or marrow.\n\nAbout half of children still relapse, and relapsed high-risk disease is rarely cured. Irinotecan and temozolomide with dinutuximab (ANBL1221) is the standard relapse chemo-immunotherapy; iodine-131 MIBG delivers targeted radiation to the roughly 90 percent of tumours that take up the tracer and is being tested in induction in ANBL1531, which also gives lorlatinib to the roughly one in ten children whose tumours carry an ALK mutation after the NANT phase 1 showed responses in relapsed ALK-mutant disease. GD2 CAR T-cells produced remissions in relapsed children in the Bambino Gesù phase 1/2 trial reported in 2023, anti-GD2 antibody is being moved into induction alongside chemotherapy, and fluorine-18 MFBG PET may replace MIBG scans. The survivors carry the heaviest late-effect burden in childhood oncology: cisplatin hearing loss in most, infertility, growth failure, cardiac and renal damage, and second cancers.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Neuroblastoma","links":[{"label":"Wikipedia: Neuroblastoma","url":"https://en.wikipedia.org/wiki/Neuroblastoma"},{"label":"NCI PDQ: Neuroblastoma Treatment","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}],"tags":["subtype-page","paediatric"],"related":["f-18","i-131"],"indications":[],"sections":[],"technologies":["mibg-theranostics"],"targets":[],"drugs":[],"companies":["y-mabs"],"institutions":[],"pathways":[],"terms":["curie-siopen-score"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"About half of children with neuroblastoma have high-risk disease, metastatic at over 18 months of age or MYCN-amplified at any age; it accounts for around one in eight childhood cancer deaths, and only about half of children are cured despite the most intensive treatment given to any child.","subtypes":["Stage M neuroblastoma over 18 months without MYCN amplification","MYCN-amplified neuroblastoma at any age or stage (about a fifth of all neuroblastoma)","ALK-mutated or ALK-amplified high-risk neuroblastoma (lorlatinib added in ANBL1531)","Ultra-high-risk neuroblastoma (poor end-of-induction response, or MYCN amplification with ALK or TERT alterations)","Relapsed or refractory high-risk neuroblastoma (MIBG-avid and MIBG-non-avid; bone and marrow versus soft tissue)","Adolescent and adult neuroblastoma (indolent, chemotherapy-resistant; ALK and ATRX alterations)"],"biomarkers":["MYCN amplification","ALK mutation or amplification","11q loss, 1p loss and 17q gain","TERT rearrangement and ATRX loss (telomere maintenance)","MIBG avidity and Curie or SIOPEN score","End-of-induction response (INRC)","Marrow minimal residual disease by GD2 synthase or PHOX2B PCR","Urinary catecholamine metabolites"],"standardOfCare":[{"setting":"Induction","approach":"Five or six cycles of cyclophosphamide-topotecan, cisplatin-etoposide and cyclophosphamide-doxorubicin-vincristine (COG) or rapid COJEC (SIOPEN); iodine-131 MIBG and, for ALK-mutant disease, lorlatinib within ANBL1531; surgery after induction.","refs":["anbl1531","i131-mibg","mibg-theranostics"],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Consolidation","approach":"Busulfan-melphalan (HR-NBL1) or tandem thiotepa-cyclophosphamide then carboplatin-etoposide-melphalan (ANBL0532) with autologous stem cell rescue.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Local control","approach":"Radiotherapy to the primary site bed and residual MIBG-avid metastases after transplant.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Post-consolidation","approach":"Dinutuximab with GM-CSF and isotretinoin for five cycles (ANBL0032; interleukin-2 dropped after HR-NBL1), then two years of eflornithine maintenance.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Relapsed or refractory","approach":"Irinotecan-temozolomide with dinutuximab (ANBL1221) or naxitamab with GM-CSF; iodine-131 MIBG for avid disease; lorlatinib for ALK-mutant disease; GD2 CAR T-cells in trials.","refs":["temozolomide","i131-mibg"],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}},{"setting":"Survivorship","approach":"Hearing, cardiac, renal, endocrine, fertility and second-cancer follow-up for life.","refs":[],"guideline":{"version":"NCI PDQ: Neuroblastoma Treatment (health professional version)","url":"https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq"}}],"stateOfArt":["Anti-GD2 immunotherapy after transplant raised two-year event-free survival from 46 to 66 percent in ANBL0032 and is standard worldwide.","Tandem transplant (ANBL0532) and busulfan-melphalan (HR-NBL1) each beat the older single-transplant regimens.","Eflornithine maintenance, approved in 2023 on an external-control comparison, and lorlatinib for ALK-mutant disease are the newest additions; GD2 CAR T-cells have produced remissions in relapse."],"history":[{"year":1985,"title":"Iodine-131 MIBG therapy first given for neuroblastoma","refs":["i131-mibg","mibg-theranostics"]},{"year":1999,"title":"CCG-3891: myeloablative therapy with autologous rescue and 13-cis-retinoic acid each improve event-free survival","refs":[]},{"year":2010,"title":"ANBL0032: anti-GD2 antibody with GM-CSF and interleukin-2 raises two-year event-free survival from 46 to 66 percent","refs":[]},{"year":2015,"title":"Dinutuximab approved for high-risk neuroblastoma","refs":[]},{"year":2017,"title":"HR-NBL1: busulfan-melphalan beats carboplatin-etoposide-melphalan","refs":[]},{"year":2019,"title":"ANBL0532: tandem transplant beats single transplant","refs":[]},{"year":2020,"title":"Naxitamab granted accelerated approval for relapsed or refractory bone or marrow disease","refs":[]},{"year":2023,"title":"Eflornithine approved as maintenance on an external-control comparison; GD2 CAR T-cells produce remissions in relapsed disease","refs":[]}],"pipeline":["anbl1531","i131-mibg","idea-mfbg-pet-replaces-mibg","mibg-theranostics"],"openProblems":["About half of children relapse and relapsed disease is rarely cured.","MYCN has no direct inhibitor; eflornithine and lorlatinib act around it.","Cisplatin hearing loss, infertility and second cancers in survivors of the most intensive regimen in paediatric oncology."],"parent":"neuroblastoma","route":"/indications/neuroblastoma-high-risk/"}
{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","aka":["Gastrointestinal Neuroendocrine Tumors","Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)"],"tldr":"A family of usually slow-growing tumours that start in hormone-producing cells of the gut, pancreas and lungs. They pioneered the idea of using the same molecule to see a tumour on a scan and then to treat it with radiation.","summary":"Neuroendocrine neoplasms range from indolent grade 1 tumours that patients live with for decades to poorly differentiated neuroendocrine carcinomas that behave like small-cell lung cancer. Most arise in the small bowel, pancreas, rectum or lung; many secrete hormones (serotonin, insulin, gastrin) that cause syndromes, and most well-differentiated tumours express somatostatin receptor 2 (SSTR2), which is the hinge of both diagnosis and therapy. Incidence has risen six-fold over 40 years, largely from incidental detection on imaging and endoscopy.\n\nTherapy is sequenced by grade, receptor status and tempo. Somatostatin analogues (octreotide, lanreotide) control symptoms and slow growth (PROMID, CLARINET). For progression, peptide receptor radionuclide therapy with 177Lu-DOTATATE (NETTER-1; NETTER-2 first line for grade 2-3) is standard, and 177Lu-edotreotide beat everolimus head-to-head in COMPETE (PFS 23.9 vs 14.1 months) with an FDA decision due August 2026. Targeted pills (everolimus, sunitinib, and since March 2025 cabozantinib after CABINET) and chemotherapy (CAPTEM for pancreatic NETs; platinum-etoposide for neuroendocrine carcinoma) fill in. Surgery and liver-directed therapy (resection, embolisation, ablation, transplant in rare cases) remain central because disease is often liver-dominant.\n\nThe frontier is alpha-emitting PRRT: 212Pb-DOTAMTATE (AlphaMedix) met all primary endpoints in phase 2 with a 54% response rate in PRRT-naive patients and Breakthrough designation, and 225Ac-DOTATATE (RYZ101) is in the phase 3 ACTION-1 trial after lutetium failure. SSTR antagonist ligands, dosimetry-personalised dosing, and combinations with CAPTEM or immunotherapy are being tested. Open problems include the lack of randomised evidence for sequencing, the absence of effective therapy for SSTR-negative and high-grade disease, a 2-3% risk of therapy-related leukaemia after PRRT, and isotope supply.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":["endocrine","spike"],"related":["sstr-pet-to-prrt","prrt-then-alpha-net","radiopharma-roadmap","beta-then-alpha","lu-177","ac-225","pb-212"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","pet","sstr-pet","prrt","pet-ct","radioembolisation-tare"],"targets":["sstr2","dll3"],"drugs":["iobenguane-i-131"],"companies":["sinotau-pharmaceutical","novartis","itm","orano-med","radiomedix","rayzebio","bms","pfizer"],"institutions":["mskcc","heidelberg-nct","royal-marsden"],"pathways":[],"terms":["net-grade-ki67","theranostics","alpha-vs-beta","dosimetry"],"trials":["netter-1","nct05459844","nct06398444","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"About 7 per 100,000 people per year in the US, rising six-fold since the 1970s; prevalence is high because many patients live for years (>170,000 living with NETs in the US).","subtypes":["Small-bowel (midgut) NET, often with carcinoid syndrome","Pancreatic NET (functioning: insulinoma, gastrinoma, glucagonoma; non-functioning)","Lung NET (typical and atypical carcinoid)","Rectal and appendiceal NET (often incidental, excellent prognosis)","Grade 3 well-differentiated NET","Neuroendocrine carcinoma (small- and large-cell), treated like SCLC","Hereditary: MEN1, VHL, NF1, TSC; paraganglioma/phaeochromocytoma (SDHx)"],"biomarkers":["Ki-67 grade","SSTR PET uptake","Chromogranin A","MEN1, DAXX/ATRX","Ki-67 index and mitotic count (WHO grade)","SSTR2 expression by 68Ga/64Cu-DOTATATE PET","FDG PET avidity (high-grade or dedifferentiated disease)","Chromogranin A (monitoring)","24-hour urinary 5-HIAA (carcinoid syndrome)","Germline MEN1, VHL, SDHx testing","MGMT status (CAPTEM response, investigational)"],"standardOfCare":[{"setting":"Localised","approach":"Resection.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced","approach":"SSA → 177Lu-DOTATATE → everolimus/cabozantinib/chemotherapy; alpha therapy in trials.","refs":["lutathera","ryz101"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Diagnosis and staging","approach":"Histology with Ki-67 grading; 68Ga/64Cu-DOTATATE PET/CT ± FDG PET; triple-phase CT or MRI of the liver; chromogranin A and syndrome-specific hormones; germline testing for pancreatic NETs and paragangliomas.","refs":["sstr-pet","net-grade-ki67"],"guideline":{"nccn":"Neuroendocrine and Adrenal Tumors","version":"NCCN 2026 / ENETS 2023"}},{"setting":"Localised disease","approach":"Surgical resection (including primary tumour resection with liver metastases where feasible); endoscopic resection for small rectal/gastric NETs; surveillance for small incidental lesions.","refs":[],"guideline":{"nccn":"Category 2A"}},{"setting":"Advanced, grade 1-2, SSTR-positive, first line","approach":"Somatostatin analogue (octreotide LAR or lanreotide); 177Lu-DOTATATE first line for grade 2-3 (NETTER-2) with high burden.","refs":["lutathera","prrt"],"guideline":{"nccn":"Category 1 (SSA); category 1 PRRT for grade 2-3 first line"}},{"setting":"Advanced, progression on SSA","approach":"PRRT with 177Lu-DOTATATE (or 177Lu-edotreotide if approved); everolimus; sunitinib (pancreatic); cabozantinib (CABINET, all sites).","refs":["lutathera","itm-11","compete","everolimus","radiant-3-4","sunitinib","cabozantinib","cabinet"],"guideline":{"nccn":"Category 1 for PRRT and cabozantinib; 2A sequencing"}},{"setting":"Advanced pancreatic NET needing tumour shrinkage","approach":"CAPTEM (E2211); PRRT; liver-directed therapy for hepatic-dominant disease.","refs":["radioembolisation-tare"],"guideline":{"nccn":"Category 2A"}},{"setting":"Carcinoid syndrome","approach":"SSA dose escalation; telotristat ethyl for refractory diarrhoea; octreotide infusion peri-procedurally; echocardiographic screening for carcinoid heart disease.","refs":[],"guideline":{"nccn":"Category 2A"}},{"setting":"Neuroendocrine carcinoma (poorly differentiated)","approach":"Platinum-etoposide (as in SCLC) ± PD-L1 inhibitor by extrapolation; FOLFIRINOX or CAPTEM in later lines; DLL3-directed agents in trials.","refs":[],"guideline":{"nccn":"Category 2A"}},{"setting":"After PRRT failure","approach":"Everolimus or cabozantinib; alpha PRRT in trials (ACTION-1, AlphaMedix); PRRT retreatment in selected patients.","refs":["ryz101","action-1","alphamedix","prrt-then-alpha-net"],"guideline":{"nccn":"Trials preferred"}},{"setting":"VHL-associated pancreatic NET","approach":"Belzutifan (approved 2021) for non-metastatic tumours not requiring immediate surgery.","refs":[],"guideline":{"nccn":"Category 2A"}}],"stateOfArt":["Theranostic paradigm; first-line PRRT in higher-grade disease.","Theranostic paradigm is routine: SSTR PET selects, 177Lu-DOTATATE treats, including first line for grade 2-3 disease.","First head-to-head radioligand-versus-drug trial (COMPETE) won on PFS; FDA decision on 177Lu-edotreotide due 28 August 2026.","Cabozantinib approved (2025) across pancreatic and extra-pancreatic NETs after prior therapy, with an 81% reduction in progression risk in lung/thymic NETs.","Alpha PRRT (212Pb-DOTAMTATE) met all phase 2 endpoints with Breakthrough designation; 225Ac-DOTATATE in phase 3.","Germline testing and syndrome-directed care (belzutifan for VHL) are standard for pancreatic NETs."],"history":[{"year":1907,"title":"Oberndorfer coins 'Karzinoid' for small-bowel tumours","refs":[]},{"year":1954,"title":"Carcinoid syndrome described (Thorson)","refs":[]},{"year":1987,"title":"Octreotide approved","refs":[]},{"year":1988,"title":"Octreotide approved for carcinoid syndrome","refs":[]},{"year":1994,"title":"111In-octreotide scintigraphy (OctreoScan) approved","note":"First SSTR imaging; later replaced by PET.","refs":["sstr-pet"]},{"year":2000,"title":"First 90Y- and 177Lu-DOTATOC/DOTATATE PRRT series (Rotterdam, Basel)","refs":["prrt"]},{"year":2009,"title":"PROMID: octreotide slows tumour growth","refs":[]},{"year":2011,"title":"Everolimus (RADIANT-3) and sunitinib approved for pancreatic NETs","refs":["radiant-3-4","everolimus","sunitinib"]},{"year":2014,"title":"CLARINET: lanreotide antiproliferative approval","refs":[]},{"year":2016,"title":"68Ga-DOTATATE PET (Netspot) approved; RADIANT-4 extends everolimus to lung/GI NETs","refs":["sstr-pet","radiant-3-4"]},{"year":2018,"title":"Lutathera approved","refs":["lutathera"]},{"year":2018,"title":"Lutathera approved (NETTER-1): PRRT enters standard care","refs":["lutathera","prrt"]},{"year":2020,"title":"SANET trials positive in China (surufatinib)","refs":[]},{"year":2024,"title":"NETTER-2: first-line PRRT","refs":[]},{"year":2024,"title":"NETTER-2: PRRT first line in grade 2-3; CABINET published; AlphaMedix Breakthrough designation","refs":["lutathera","cabinet","alphamedix"]},{"year":2025,"title":"Cabozantinib approved (March); COMPETE positive (ENETS, Lancet); AlphaMedix phase 2 meets all endpoints (October)","refs":["cabozantinib","compete","alphamedix-02"]},{"year":2026,"title":"FDA accepts 177Lu-edotreotide NDA (PDUFA 28 August); ACTION-1 dosimetry published; pancreatic subgroup of COMPETE at ENETS","refs":["itm-11","action-1"]}],"pipeline":["ryz101","itm-11","compete","alphamedix","alphamedix-02","action-1","prrt","sstr-pet","cabozantinib","idea-net-dosimetry-prrt","idea-net-antagonist-ligands","prrt-then-alpha-net","dll3"],"openProblems":["Neuroendocrine carcinoma (high grade) behaves like SCLC.","Sequencing of PRRT vs targeted therapy.","Sequencing is unproven: no randomised trial orders SSA, PRRT, everolimus, cabozantinib and chemotherapy.","SSTR-negative, FDG-avid and high-grade disease has few options; neuroendocrine carcinoma outcomes remain poor.","Therapy-related MDS/AML (~2-3%) and renal toxicity after PRRT; long-term data on retreatment are thin.","Overall survival benefits are hard to demonstrate because patients live for years and cross over.","Isotope supply (177Lu, 212Pb, 225Ac) and nuclear-medicine capacity limit access outside major centres.","Chromogranin A is an unreliable marker; better blood tests (NETest, ctDNA) are not validated for decisions.","Rare syndromic and paediatric NETs lack trials; hereditary carriers need lifelong surveillance protocols."],"route":"/indications/neuroendocrine/"}
{"id":"osteosarcoma","kind":"indication","name":"Osteosarcoma","aka":[],"tldr":"Osteosarcoma is the most common bone cancer, mostly in teenagers. Chemotherapy plus surgery cures about two-thirds when it has not spread; because no new drug has beaten that chemotherapy in a large trial in 30 years, the next gains are being sought in cellular therapy against GD2, HER2 and B7-H3.","summary":"Osteosarcoma is a high-grade bone sarcoma with chaotic genomes (TP53 and RB1 loss, chromothripsis, no recurrent targetable driver), arising in the metaphyses of long bones during growth spurts and in older adults after Paget disease or radiation. Germline predisposition (Li-Fraumeni, hereditary retinoblastoma, Rothmund-Thomson) accounts for a meaningful fraction.\n\nStandard therapy since the 1980s is neoadjuvant MAP (high-dose methotrexate, doxorubicin, cisplatin), limb-salvage surgery, and adjuvant MAP; histologic response (≥90% necrosis) is prognostic but intensifying therapy for poor responders (EURAMOS-1: adding ifosfamide-etoposide) did not help, nor did interferon maintenance. Mifamurtide (liposomal MTP-PE) is approved in the EU (INT-0133) but not in the US. Lung metastases are resected whenever possible. Relapsed disease has ~20% survival; multikinase inhibitors (regorafenib in SARC024/REGOBONE, cabozantinib in CABONE, sorafenib) give short PFS gains. Novel approaches: GD2- and HER2-directed CAR-T, B7-H3 ADCs, radiopharmaceuticals (Ra-223, Sm-153), and biology from canine osteosarcoma.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Osteosarcoma","links":[{"label":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"},{"label":"EURAMOS-1 (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30214-5"},{"label":"NCI PDQ: osteosarcoma","url":"https://www.cancer.gov/types/bone/patient/osteosarcoma-treatment-pdq"}],"tags":["gap-fill","paediatric","sarcoma","aya"],"related":["ra-223","sm-153"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":["her2","b7h3"],"drugs":["cabozantinib","docetaxel","radium-223"],"companies":["bayer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"The most common primary bone cancer; ~1,000 cases per year in the US with peaks in adolescence and over 60 (Paget disease, radiation); 5-year survival ~70% localised, ~25% metastatic.","subtypes":["Conventional high-grade (osteoblastic, chondroblastic, fibroblastic)","Telangiectatic","Small cell","Low-grade central and parosteal (surgery alone)","Periosteal (intermediate grade)","Secondary (Paget, post-radiation)"],"biomarkers":["Histologic necrosis after neoadjuvant chemotherapy (≥90% good response)","Alkaline phosphatase and LDH","Metastases at diagnosis (lung, bone)","Germline TP53 / RB1 / RECQL4","GD2, HER2, B7-H3 expression (trial eligibility)","ctDNA copy-number burden (prognostic, emerging)"],"standardOfCare":[{"setting":"Localised high-grade","approach":"Neoadjuvant MAP (methotrexate, doxorubicin, cisplatin) ×2 cycles, limb-salvage resection with wide margins (amputation if required), adjuvant MAP to ~29 weeks; mifamurtide added in EU.","refs":[],"guideline":{"nccn":"Category 1 (MAP)","version":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"}},{"setting":"Metastatic at diagnosis","approach":"Same chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%.","refs":[],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}},{"setting":"Relapsed","approach":"Surgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs).","refs":["cabozantinib","docetaxel"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}},{"setting":"Unresectable / axial","approach":"Carbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational).","refs":["radium-223"]}],"stateOfArt":["MAP chemotherapy, unchanged since the 1980s, remains the standard; EURAMOS-1 (2,260 patients) closed the door on intensification.","Limb salvage is possible in >90% with expandable prostheses for growing children.","Multikinase inhibitors are the only agents with randomised evidence at relapse, and the gain is months.","Immunotherapy has largely failed (checkpoint inhibitors inactive); cellular therapy against GD2/HER2/B7-H3 is the active frontier."],"history":[{"year":1970,"title":"Amputation alone cures <20%; lung metastases the rule","refs":[]},{"year":1972,"title":"High-dose methotrexate with leucovorin rescue (Jaffe) and adriamycin (Cortes) show activity","refs":[]},{"year":1979,"title":"Rosen's T-10: neoadjuvant chemotherapy and limb salvage","refs":[]},{"year":1986,"title":"Randomised proof that adjuvant chemotherapy cures (Link, NEJM; MIOS)","refs":[]},{"year":2008,"title":"INT-0133: mifamurtide improves overall survival; EU approval 2009","refs":[]},{"year":2016,"title":"EURAMOS-1: no benefit from intensifying for poor responders or interferon for good responders","refs":[]},{"year":2019,"title":"Regorafenib (SARC024, REGOBONE) and cabozantinib (CABONE) show activity at relapse","refs":["cabozantinib"]}],"pipeline":["cabozantinib","radium-223","b7h3"],"openProblems":["No survival improvement since the 1980s; metastatic and relapsed disease ~20-30% survival.","No recurrent druggable driver; genomic chaos.","Chemotherapy toxicity: cardiotoxicity, hearing loss, infertility, second cancers.","Rarity fragments trials; international cooperation (EURAMOS) needed for every question."],"route":"/indications/osteosarcoma/"}
{"id":"pancreatic-net","kind":"indication","name":"Pancreatic neuroendocrine tumours","aka":["pNET","Islet cell tumour","Pancreatic NET","Insulinoma","Gastrinoma","Non-functioning pancreatic neuroendocrine tumour"],"tldr":"Pancreatic neuroendocrine tumours arise from the hormone-producing islet cells of the pancreas and behave very differently from ordinary pancreatic cancer, often growing for years. Surgery cures localised tumours; advanced disease is treated in sequence with somatostatin analogues, lutetium-177 dotatate, targeted tablets and oral chemotherapy, and a minority secrete insulin or gastrin.","summary":"Pancreatic neuroendocrine tumours arise from islet cells and are graded by Ki-67 like other neuroendocrine tumours, but their genetics are their own: MEN1 is the most commonly mutated gene in sporadic tumours, with DAXX or ATRX loss and mutations in the mTOR pathway following, while KRAS and TP53, the drivers of ductal adenocarcinoma, are absent. Most are non-functioning and present as a mass or as liver metastases; the functioning minority cause syndromes, insulinoma with fasting hypoglycaemia (usually benign and cured by enucleation), gastrinoma with the ulcer disease of Zollinger-Ellison syndrome (controlled with proton-pump inhibitors, often malignant and often part of MEN1), and rarer glucagonomas and VIPomas. Germline testing is offered because MEN1, VHL, neurofibromatosis type 1 and tuberous sclerosis all predispose, and small non-functioning tumours under about two centimetres are often watched rather than removed.\n\nSurgery is curative for localised disease: enucleation or distal pancreatectomy for small tumours and a Whipple procedure for those in the head. For advanced disease, 2011 brought two tablets at once. RADIANT-3 (New England Journal of Medicine 2011) randomised 410 patients with progressive tumours to everolimus or placebo and lengthened progression-free survival from 4.6 to 11.0 months; the sunitinib phase 3 (New England Journal of Medicine 2011) was stopped early after 171 patients with 11.4 against 5.5 months. CLARINET (2014), in which almost half the patients had pancreatic tumours, established lanreotide as antiproliferative first-line therapy, and the E2211 trial (Journal of Clinical Oncology 2023) showed that adding capecitabine to temozolomide lengthened progression-free survival from 14.4 to 22.7 months with a higher response rate, making CAPTEM the chemotherapy of choice when shrinkage is needed. Streptozocin, approved in 1982, remains a guideline option.\n\nRadioligand therapy and cabozantinib have since reordered the sequence. Lutathera's 2018 approval covered all gastroenteropancreatic tumours on the strength of NETTER-1 in midgut disease, and NETTER-2 (Lancet 2024), in which more than half the patients had pancreatic tumours, showed first-line lutetium-177 dotatate lengthened progression-free survival from 8.5 to 22.8 months in grade 2 and 3 disease. CABINET (New England Journal of Medicine 2024) randomised a separate pancreatic cohort to cabozantinib or placebo after prior therapy and lengthened progression-free survival from 4.4 to 13.8 months, leading to approval in March 2025. Belzutifan was approved in 2021 for VHL-associated pancreatic tumours not needing immediate surgery, and its LITESPARK-015 trial has a sporadic pancreatic NET cohort. COMPETE (Lancet 2025) and COMPOSE test 177Lu-edotreotide against everolimus and against chemotherapy, and hepatic-dominant disease is still treated with embolisation, ablation and resection.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Pancreatic_neuroendocrine_tumor","links":[{"label":"RADIANT-3 (NEJM 2011)","url":"https://doi.org/10.1056/NEJMoa1009290"},{"label":"Sunitinib in pancreatic NET (NEJM 2011)","url":"https://doi.org/10.1056/NEJMoa1003825"},{"label":"CABINET (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2403991"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pancreatic_neuroendocrine_tumor"}],"tags":["subtype-page","endocrine"],"related":["grade-3-net","lung-net","small-intestinal-net","lu-177"],"indications":[],"sections":[],"technologies":["sstr-pet","prrt","radioligand-therapy","radioembolisation-tare"],"targets":["sstr2"],"drugs":["lutathera","everolimus","sunitinib","cabozantinib","ga68-dotatate","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["net-grade-ki67","prrt-term"],"trials":["radiant-3-4","cabinet","nct03972488","netter-1","compete","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-2-lancet-2024","paper-cabinet-cabozantinib-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"A small minority of pancreatic cancers but the site with the most approved drugs of any neuroendocrine tumour; most are non-functioning and found on imaging, while insulinomas and gastrinomas announce themselves through their hormones.","subtypes":["Non-functioning pancreatic NET (the majority, found as a mass or liver metastases)","Insulinoma (fasting hypoglycaemia, usually benign, cured by enucleation)","Gastrinoma and Zollinger-Ellison syndrome (often duodenal or pancreatic head, often MEN1)","Glucagonoma, VIPoma and somatostatinoma (rare functioning tumours)","MEN1- and VHL-associated pancreatic NET (multiple, young onset)","Grade 1 to 2 pancreatic NET (somatostatin analogue, radioligand, everolimus, sunitinib, cabozantinib)","Grade 3 well-differentiated pancreatic NET (see the grade 3 record)"],"biomarkers":["Ki-67 index and mitotic count (WHO grade)","Chromogranin A (monitoring)","Somatostatin receptor PET (staging and radioligand eligibility)","Fasting glucose, insulin, C-peptide and proinsulin (insulinoma)","Fasting gastrin and gastric pH (gastrinoma)","Germline MEN1, VHL, NF1 and TSC testing","MEN1, DAXX and ATRX status in the tumour (prognostic, research)","MGMT status (CAPTEM response, investigational)"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Contrast CT or MRI, somatostatin receptor PET, biopsy with Ki-67 grading, chromogranin A, hormone assays where a syndrome is suspected, and germline testing.","refs":["sstr-pet","ga68-dotatate","net-grade-ki67"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Localised, resectable","approach":"Enucleation or distal pancreatectomy for small tumours, Whipple procedure for tumours in the head, lymphadenectomy for tumours over two centimetres; surveillance for small non-functioning tumours.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Functioning syndromes","approach":"Surgery for insulinoma with diazoxide or everolimus to control hypoglycaemia beforehand; high-dose proton-pump inhibitors and resection for gastrinoma; somatostatin analogues for glucagonoma and VIPoma.","refs":["everolimus"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, first line","approach":"Lanreotide or octreotide (CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2); CAPTEM when shrinkage is needed.","refs":["lutathera","nct03972488","prrt"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Progression on a somatostatin analogue","approach":"Lutetium-177 dotatate; everolimus (RADIANT-3); sunitinib; cabozantinib (CABINET); CAPTEM or streptozocin-based chemotherapy.","refs":["lutathera","everolimus","radiant-3-4","sunitinib","cabozantinib","cabinet"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Liver-dominant disease","approach":"Resection, thermal ablation, chemoembolisation or radioembolisation, alongside systemic therapy.","refs":["radioembolisation-tare"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"VHL-associated pancreatic NET","approach":"Belzutifan for tumours not requiring immediate surgery (approved 2021).","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}}],"stateOfArt":["Five approved systemic drug classes (somatostatin analogues, radioligand therapy, mTOR inhibition, anti-angiogenic kinase inhibitors and oral chemotherapy) give years of sequential control.","NETTER-2 put lutetium-177 dotatate in first line for grade 2 to 3 disease and CABINET added cabozantinib after prior therapy.","Belzutifan was the first drug approved for a hereditary neuroendocrine syndrome, in VHL disease."],"history":[{"year":1927,"title":"Wilder describes hyperinsulinism from an islet cell tumour; first successful insulinoma resection follows in 1929","refs":[]},{"year":1955,"title":"Zollinger and Ellison describe the gastrinoma syndrome","refs":[]},{"year":1982,"title":"Streptozocin approved for metastatic islet cell carcinoma","refs":[]},{"year":2011,"title":"RADIANT-3 and the sunitinib phase 3 published; everolimus and sunitinib approved; MEN1, DAXX and ATRX mutations mapped by exome sequencing","refs":["radiant-3-4","everolimus","sunitinib"]},{"year":2014,"title":"CLARINET: lanreotide approved as antiproliferative therapy","refs":[]},{"year":2018,"title":"Lutathera approved for gastroenteropancreatic tumours","refs":["lutathera","prrt"]},{"year":2021,"title":"Belzutifan approved for VHL-associated pancreatic NET","refs":[]},{"year":2023,"title":"E2211 final analysis: CAPTEM beats temozolomide alone","refs":[]},{"year":2024,"title":"NETTER-2: first-line lutetium-177 dotatate in grade 2 to 3 disease; CABINET pancreatic cohort published","refs":["nct03972488","lutathera","cabinet"]},{"year":2025,"title":"Cabozantinib approved; COMPETE published","refs":["cabozantinib","compete"]}],"pipeline":["itm-11","compete","nct04919226","ryz101","action-1","alphamedix","nct05884255","idea-net-dosimetry-prrt"],"openProblems":["The best order of radioligand therapy, everolimus, sunitinib, cabozantinib and CAPTEM is unknown.","Which small non-functioning tumours can safely be watched rather than resected.","MGMT and other predictors of CAPTEM response are not validated for decisions.","Grade 3 well-differentiated tumours sit between the tumour and carcinoma paradigms and need their own trials."],"parent":"neuroendocrine","route":"/indications/pancreatic-net/"}
{"id":"pheochromocytoma-paraganglioma","kind":"indication","name":"Pheochromocytoma and paraganglioma (PPGL)","aka":["Pheochromocytoma","Paraganglioma","PPGL","Phaeochromocytoma"],"tldr":"Pheochromocytomas and paragangliomas are tumours of adrenaline-producing tissue that cause dangerous blood pressure surges. Surgery after careful blood-pressure blockade cures most, genetic testing finds an inherited cause in nearly half, and for the minority that spread there are now radioactive drugs that home to the tumour and, since 2025, the first oral targeted pill, belzutifan.","summary":"PPGL are catecholamine-secreting tumours of the adrenal medulla (pheochromocytoma) or extra-adrenal sympathetic and parasympathetic paraganglia. They have the highest heritability of any human tumour: about 40 percent carry germline mutations in one of more than 15 genes, grouped into cluster 1 (pseudohypoxia: SDHA/B/C/D, VHL, FH, EPAS1) and cluster 2 (kinase signalling: RET, NF1, TMEM127, MAX). SDHB carriers have the highest metastatic risk. Diagnosis rests on plasma free or urinary fractionated metanephrines, then anatomical imaging and functional imaging with 68Ga-DOTATATE PET (most sensitive for SDHx and metastatic disease) or 18F-FDOPA. Endocrine Society guidance recommends germline testing for every patient.\n\nSurgery after 7 to 14 days of alpha-adrenergic blockade is curative for localised disease, with cortical-sparing adrenalectomy in hereditary bilateral cases. Metastatic disease is treated to control catecholamine excess and tumour burden: 177Lu-DOTATATE for SSTR-positive tumours (NCCN-listed; prospective trials ongoing), high-specific-activity 131I-MIBG (iobenguane I-131, Azedra; FDA 2018, though the manufacturer later announced its commercial discontinuation), cyclophosphamide-vincristine-dacarbazine or temozolomide chemotherapy (particularly SDHB-mutant), and sunitinib, which improved progression-free survival versus placebo in the randomised FIRSTMAPPP trial (Lancet 2024). Belzutifan, the HIF-2alpha inhibitor first approved for VHL-associated tumours, received FDA approval on 14 May 2025 for locally advanced, unresectable or metastatic PPGL in patients aged 12 and older on the basis of the LITESPARK-015 cohort (objective response rate 26 percent), the first oral therapy approved for the disease and a direct hit on the pseudohypoxia biology of cluster 1 tumours.\n\nOpen problems are predicting metastasis (no histological criterion is reliable), lifelong surveillance of gene carriers, and sequencing radioligand, HIF-2alpha and kinase therapy.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Pheochromocytoma","links":[{"label":"NCI PDQ: pheochromocytoma and paraganglioma","url":"https://www.cancer.gov/types/pheochromocytoma"},{"label":"FDA approval of belzutifan for PPGL (May 2025)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pheochromocytoma-or-paraganglioma"},{"label":"Endocrine Society guideline 2014","url":"https://doi.org/10.1210/jc.2014-1498"},{"label":"FIRSTMAPPP (Lancet 2024)","url":"https://doi.org/10.1016/S0140-6736(23)02554-0"}],"tags":["nci-coverage","rare","endocrine"],"related":["f-18","ga-68","lu-177","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","prrt","mibg-theranostics","sstr-pet"],"targets":["sstr2"],"drugs":["lutathera","i131-mibg","sunitinib","temozolomide","cabozantinib"],"companies":["merck","novartis","pfizer"],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"About 2 to 8 cases per million people per year; roughly one in ten pheochromocytomas and a higher share of paragangliomas are metastatic, and about 40 percent of all cases are hereditary.","subtypes":["Adrenal pheochromocytoma","Sympathetic paraganglioma (abdominal, thoracic)","Head and neck (parasympathetic) paraganglioma, usually non-secreting","Hereditary PPGL (SDHx, VHL, RET/MEN2, NF1, MAX, TMEM127)","Metastatic PPGL"],"biomarkers":["Plasma free or urinary fractionated metanephrines","Germline panel testing (SDHA/B/C/D, SDHAF2, VHL, RET, NF1, MAX, TMEM127, FH, EPAS1)","SDHB immunohistochemistry (loss indicates SDHx)","68Ga-DOTATATE PET (SSTR2 expression; selects for PRRT)","123I-MIBG scintigraphy (selects for 131I-MIBG)","Tumour size, extra-adrenal location and SDHB status as metastatic risk factors"],"standardOfCare":[{"setting":"Localised, secreting","approach":"Alpha-blockade (phenoxybenzamine or doxazosin) for 7 to 14 days, volume expansion, then laparoscopic or open adrenalectomy; cortical-sparing surgery in hereditary bilateral disease.","refs":[],"guideline":{"version":"Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"All patients","approach":"Germline genetic testing and, for carriers, lifelong biochemical and imaging surveillance; cascade testing of relatives.","refs":[],"guideline":{"version":"Endocrine Society 2014","url":"https://doi.org/10.1210/jc.2014-1498"}},{"setting":"Metastatic or unresectable","approach":"Belzutifan (FDA May 2025, LITESPARK-015); 177Lu-DOTATATE for SSTR-positive disease; 131I-MIBG where available; sunitinib (FIRSTMAPPP); CVD or temozolomide chemotherapy for rapidly progressive or SDHB-mutant disease; alpha-blockade throughout.","refs":["lutathera","prrt","i131-mibg","mibg-theranostics","sunitinib","temozolomide"],"guideline":{"nccn":"Category 2A","version":"NCCN Neuroendocrine and Adrenal Tumors"}}],"stateOfArt":["Belzutifan is the first drug to target the pseudohypoxia biology (HIF-2alpha) shared by SDHx- and VHL-driven tumours, and the first oral therapy approved for PPGL (2025).","Theranostics matured here early: 123I-MIBG and 68Ga-DOTATATE imaging select patients for 131I-MIBG or 177Lu-DOTATATE treatment of the same target.","FIRSTMAPPP was the first randomised phase 2 in metastatic PPGL, showing that trials are possible in a disease this rare and that sunitinib delays progression.","Universal germline testing has turned PPGL into a model for hereditary cancer surveillance, with SDHB carriers identified before tumours form."],"history":[{"year":1886,"title":"Fränkel describes bilateral adrenal tumours in an 18-year-old","note":"Later shown by genetic analysis to be a case of MEN2.","refs":[]},{"year":1926,"title":"First successful resection (Roux in Lausanne, Mayo in Rochester)","refs":[]},{"year":2000,"title":"SDHD mutations in hereditary paraganglioma","note":"Baysal and colleagues, Science: metabolic enzyme genes as tumour suppressors.","refs":[]},{"year":2014,"title":"Endocrine Society guideline recommends germline testing for all","refs":[]},{"year":2018,"title":"High-specific-activity 131I-MIBG (Azedra) approved","note":"FDA, July 2018, for unresectable MIBG-positive PPGL; later discontinued commercially.","refs":["i131-mibg"]},{"year":2024,"title":"FIRSTMAPPP: sunitinib delays progression","note":"Baudin and colleagues, Lancet: first randomised trial in metastatic PPGL.","refs":["sunitinib"]},{"year":2025,"title":"Belzutifan approved for PPGL","note":"FDA, 14 May 2025, LITESPARK-015 cohort A1; first oral therapy for the disease.","refs":[]}],"pipeline":["lutathera","prrt","sunitinib","cabozantinib"],"openProblems":["No reliable predictor of metastasis at diagnosis: molecular classifiers and SDHB status are being validated.","Withdrawal of 131I-MIBG from the market left a gap that 177Lu-DOTATATE and alpha-emitters are filling.","Sequencing belzutifan, radioligand therapy and kinase inhibitors: no comparative data.","Lifelong surveillance burden for gene carriers, with children of SDHB carriers screened from early childhood."],"route":"/indications/pheochromocytoma-paraganglioma/"}
{"id":"prostate","kind":"indication","name":"Prostate cancer","aka":[],"tldr":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype.","summary":"Prostate cancer is the most common cancer in men in most high-income countries and a spectrum: most PSA-detected disease is indolent and safely watched (ProtecT: ~3% prostate-cancer mortality at 15 years whatever the strategy), while de novo metastatic disease, treated with hormonal doublets and triplets and since 2026 with radioligand therapy added, still has a median survival of about five years, which makes it the second most common cause of cancer death in men. Diagnosis now runs PSA → multiparametric MRI (PRECISION) → targeted biopsy → Grade Group, with germline and somatic HRR testing for advanced disease and PSMA PET for staging (proPSMA) and recurrence. Digital-pathology AI (ArteraAI Prostate, 2025) and gene-expression classifiers (Decipher) refine who needs treatment and who benefits from adding hormone therapy.\n\nTreatment is built on androgen deprivation, the first targeted cancer therapy (Huggins, 1941). Metastatic hormone-sensitive disease is treated with doublets (ADT + abiraterone, enzalutamide, apalutamide or darolutamide) or triplets adding docetaxel (ARASENS, PEACE-1), and since 31 July 2026 with 177Lu-PSMA-617 added to ADT + ARPI (PSMAddition, rPFS HR 0.72). PTEN-deficient disease gained capivasertib + abiraterone in 2026. In castration-resistant disease the sequence includes ARPI switch, PARP inhibitors for HRR-mutant tumours (PROfound, PROpel, TALAPRO-2 with OS benefit), docetaxel and cabazitaxel, radium-223 for bone-only disease, and 177Lu-PSMA-617 before or after chemotherapy (VISION, PSMAfore). Enzalutamide is approved even for high-risk PSA-only recurrence (EMBARK).\n\nProstate cancer is the proving ground for theranostics: PSMA PET selects and PSMA radioligands treat. Competing 177Lu-PSMA-I&T products (SPLASH, ECLIPSE) have improved progression but not yet survival; alpha-emitting 225Ac-PSMA agents are in phase 3 (AlphaBreak, AcTION) and produce responses after lutetium failure. T-cell engagers against STEAP1 (xaluritamig, XALute) and KLK2 (pasritamig) are the first immunotherapies with real activity in a disease that ignores checkpoint inhibitors; EZH2 inhibition (mevrometostat, MEVPRO) aims to re-sensitise to hormonal therapy. The unsolved problems are neuroendocrine transformation, AR-V7-driven resistance (the N-terminal-domain inhibitor masofaniten failed), Ac-225 supply, and the over- versus under-diagnosis tension in screening.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer"}],"tags":["gu","spike"],"related":["radiopharma-roadmap","psma-pet-to-rlt","beta-then-alpha","src-urotoday","lu-177","ac-225","ra-223"],"indications":[],"sections":[],"technologies":["psma-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":["psma","parp","b7h3","dll3","steap1","klk2","grpr"],"drugs":["samarium-153-lexidronam"],"companies":["futurechem","novartis","bayer","pfizer","johnson-johnson","astrazeneca","lantheus","telix","curium"],"institutions":["royal-marsden","peter-mac","ucla-jonsson","johns-hopkins"],"pathways":["prostate-cancer-signalling"],"terms":["biochemical-recurrence","psa50","theranostics","oligometastatic","crossover"],"trials":["nct06855277","nct06780670","mcrpc","nct07311694","nct07615101","nct07649122","nct05381103","pop-rt","nct05939414","nct06520345","nct07052214","nct07611110","nct04557059","nct06235151","nct06754085"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"~1.5 million new cases per year worldwide; lifetime risk ~1 in 8 men in high-income countries; median age at diagnosis 67; most PSA-detected disease is indolent and safely watched. ~400,000 deaths per year worldwide, mostly from disease that was already metastatic at diagnosis.","subtypes":["Localised: low / favourable-intermediate / unfavourable-intermediate / high risk (NCCN)","Non-metastatic castration-resistant (nmCRPC)","Metastatic hormone-sensitive (mHSPC; FDA 2026 term 'androgen pathway modulation-naive or -sensitive'), de novo vs recurrent, high vs low volume (CHAARTED)","Metastatic castration-resistant (mCRPC)","HRR-mutant (~20-25% of mCRPC; BRCA2 most actionable)","PTEN-deficient (~25%)","PSMA-low / heterogeneous (~10%)","Treatment-emergent neuroendocrine prostate cancer (~15-20% of late mCRPC)","Ductal and intraductal / cribriform variants (aggressive)"],"biomarkers":["PSA","Gleason / Grade Group","PSMA PET","HRR genes (BRCA2, ATM, etc.)","PTEN","MSI","AR-V7 (research)","Decipher / ArteraAI","PSA, PSA density, PSA doubling time","Grade Group (Gleason) and cribriform/intraductal pattern","mpMRI PI-RADS score","PSMA PET (SUVmax, total tumour volume) for staging and radioligand eligibility","Germline and somatic HRR genes (BRCA2, BRCA1, ATM, PALB2, CDK12)","PTEN loss (IHC or NGS) for capivasertib","MSI/dMMR (~3%, pembrolizumab)","Decipher genomic classifier; ArteraAI digital pathology","AR-V7 (CTC) in research/limited use","Testosterone level (castration confirmation)","Neuroendocrine markers (chromogranin, synaptophysin, RB1/TP53 loss) on progression"],"standardOfCare":[{"setting":"Localised","approach":"Active surveillance, prostatectomy, or radiation ± ADT (duration guided by risk/ArteraAI).","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Metastatic hormone-sensitive","approach":"ADT + ARPI ± docetaxel; PSMA PET staging; capivasertib if PTEN-deficient.","refs":["psma-pet"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Castration-resistant","approach":"ARPI switch, PARP inhibitor combinations (HRR+), 177Lu-PSMA-617, docetaxel/cabazitaxel, radium-223.","refs":["pluvicto","olaparib","vision","psmafore"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Screening","approach":"Shared-decision PSA testing from 50 (45 if Black or family history/BRCA), risk-adapted intervals; MRI before biopsy; avoid biopsy if MRI negative and PSA density low.","refs":[]},{"setting":"Localised, low / favourable-intermediate risk","approach":"Active surveillance (PSA, MRI, repeat biopsy) for Grade Group 1 and many favourable GG2; genomic classifier or ArteraAI to refine.","refs":[]},{"setting":"Localised, unfavourable-intermediate / high risk","approach":"Radical prostatectomy (robotic) or radiotherapy (hypofractionated IMRT, SBRT, or brachytherapy boost) with 4-6 months (intermediate) to 18-36 months (high risk) of ADT; abiraterone added for very high risk (STAMPEDE); ArteraAI predicts ADT benefit.","refs":["stampede"]},{"setting":"Biochemical recurrence","approach":"PSMA PET to localise; salvage radiotherapy ± ADT after prostatectomy; metastasis-directed SBRT for oligorecurrence (investigational for survival); enzalutamide ± ADT for high-risk BCR (EMBARK).","refs":["psma-pet","biochemical-recurrence","embark","enzalutamide","idea-psma-pet-guided-mdt"]},{"setting":"Metastatic hormone-sensitive (mAPMN/S)","approach":"ADT (GnRH agonist/antagonist, e.g., relugolix) + ARPI (abiraterone, enzalutamide, apalutamide, or darolutamide); add docetaxel for high-volume de novo disease (ARASENS, PEACE-1); add 177Lu-PSMA-617 if PSMA-positive (PSMAddition, approved 31 Jul 2026); capivasertib + abiraterone if PTEN-deficient (2026); prostate RT for low-volume disease.","refs":["abiraterone","enzalutamide","docetaxel","pluvicto","psmaddition"]},{"setting":"Non-metastatic CRPC","approach":"Apalutamide, enzalutamide, or darolutamide (SPARTAN, PROSPER, ARAMIS); PSMA PET usually reclassifies as metastatic.","refs":["enzalutamide","psma-pet"]},{"setting":"Metastatic CRPC, first line","approach":"ARPI (if not used earlier); PARP inhibitor + ARPI for BRCA/HRR-mutant (olaparib-abiraterone, talazoparib-enzalutamide, niraparib-abiraterone); docetaxel; 177Lu-PSMA-617 after one ARPI before chemotherapy (PSMAfore); pembrolizumab if MSI-high.","refs":["olaparib","pluvicto","psmafore","docetaxel","pembrolizumab"]},{"setting":"Metastatic CRPC, later lines","approach":"177Lu-PSMA-617 post-taxane (VISION); cabazitaxel (CARD); radium-223 for bone-only symptomatic disease (with bone protection); 225Ac-PSMA, xaluritamig, pasritamig, mevrometostat in trials; platinum-etoposide for neuroendocrine transformation; tarlatamab/I-DXd trials for DLL3/B7-H3.","refs":["pluvicto","vision","cabazitaxel","radium-223","alsympca","ac225-psma","alphabreak"]}],"stateOfArt":["Theranostic pairing of PSMA PET and Pluvicto.","Genotype-directed doublets.","AI pathology guiding ADT duration.","Radioligand therapy across the metastatic continuum: 177Lu-PSMA-617 approved post-taxane (2022), pre-taxane (2025), and at first metastatic diagnosis with ARPI (31 July 2026).","Triplet therapy (ADT + ARPI + docetaxel) for high-volume de novo disease, with OS HR ~0.7 (ARASENS, PEACE-1).","Genotype-directed doublets: PARP inhibitor + ARPI for HRR-mutant (OS benefit in TALAPRO-2) and capivasertib + abiraterone for PTEN-deficient disease (2026).","Diagnostic pathway rebuilt around MRI-first biopsy and PSMA PET staging; active surveillance is default for low-risk disease.","AI pathology (ArteraAI Prostate) is FDA-authorised to predict who benefits from adding hormone therapy to radiation.","First immunotherapies with real activity: STEAP1 and KLK2 T-cell engagers in phase 3, after checkpoint inhibitors failed in unselected disease."],"history":[{"year":1941,"title":"Huggins: castration controls prostate cancer","refs":[]},{"year":1941,"title":"Huggins shows castration controls metastatic prostate cancer","note":"Nobel Prize 1966; the first hormonal therapy of any cancer.","refs":[]},{"year":1966,"title":"Gleason grading system published","refs":[]},{"year":1986,"title":"PSA test approved for monitoring; screening spreads in the 1990s","refs":[]},{"year":2004,"title":"Docetaxel: first chemotherapy to extend survival (TAX 327)","refs":["docetaxel"]},{"year":2011,"title":"Abiraterone approved","refs":[]},{"year":2011,"title":"Abiraterone approved; enzalutamide follows in 2012","note":"Proof that castration-resistant disease is still AR-driven.","refs":["abiraterone","enzalutamide"]},{"year":2013,"title":"Radium-223: first alpha emitter approved","refs":[]},{"year":2013,"title":"Radium-223: first alpha emitter approved (ALSYMPCA)","refs":["radium-223","alsympca"]},{"year":2015,"title":"CHAARTED and STAMPEDE: docetaxel at first metastatic diagnosis","refs":["chaarted","stampede"]},{"year":2016,"title":"ProtecT validates active surveillance","refs":[]},{"year":2017,"title":"LATITUDE and STAMPEDE: abiraterone in mHSPC","refs":["stampede"]},{"year":2018,"title":"PRECISION: MRI before biopsy","refs":[]},{"year":2020,"title":"PSMA PET approved; olaparib in HRR-mutant mCRPC","refs":["psma-pet","olaparib"]},{"year":2020,"title":"PSMA PET approved; PROfound approves olaparib for HRR-mutant mCRPC","refs":["ga68-psma-11","propsma","olaparib"]},{"year":2021,"title":"VISION: 177Lu-PSMA-617 improves survival; TheraP beats cabazitaxel on response","refs":["vision","therap"]},{"year":2022,"title":"Pluvicto approved","refs":["pluvicto","vision"]},{"year":2022,"title":"Pluvicto approved; ARASENS establishes triplet therapy","refs":["pluvicto"]},{"year":2023,"title":"PARP + ARPI combinations approved (TALAPRO-2, PROpel, MAGNITUDE); EMBARK for biochemical recurrence","refs":["embark"]},{"year":2024,"title":"SPLASH: second PSMA radioligand improves rPFS but not OS","refs":["splash","lu177-psma-it"]},{"year":2025,"title":"ArteraAI Prostate: first predictive AI pathology test","refs":[]},{"year":2025,"title":"Pluvicto pre-chemotherapy (PSMAfore); ArteraAI Prostate FDA-authorised; PSMAddition positive; ECLIPSE positive; masofaniten discontinued","refs":["psmafore","psmaddition","eclipse-psma"]},{"year":2026,"title":"Pluvicto approved in metastatic hormone-sensitive disease (31 July); capivasertib + abiraterone approved for PTEN-deficient disease","refs":["psmaddition","pluvicto"]}],"pipeline":["ac225-psma","aaa817","jnj-87189401","hrs-4357","fpi-2265","alphabreak","lu177-psma-it","eclipse-psma","idea-psma-pet-guided-mdt","idea-alpha-first-mhspc","grpr"],"openProblems":["Overdiagnosis vs. underdiagnosis in screening.","Neuroendocrine transformation.","Ac-225 supply.","Screening trade-off: PSA reduces mortality by ~20% but overdiagnoses; MRI-first and risk-adapted intervals are only partly adopted.","Neuroendocrine / lineage-plastic transformation in ~15-20% of late mCRPC has no targeted therapy; DLL3 and B7-H3 agents are being borrowed from SCLC.","AR-V7 and N-terminal-domain resistance: masofaniten failed; AR degraders remain preclinical/early.","Radioligand sequencing and resistance: 10% PSMA-negative disease, heterogeneity, and no proven therapy after 177Lu failure outside trials; Ac-225 supply is the constraint.","Overall survival has been hard to show for PSMA radioligands beyond VISION (SPLASH, PSMAfore, TheraP confounded by crossover).","Immunotherapy: checkpoint inhibitors fail in unselected disease; engagers bring cytokine release and need outpatient models.","Equity: Black men have ~70% higher incidence and double the mortality yet are under-enrolled in trials; earlier, risk-adapted screening is the lever.","Bone health, cardiovascular risk, and cognitive effects of long-term ADT in men living a decade or more."],"prognosis":{"text":"In the United States, 98.2% of men diagnosed with prostate cancer in 2016-2022 were alive five years later, relative to men of the same age without the disease. For the 69% found while confined to the prostate and the 14% with regional spread, five-year relative survival is 100%; for the 9% found with distant spread it is 40.1%. Most prostate cancers grow slowly, and for many men the question is whether treatment is needed at all rather than whether it will work.","sources":[{"label":"SEER Cancer Stat Facts: Prostate Cancer","url":"https://seer.cancer.gov/statfacts/html/prost.html"}]},"route":"/indications/prostate/"}
{"id":"prostate-bcr","kind":"indication","name":"Biochemical recurrence of prostate cancer","aka":["Biochemically recurrent prostate cancer","PSA recurrence","Rising PSA after local therapy","nmHSPC"],"tldr":"Biochemical recurrence of prostate cancer is a rising PSA after surgery or radiotherapy with nothing yet visible on scans. Salvage radiotherapy can still cure it after surgery, and for a fast-doubling PSA the EMBARK trial showed that enzalutamide with or without hormone therapy delays spread.","summary":"Biochemical recurrence is defined as a PSA of 0.2 ng/mL or more, confirmed, after radical prostatectomy, or a rise of 2 ng/mL above the nadir after radiotherapy (the Phoenix definition). It is found by routine PSA follow-up; PSMA PET now locates the recurrence in most men once PSA passes about 0.5 ng/mL, and often shows disease that conventional imaging misses. After prostatectomy, early salvage radiotherapy to the prostate bed, started before PSA reaches 0.5, cures many men, with short-term hormone therapy added for higher-risk features. After radiotherapy, local salvage by surgery, brachytherapy, cryotherapy or high-intensity focused ultrasound is possible for confirmed local recurrence. Men with a PSA doubling time under nine months are at high risk of metastasis: EMBARK randomised 1,068 such men and showed enzalutamide with leuprolide, or enzalutamide alone, cut metastasis or death by about half compared with leuprolide alone, and the FDA approved enzalutamide for this setting in 2023. Slowly rising PSA can be watched, and PSMA PET-directed stereotactic radiotherapy to a few metastases is under study.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Biochemical_recurrence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biochemical_recurrence"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-high-risk","prostate-nmcrpc","prostate-mhspc"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-kinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-propsma-hofman-lancet-2020"],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"A rising PSA follows a quarter to a third of prostatectomies and radiotherapy courses; only a minority of these men develop metastases on scans within ten years, and the PSA doubling time tells the two apart.","subtypes":["Biochemical recurrence after prostatectomy (PSA 0.2 or more)","Biochemical recurrence after radiotherapy (nadir plus 2)","High-risk biochemical recurrence (PSA doubling time under 9 months, non-metastatic hormone-sensitive)","PSMA PET-detected oligorecurrence"],"biomarkers":["PSA and PSA doubling time","PSMA PET (positive in most men above 0.5 ng/mL)","Decipher on the prostatectomy specimen","Interval from local therapy to recurrence"],"standardOfCare":[{"setting":"After prostatectomy","approach":"Early salvage radiotherapy to the prostate bed, with or without pelvic nodes and four to six months of androgen deprivation for adverse features; observation for slow doubling times.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After radiotherapy, local recurrence","approach":"Salvage prostatectomy, brachytherapy, cryotherapy or high-intensity focused ultrasound in fit men with biopsy-proven local disease and no metastases on PSMA PET.","refs":["psma-pet"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"High-risk biochemical recurrence (doubling time under 9 months)","approach":"Enzalutamide with leuprolide, or enzalutamide alone (EMBARK); PSMA PET before starting; intermittent therapy with treatment suspension when PSA becomes undetectable.","refs":["enzalutamide","embark","psma-pet"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"PSMA PET-detected oligorecurrence","approach":"Stereotactic radiotherapy to the visible metastases, usually within trials or with hormone therapy; the survival benefit is unproven.","refs":["oligometastatic","idea-psma-pet-guided-mdt"]}],"stateOfArt":["PSMA PET has turned biochemical recurrence from an invisible number into a map, though it also finds disease the trials never saw.","EMBARK is the first trial to show that treating a fast-rising PSA with an androgen receptor inhibitor delays metastasis.","Intermittent therapy with a treatment holiday is built into the approved EMBARK regimen."],"history":[{"year":1997,"title":"ASTRO consensus defines PSA failure after radiotherapy","refs":[]},{"year":2005,"title":"Phoenix definition: nadir plus 2 ng/mL","refs":[]},{"year":2017,"title":"RTOG 9601: bicalutamide with salvage radiotherapy improves survival","refs":[]},{"year":2020,"title":"PSMA PET approved for recurrence","refs":["psma-pet"]},{"year":2023,"title":"EMBARK: enzalutamide delays metastasis in high-risk biochemical recurrence","refs":["embark","enzalutamide"]}],"pipeline":["psma-pet","enzalutamide","idea-psma-pet-guided-mdt"],"openProblems":["Whether treating PSMA PET-detected metastases early lengthens life or only lowers PSA.","How to spare men with slow doubling times from years of hormone therapy.","The trials that defined recurrence used conventional imaging; PSMA PET restages many of these men as metastatic."],"parent":"prostate","route":"/indications/prostate-bcr/"}
{"id":"prostate-high-risk","kind":"indication","name":"Localised prostate cancer, high and very high risk","aka":["High-risk prostate cancer","Very high risk prostate cancer","Locally advanced prostate cancer","Grade Group 4 and 5 prostate cancer","Non-metastatic high-risk prostate cancer"],"tldr":"High-risk prostate cancer has Grade Group 4 or 5 disease, a PSA above 20 or a tumour growing beyond the gland. It is still curable, but needs radiotherapy with two to three years of hormone therapy, or surgery followed by radiotherapy, and adding abiraterone to hormone therapy now lengthens life in the highest-risk men.","summary":"High-risk localised prostate cancer is defined by the NCCN as any of clinical stage T3a, Grade Group 4 or 5, or PSA above 20 ng/mL; very high risk adds T3b to T4 disease, primary Gleason pattern 5, more than four cores of Grade Group 4 or 5, or two or more high-risk features. It is found by PSA and biopsy and staged with PSMA PET, which proPSMA showed is far more accurate than CT and bone scan. Standard treatment is external beam radiotherapy to the prostate and pelvic nodes with 18 to 36 months of androgen deprivation, often with a brachytherapy boost, or radical prostatectomy with extended node dissection followed by radiotherapy when the pathology warrants it. STAMPEDE showed that adding two years of abiraterone to androgen deprivation and radiotherapy in men with very high risk or node-positive disease cuts metastasis and death, and this is now guideline care for the highest-risk group. Salvage options after failure are covered under biochemical recurrence.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer_staging"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-bcr","prostate-mhspc"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-propsma-hofman-lancet-2020"],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"About one in five newly diagnosed localised cancers and most of the deaths from disease found before it spreads; ten-year cancer-specific survival is around 85 percent with combined treatment.","subtypes":["High risk (T3a, or Grade Group 4 or 5, or PSA above 20)","Very high risk (T3b to T4, primary pattern 5, more than 4 high-grade cores, or 2 or more high-risk features)","Locally advanced adenocarcinoma with seminal vesicle invasion (T3b)","Clinically node-positive (N1) non-metastatic disease"],"biomarkers":["Gleason Grade Group 4 or 5","PSA above 20 ng/mL","PSMA PET staging","Germline and tumour HRR testing (BRCA2 in particular)","Decipher genomic classifier"],"standardOfCare":[{"setting":"High risk","approach":"External beam radiotherapy to prostate and pelvic nodes with 18 to 36 months of androgen deprivation, with or without brachytherapy boost; or radical prostatectomy with extended lymph node dissection.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Very high risk and node-positive","approach":"Radiotherapy plus androgen deprivation with two years of abiraterone (STAMPEDE); PSMA PET staging before treatment.","refs":["abiraterone","stampede","psma-pet","propsma"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After prostatectomy with adverse pathology","approach":"Adjuvant or early salvage radiotherapy guided by PSA, with hormone therapy for higher-risk features.","refs":["biochemical-recurrence"]}],"stateOfArt":["PSMA PET has replaced bone scan and CT for staging, reclassifying about a quarter of men.","Abiraterone with radiotherapy and hormone therapy is the first drug to improve survival in high-risk non-metastatic disease.","Genomic classifiers and AI pathology are being tested to choose hormone therapy duration."],"history":[{"year":1997,"title":"EORTC 22863: adding three years of hormone therapy to radiotherapy improves survival","refs":[]},{"year":2009,"title":"Long-course beats short-course androgen deprivation with radiotherapy in high-risk disease","refs":[]},{"year":2020,"title":"proPSMA: PSMA PET more accurate than conventional staging","refs":["propsma","psma-pet"]},{"year":2022,"title":"STAMPEDE: abiraterone improves survival in high-risk non-metastatic disease","refs":["stampede","abiraterone"]}],"pipeline":["psma-pet","abiraterone"],"openProblems":["How long hormone therapy should last when abiraterone is added.","Whether PSMA PET-detected nodes should change treatment when the trials were staged conventionally.","Which men with high-risk disease are better served by surgery than radiotherapy."],"parent":"prostate","route":"/indications/prostate-high-risk/"}
{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","aka":["mCRPC","Metastatic CRPC","Castration-resistant metastatic prostate cancer","Hormone-refractory prostate cancer (older term)"],"tldr":"Metastatic castration-resistant prostate cancer is disease that grows despite castrate testosterone. Sequenced treatments now include androgen receptor inhibitors, docetaxel and cabazitaxel, PARP inhibitors for men with BRCA-type mutations, the radioligand 177Lu-PSMA-617 and radium-223 for bone-predominant disease.","summary":"Metastatic castration-resistant prostate cancer is defined by progression on scans or PSA, or new metastases, with castrate testosterone. Nearly every man reaches it from hormone-sensitive disease, and the treatment chosen depends on what he has already had. Men who have not had an androgen receptor pathway inhibitor receive abiraterone or enzalutamide; PROpel, TALAPRO-2 and MAGNITUDE showed that adding olaparib, talazoparib or niraparib helps men with BRCA and other homologous recombination repair mutations, and PROfound showed olaparib alone beats a second hormonal agent in these men. Docetaxel and then cabazitaxel remain the chemotherapies. VISION established 177Lu-PSMA-617 after chemotherapy and PSMAfore moved it before, for PSMA PET-positive disease; 177Lu-PSMA-I&T (SPLASH, ECLIPSE) follows the same path. Radium-223 lengthens life in symptomatic bone-predominant disease without visceral metastases (ALSYMPCA), sipuleucel-T is still approved for minimally symptomatic disease, and pembrolizumab is used for the rare mismatch repair-deficient tumour. Tumour and germline testing for HRR genes and mismatch repair is standard. Actinium-225 PSMA agents, the STEAP1 T-cell engager xaluritamig and the EZH2 inhibitor mevrometostat are in phase 3.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-mhspc","prostate-nmcrpc","prostate-nepc","prostate-bcr","lu-177","ac-225","ra-223"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021","paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"The state in which nearly all prostate cancer deaths occur, about 400,000 a year worldwide; median survival from first treatment is now around three years, longer for men who have not had an androgen receptor inhibitor.","subtypes":["mCRPC, androgen receptor pathway inhibitor-naive","mCRPC after an androgen receptor pathway inhibitor, chemotherapy-naive","mCRPC after taxane chemotherapy","HRR-mutant mCRPC (BRCA1, BRCA2, ATM and others; PARP inhibitors)","PSMA PET-positive mCRPC (radioligand therapy)","Bone-predominant mCRPC without visceral metastases (radium-223)","Mismatch repair-deficient mCRPC (pembrolizumab)"],"biomarkers":["Tumour and germline HRR genes (BRCA2 above all)","PSMA PET uptake and FDG discordance","Mismatch repair deficiency and tumour mutational burden","PSA and alkaline phosphatase","Circulating tumour DNA (AR amplification, BRCA2 reversion)","AR-V7 in circulating tumour cells (research)"],"standardOfCare":[{"setting":"First line, androgen receptor pathway inhibitor-naive","approach":"Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE).","refs":["abiraterone","enzalutamide","olaparib"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After an androgen receptor pathway inhibitor","approach":"Docetaxel; olaparib or rucaparib for BRCA-mutant disease (PROfound); 177Lu-PSMA-617 for PSMA-positive disease before chemotherapy (PSMAfore); pembrolizumab for mismatch repair-deficient tumours.","refs":["docetaxel","olaparib","pluvicto","psmafore","pembrolizumab"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After docetaxel","approach":"177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used.","refs":["pluvicto","vision","cabazitaxel","radium-223","alsympca","therap"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Bone health","approach":"Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Phase 3 options","approach":"Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials.","refs":["ac225-psma","lu177-psma-it","alphabreak","splash","eclipse-psma"]}],"stateOfArt":["PSMA PET and 177Lu-PSMA-617 make prostate cancer the model for theranostics.","PARP inhibitors gave prostate cancer its first genotype-directed treatment.","Survival in this once six-month setting is now measured in years, built from sequenced drugs rather than one breakthrough."],"history":[{"year":2004,"title":"TAX 327: docetaxel is the first drug to lengthen life in castration-resistant disease","refs":["docetaxel"]},{"year":2010,"title":"Cabazitaxel and sipuleucel-T approved","refs":["cabazitaxel"]},{"year":2011,"title":"Abiraterone approved after docetaxel","refs":["abiraterone"]},{"year":2012,"title":"Enzalutamide approved","refs":["enzalutamide"]},{"year":2013,"title":"ALSYMPCA: radium-223, the first alpha emitter","refs":["alsympca","radium-223"]},{"year":2020,"title":"PROfound: olaparib for HRR-mutant disease","refs":["olaparib"]},{"year":2021,"title":"VISION: 177Lu-PSMA-617 lengthens life","refs":["vision","pluvicto"]},{"year":2022,"title":"PROpel and MAGNITUDE: PARP inhibitor plus abiraterone","refs":[]},{"year":2023,"title":"PSMAfore and TALAPRO-2","refs":["psmafore"]},{"year":2025,"title":"ECLIPSE: 177Lu-PSMA-I&T meets its endpoint","refs":["eclipse-psma"]}],"pipeline":["ac225-psma","lu177-psma-it","fpi-2265"],"openProblems":["The best sequence of radioligand, PARP inhibitor and chemotherapy is untested.","Actinium-225 supply and the lack of alpha-emitter dosimetry.","Lineage plasticity to neuroendocrine disease under androgen receptor blockade.","Resistance to 177Lu-PSMA-617 in PSMA-low or FDG-discordant disease."],"parent":"prostate","route":"/indications/prostate-mcrpc/"}
{"id":"prostate-mhspc","kind":"indication","name":"Metastatic hormone-sensitive prostate cancer","aka":["mHSPC","Metastatic castration-sensitive prostate cancer","mCSPC","De novo metastatic prostate cancer","Hormone-naive metastatic prostate cancer"],"tldr":"Metastatic hormone-sensitive prostate cancer is disease that has spread but still responds to lowering testosterone. Hormone therapy alone is no longer enough: adding an androgen receptor inhibitor, and docetaxel for high-volume disease, lengthens life by years.","summary":"Metastatic hormone-sensitive prostate cancer has spread to bone, nodes or organs and has not yet been exposed to, or is still controlled by, androgen deprivation. It is found by PSA, biopsy and imaging, increasingly PSMA PET, and is split into high volume (four or more bone metastases with one outside the spine and pelvis, or visceral disease) and low volume, and into de novo and recurrent disease. Androgen deprivation with a GnRH agonist or antagonist is the backbone. CHAARTED and STAMPEDE showed docetaxel added to it lengthens life, mainly in high-volume disease; LATITUDE and STAMPEDE showed the same for abiraterone; TITAN (apalutamide), ENZAMET and ARCHES (enzalutamide) and ARANOTE (darolutamide) extended the benefit to every androgen receptor pathway inhibitor. PEACE-1 and ARASENS proved triplet therapy with docetaxel plus abiraterone or darolutamide for men fit for chemotherapy with high-volume disease. Radiotherapy to the prostate improves survival in low-volume disease (STAMPEDE). CAPItello-281 added capivasertib for PTEN-deficient tumours in 2026, and PSMAddition brought 177Lu-PSMA-617 into this setting the same year. Hormone therapy alone is now reserved for frail men.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer#Metastatic_disease","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-mcrpc","prostate-nmcrpc","prostate-bcr","prostate-high-risk","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"About one in twenty prostate cancers are metastatic at diagnosis in high-income countries and far more elsewhere; median survival has risen from under four years to more than five with combination therapy.","subtypes":["De novo high-volume mHSPC (4 or more bone metastases or visceral disease)","De novo low-volume mHSPC (oligometastatic, prostate radiotherapy helps)","Recurrent metastatic hormone-sensitive disease after local therapy","PTEN-deficient mHSPC (capivasertib)","PSMA-positive mHSPC (177Lu-PSMA-617)"],"biomarkers":["Disease volume (CHAARTED criteria)","De novo versus recurrent","PTEN loss by immunohistochemistry","PSMA PET positivity","Germline and tumour HRR genes","PSA fall to below 0.2 at seven months (prognostic)"],"standardOfCare":[{"setting":"All patients, backbone","approach":"Continuous androgen deprivation with a GnRH agonist, GnRH antagonist or orchiectomy; never alone in fit men.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Doublet therapy","approach":"Androgen deprivation plus abiraterone (LATITUDE, STAMPEDE), enzalutamide (ARCHES, ENZAMET), apalutamide (TITAN) or darolutamide (ARANOTE).","refs":["abiraterone","enzalutamide","stampede"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Triplet therapy, high volume, fit for chemotherapy","approach":"Androgen deprivation plus docetaxel plus darolutamide (ARASENS) or abiraterone (PEACE-1).","refs":["docetaxel","abiraterone","chaarted"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Low-volume disease","approach":"Doublet therapy plus radiotherapy to the prostate (STAMPEDE); metastasis-directed radiotherapy within trials.","refs":["stampede","oligometastatic"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Biomarker-selected additions (2026)","approach":"Capivasertib with abiraterone for PTEN-deficient tumours (CAPItello-281); 177Lu-PSMA-617 with androgen receptor pathway inhibitor for PSMA-positive disease (PSMAddition).","refs":["pluvicto","psmaddition"]}],"stateOfArt":["Combination therapy from diagnosis has lifted median survival past five years, and past eight in low-volume disease.","Triplet therapy is standard for high-volume disease in men fit for docetaxel.","The first biomarker-selected drugs, capivasertib and 177Lu-PSMA-617, entered this setting in 2026."],"history":[{"year":1941,"title":"Huggins shows castration controls metastatic prostate cancer","refs":[]},{"year":2015,"title":"CHAARTED: docetaxel with hormone therapy lengthens life","refs":["chaarted","docetaxel"]},{"year":2016,"title":"STAMPEDE confirms docetaxel at first diagnosis","refs":["stampede"]},{"year":2017,"title":"LATITUDE and STAMPEDE: abiraterone at first diagnosis","refs":["stampede","abiraterone"]},{"year":2019,"title":"TITAN, ENZAMET and ARCHES: androgen receptor inhibitors for all","refs":["enzalutamide"]},{"year":2021,"title":"PEACE-1: European triplet therapy","refs":[]},{"year":2022,"title":"ARASENS: darolutamide triplet cuts death by a third","refs":[]},{"year":2026,"title":"Capivasertib for PTEN-deficient and 177Lu-PSMA-617 for PSMA-positive disease approved","refs":["psmaddition","pluvicto"]}],"pipeline":["pluvicto","psmaddition","psma-pet"],"openProblems":["Who needs triplet therapy and who is overtreated by it.","Whether intermittent or de-escalated therapy is safe after a deep PSA response.","PSMA PET restages many men the trials called non-metastatic, and the evidence has not caught up."],"parent":"prostate","route":"/indications/prostate-mhspc/"}
{"id":"prostate-nepc","kind":"indication","name":"Neuroendocrine and small-cell prostate cancer","aka":["NEPC","Treatment-emergent neuroendocrine prostate cancer","t-NEPC","Small-cell carcinoma of the prostate","Aggressive variant prostate cancer"],"tldr":"Neuroendocrine prostate cancer is a form that has stopped depending on the androgen receptor, either from the start or after years of hormone therapy. It no longer shows up on PSA, spreads to the liver and brain, and is treated with the platinum chemotherapy used for small-cell lung cancer.","summary":"Neuroendocrine prostate cancer includes rare de novo small-cell carcinoma and, far more often, treatment-emergent disease that arises when adenocarcinoma under prolonged androgen receptor blockade switches lineage, typically with combined loss of RB1 and TP53, PTEN loss, MYCN or AURKA amplification and loss of androgen receptor and PSA expression. It is suspected when disease progresses with a low or flat PSA, visceral or lytic bone metastases, raised chromogranin, neuron-specific enolase or lactate dehydrogenase, or FDG-avid but PSMA-negative lesions, and confirmed by biopsy showing small-cell morphology or synaptophysin and chromogranin staining. There is no approved therapy specific to it: platinum with etoposide, or carboplatin with docetaxel for mixed histology, is standard, with response rates of about half but brief duration, and androgen deprivation is usually continued. Immunotherapy adds little outside mismatch repair deficiency. DLL3 is expressed in most neuroendocrine prostate cancers, and the DLL3 T-cell engager tarlatamab, approved for small-cell lung cancer, is in trials here; EZH2 inhibitors and aurora kinase inhibitors are being tested against the lineage switch itself.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-mcrpc","prostate-mhspc","prostate-nmcrpc"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"Pure small-cell prostate cancer is under 1 percent of new diagnoses, but neuroendocrine features emerge in 10 to 20 percent of men treated with potent androgen receptor inhibitors; median survival after diagnosis is about a year.","subtypes":["De novo small-cell carcinoma of the prostate","Treatment-emergent neuroendocrine prostate cancer (after androgen receptor pathway inhibitors)","Mixed adenocarcinoma and neuroendocrine carcinoma","Aggressive variant prostate cancer (clinical definition, low PSA, visceral spread)","Large-cell neuroendocrine carcinoma of the prostate"],"biomarkers":["Synaptophysin, chromogranin and INSM1 staining","Loss of androgen receptor and PSA expression","Combined RB1 and TP53 loss","MYCN and AURKA amplification","DLL3 expression","Serum chromogranin A, neuron-specific enolase and lactate dehydrogenase","FDG PET-avid, PSMA PET-negative lesions"],"standardOfCare":[{"setting":"Small-cell or predominantly neuroendocrine","approach":"Cisplatin or carboplatin with etoposide, as for small-cell lung cancer; continue androgen deprivation; brain imaging.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Mixed adenocarcinoma and neuroendocrine, or aggressive variant","approach":"Carboplatin plus docetaxel or cabazitaxel, then platinum with etoposide; clinical trial enrolment preferred.","refs":["docetaxel","cabazitaxel"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Recognition and biopsy","approach":"Biopsy any progression with low PSA, visceral metastases or PSMA-negative FDG-avid lesions; test for mismatch repair deficiency (pembrolizumab) and HRR genes.","refs":["psma-pet","pet","pembrolizumab"]},{"setting":"Trials","approach":"DLL3 T-cell engagers (tarlatamab), EZH2 inhibitors and aurora kinase inhibitors against the lineage switch; lurbinectedin borrowed from small-cell lung cancer.","refs":["dll3"]}],"stateOfArt":["Sequencing has shown that neuroendocrine prostate cancer evolves from the same clone as the adenocarcinoma rather than arising anew.","DLL3 gives the disease its first surface target, borrowed from small-cell lung cancer.","Lineage plasticity is now studied as a drug target in its own right."],"history":[{"year":1977,"title":"Small-cell carcinoma of the prostate first described","refs":["sclc"]},{"year":2011,"title":"Beltran finds AURKA and MYCN amplification in neuroendocrine prostate cancer","refs":[]},{"year":2016,"title":"Divergent clonal evolution from adenocarcinoma shown by sequencing","refs":[]},{"year":2017,"title":"RB1 and TP53 loss drive lineage plasticity in models","refs":[]},{"year":2018,"title":"Aggarwal: 17 percent of men on potent hormone therapy have neuroendocrine features at biopsy","refs":[]},{"year":2024,"title":"Tarlatamab shows activity against DLL3-positive neuroendocrine prostate cancer","refs":["dll3"]}],"pipeline":[],"openProblems":["No approved therapy specific to the disease; every regimen is borrowed from lung cancer.","No blood test reliably detects the lineage switch before it shows on scans.","Whether androgen receptor blockade should be de-escalated to slow the switch."],"parent":"prostate","route":"/indications/prostate-nepc/"}
{"id":"prostate-nmcrpc","kind":"indication","name":"Non-metastatic castration-resistant prostate cancer","aka":["nmCRPC","M0 CRPC","Non-metastatic CRPC","Rising PSA on hormone therapy without metastases"],"tldr":"Non-metastatic castration-resistant prostate cancer is a PSA that keeps rising on hormone therapy while scans still show nothing. Three androgen receptor blockers, apalutamide, enzalutamide and darolutamide, each delay metastasis by about two years and lengthen life, and darolutamide is the gentlest.","summary":"Non-metastatic castration-resistant prostate cancer is defined by a rising PSA with castrate testosterone (below 50 ng/dL) and no metastases on CT and bone scan. It is found in men on long-term androgen deprivation, and the risk is judged by PSA doubling time: under ten months marks high risk. Three trials in men with a doubling time of ten months or less changed care in 2018 and 2019: SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide) each roughly doubled metastasis-free survival, from about 16 to 18 months to 36 to 40 months, and each later showed longer overall survival, so all three are approved. Darolutamide crosses into the brain least and causes the fewest falls, fractures and cognitive effects. Men with a slow doubling time can be observed on hormone therapy. PSMA PET now finds metastases in most of these men, which moves them into metastatic castration-resistant disease on paper without changing their biology, so guidelines still treat by the conventional imaging that the trials used.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":["prostate-bcr","prostate-mhspc","prostate-mcrpc"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-kinetics"],"trials":["prosper"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"A shrinking group, because PSMA PET reveals metastases in most men once called non-metastatic; about a third with a PSA doubling time under ten months developed visible metastases within two years on hormone therapy alone.","subtypes":["High-risk nmCRPC (PSA doubling time 10 months or less)","Low-risk nmCRPC (slow PSA doubling time, observation)","PSMA PET-positive, conventional imaging-negative castration-resistant disease"],"biomarkers":["Castrate testosterone (below 50 ng/dL)","PSA doubling time","Conventional imaging negative","PSMA PET (often positive)","AR alterations and AR-V7 (research)"],"standardOfCare":[{"setting":"High-risk nmCRPC (doubling time 10 months or less)","approach":"Continue androgen deprivation and add apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS); darolutamide preferred when falls or cognition are concerns.","refs":["enzalutamide"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Low-risk nmCRPC","approach":"Observation on androgen deprivation with PSA monitoring and imaging; first-generation antiandrogen or its withdrawal as older options.","refs":[],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Staging","approach":"PSMA PET locates disease in most men; conventional imaging still defines the setting the trials studied.","refs":["psma-pet","mcrpc-mhspc"]}],"stateOfArt":["Three androgen receptor inhibitors, each proven in its own trial, give men a choice weighted by side effects.","Metastasis-free survival was accepted by regulators as a surrogate endpoint on the strength of these trials.","PSMA PET is dissolving the category from the inside."],"history":[{"year":2012,"title":"Metastasis-free survival validated as a surrogate for survival in prostate cancer","refs":[]},{"year":2018,"title":"SPARTAN and PROSPER: apalutamide and enzalutamide approved for nmCRPC","refs":["enzalutamide"]},{"year":2019,"title":"ARAMIS: darolutamide approved for nmCRPC","refs":[]},{"year":2020,"title":"All three trials report longer overall survival","refs":["enzalutamide"]}],"pipeline":["psma-pet"],"openProblems":["Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic.","Cost and side effects of years of androgen receptor inhibition in men without symptoms.","No trial compares the three drugs head to head."],"parent":"prostate","route":"/indications/prostate-nmcrpc/"}
{"id":"rcc","kind":"indication","name":"Renal cell carcinoma","aka":["RCC"],"tldr":"Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan.","summary":"Renal cell carcinoma is a cancer of the kidney's tubules, increasingly found by chance on scans done for other reasons. Three quarters are clear-cell tumours defined by loss of the VHL gene, which leaves the oxygen-sensing HIF-2α switch permanently on and makes the tumour intensely vascular and immune-infiltrated. That biology explains the whole modern treatment story: anti-VEGF pills (2005-2012), immunotherapy (2015 onward), their combination (2018 onward), and the first HIF-2α inhibitor, belzutifan (2021).\n\nFor metastatic disease, four immunotherapy-based first-line regimens have survival benefit: nivolumab-ipilimumab (CheckMate 214, durable remissions in a fifth of intermediate/poor-risk patients, still visible at eight years) and three IO-TKI doublets (pembrolizumab-axitinib, nivolumab-cabozantinib, lenvatinib-pembrolizumab). Attempts to do better in first line with triplets failed on survival (COSMIC-313) or fell short (LITESPARK-012), and two trials (CONTACT-03, TiNivo-2) showed that restarting immunotherapy after it fails does not help. After surgery, adjuvant pembrolizumab (KEYNOTE-564) was the first adjuvant immunotherapy in any solid tumour to improve overall survival, and in 2026 belzutifan plus pembrolizumab (LITESPARK-022) became the first adjuvant combination, though three other adjuvant immunotherapy trials were negative.\n\nWhat comes next: selecting who needs adjuvant therapy (ctDNA is weak in RCC; CAIX PET and gene signatures are candidates); CAIX theranostics with radiolabelled girentuximab; zanzalintinib and next-generation TKIs; HIF-2α combinations in the right setting; CD70 and CAIX cell therapies; treatment-free survival as an endpoint; and better management of the small renal masses that make up an increasing share of diagnoses, many of which need no treatment at all. Non-clear-cell histologies (papillary, chromophobe, translocation) remain under-served.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Renal_cell_carcinoma","links":[{"label":"NCI PDQ: renal cell cancer treatment","url":"https://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq"},{"label":"CheckMate 214 8-year follow-up","url":"https://www.annalsofoncology.org/article/S0923-7534(24)01516-3/fulltext"}],"tags":["gu"],"related":["src-urotoday"],"indications":[],"sections":[],"technologies":["caix-pet","radioimmunotherapy"],"targets":[],"drugs":[],"companies":["bms","merck","pfizer","novartis","telix"],"institutions":["mskcc","md-anderson","dana-farber"],"pathways":["hif-vhl"],"terms":["oligometastatic"],"trials":["nct07197580"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"Renal cell carcinoma causes about 430,000 cases a year worldwide, with incidence rising as imaging finds more small tumours, many of which need no treatment; ~20-30% are metastatic at diagnosis, and immunotherapy doublets now give durable remissions in about a fifth of those patients. ~180,000 deaths a year; registry five-year survival for metastatic disease is ~15% overall, higher with modern IO regimens.","subtypes":["Clear-cell (~75%; VHL loss, HIF-2α driven)","Papillary type 1 (MET) and type 2 (FH, others)","Chromophobe","Translocation (TFE3/TFEB)","Collecting duct and medullary (SMARCB1)","Sarcomatoid differentiation (any histology, ~10%)","Hereditary syndromes: VHL, HLRCC (FH), BHD (FLCN), HPRC (MET)"],"biomarkers":["Clear-cell vs non-clear-cell histology","VHL","IMDC risk","CAIX (imaging, 89Zr-girentuximab)","IMDC risk group (six clinical factors)","Histology and sarcomatoid features","VHL / HIF-2α axis (belzutifan)","PD-L1 (not used for selection)","CAIX (imaging; theranostic target)","CD70 (CAR-T target)","MET (papillary type 1)","Gene-expression signatures (angiogenesis vs T-effector; research)","ctDNA (low shedding; research)"],"standardOfCare":[{"setting":"Localised","approach":"Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.","refs":["pembrolizumab"],"guideline":{"version":"NCCN Guidelines: Kidney Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440"}},{"setting":"Metastatic","approach":"IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.","refs":["pembrolizumab"],"guideline":{"version":"NCCN Guidelines: Kidney Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1440"}},{"setting":"Small renal mass (<4 cm)","approach":"Active surveillance, partial nephrectomy (usually robotic), or thermal ablation depending on growth, comorbidity, and biopsy; renal mass biopsy increasingly used.","refs":[],"guideline":{"nccn":"2A","version":"NCCN Kidney v3.2026"}},{"setting":"Localised T1b-T3","approach":"Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.","refs":[],"guideline":{"nccn":"1 (surgery)"}},{"setting":"High-risk after nephrectomy (clear-cell)","approach":"Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.","refs":["pembrolizumab"],"guideline":{"nccn":"1 (pembrolizumab)","esmoMcbs":"A"}},{"setting":"Metastatic, intermediate/poor risk, first line","approach":"Nivolumab + ipilimumab, or an IO-TKI doublet (pembrolizumab + axitinib, nivolumab + cabozantinib, lenvatinib + pembrolizumab); cytoreductive nephrectomy deferred or omitted (CARMENA) except in selected cases.","refs":["pembrolizumab","cabozantinib"],"guideline":{"nccn":"1 (preferred: all four regimens)","esmoMcbs":"4"}},{"setting":"Metastatic, favourable risk, first line","approach":"IO-TKI doublet (PFS benefit; OS benefit unproven in this group) or single-agent TKI (sunitinib, pazopanib) with deferred IO; active surveillance for indolent low-volume disease.","refs":["pembrolizumab","cabozantinib","sunitinib"],"guideline":{"nccn":"1 (IO-TKI); 2A (TKI alone)"}},{"setting":"Second line after IO-based therapy","approach":"Single-agent TKI (cabozantinib, axitinib, lenvatinib + everolimus, tivozanib); belzutifan after both IO and VEGF-TKI (LITESPARK-005). Do not rechallenge PD-1 (CONTACT-03, TiNivo-2).","refs":["cabozantinib","everolimus"],"guideline":{"nccn":"1 (cabozantinib, belzutifan)"}},{"setting":"Oligometastatic / oligoprogressive disease","approach":"Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.","refs":[],"guideline":{"nccn":"2A"}},{"setting":"Non-clear-cell RCC","approach":"Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.","refs":["cabozantinib","pembrolizumab"],"guideline":{"nccn":"2A"}},{"setting":"VHL disease","approach":"Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).","refs":[],"guideline":{"nccn":"1"}}],"stateOfArt":["Adjuvant immunotherapy with OS benefit.","HIF-2α inhibition.","Four immunotherapy-based first-line regimens with survival benefit; durable remissions off treatment in ~20% with nivolumab-ipilimumab at 8 years.","Adjuvant pembrolizumab improves overall survival (KEYNOTE-564); pembrolizumab + belzutifan approved as adjuvant combination (2026).","Belzutifan validates HIF-2α as a target in VHL disease and pretreated RCC.","Two negative rechallenge trials (CONTACT-03, TiNivo-2) and two failed first-line intensification trials (COSMIC-313, LITESPARK-012) have sharpened the algorithm rather than widened it.","Active surveillance and nephron-sparing approaches are standard for small renal masses.","CAIX PET (ZIRCON) offers non-invasive diagnosis of clear-cell RCC; approval delayed by a 2025 CRL."],"history":[{"year":1992,"title":"High-dose IL-2 approved","refs":[]},{"year":1992,"title":"High-dose IL-2 approved: first immunotherapy for RCC, with rare cures","refs":[]},{"year":1993,"title":"VHL gene identified; the molecular basis of clear-cell RCC","refs":[]},{"year":2001,"title":"Cytoreductive nephrectomy improves survival with interferon (SWOG 8949)","refs":[]},{"year":2005,"title":"Sorafenib/sunitinib: VEGF era","refs":[]},{"year":2005,"title":"Sorafenib approved: first VEGF-pathway TKI in RCC","refs":[]},{"year":2006,"title":"Sunitinib approved; replaces interferon","refs":["sunitinib"]},{"year":2009,"title":"Everolimus approved second line (RECORD-1)","refs":["everolimus"]},{"year":2012,"title":"Axitinib approved (AXIS)","refs":[]},{"year":2015,"title":"Nivolumab beats everolimus (CheckMate 025): immunotherapy returns to RCC","refs":[]},{"year":2016,"title":"Cabozantinib approved (METEOR)","refs":["cabozantinib"]},{"year":2018,"title":"Nivolumab-ipilimumab first line","refs":[]},{"year":2018,"title":"Nivolumab-ipilimumab first line (CheckMate 214); CARMENA questions cytoreductive nephrectomy","refs":[]},{"year":2019,"title":"Pembrolizumab-axitinib and avelumab-axitinib: IO-TKI era begins","refs":[]},{"year":2021,"title":"Belzutifan approved","refs":[]},{"year":2021,"title":"Nivolumab-cabozantinib, lenvatinib-pembrolizumab, adjuvant pembrolizumab, belzutifan (VHL), tivozanib approved","refs":[]},{"year":2023,"title":"COSMIC-313 triplet fails on OS; CONTACT-03 closes IO rechallenge; belzutifan approved after IO/TKI (LITESPARK-005); ZIRCON validates CAIX PET","refs":["caix-pet"]},{"year":2024,"title":"KEYNOTE-564 shows OS benefit; CheckMate 214 8-year data; TiNivo-2 negative","refs":[]},{"year":2026,"title":"LITESPARK-022 positive and approved (adjuvant belzutifan + pembrolizumab); LITESPARK-012 first-line triplet falls short","refs":[]}],"pipeline":["caix-pet","idea-caix-theranostics","radioimmunotherapy"],"openProblems":["Non-clear-cell histologies understudied.","No validated predictive biomarker for IO.","No predictive biomarker to choose between IO-IO and IO-TKI, or to identify the 20% who achieve durable remission.","Adjuvant therapy treats many who would never relapse; ctDNA shedding is too low for standard MRD approaches.","Favourable-risk disease has no proven OS benefit from any first-line combination.","Non-clear-cell histologies lack dedicated phase 3 evidence.","First-line intensification (triplets) has failed twice; the next step in first line is unclear.","Treatment-free survival and de-escalation after deep response are unstudied prospectively.","Toxicity and dose reductions with lenvatinib-pembrolizumab limit real-world durability.","Small renal mass overtreatment and the absence of a reliable non-invasive diagnostic (CAIX PET awaits approval)."],"prognosis":{"text":"In the United States, 79.2% of people diagnosed with kidney or renal pelvis cancer in 2016-2022 were alive five years later, relative to people of the same age without the disease. Two thirds (66%) are found while confined to the kidney, often incidentally on a scan for something else, with five-year relative survival of 93.6%; it is 77.6% for regional disease (17% of cases) and 20.3% for distant disease (15% of cases). The distant-stage figure only partly reflects the immunotherapy combinations that became first-line treatment during this period.","sources":[{"label":"SEER Cancer Stat Facts: Kidney and Renal Pelvis Cancer","url":"https://seer.cancer.gov/statfacts/html/kidrp.html"}]},"route":"/indications/rcc/"}
{"id":"sclc","kind":"indication","name":"Small-cell lung cancer","aka":[],"tldr":"A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle.","summary":"Small-cell lung cancer is a high-grade neuroendocrine carcinoma, almost always caused by smoking, defined by near-universal loss of TP53 and RB1 and by explosive growth. It presents as extensive-stage disease in two thirds of patients, responds to chemotherapy in most, and relapses in almost all. For three decades the treatment was platinum-etoposide, thoracic radiotherapy for limited-stage disease, prophylactic cranial irradiation, and topotecan at relapse.\n\nThe field moved in three steps. First-line chemo-immunotherapy (IMpower133 2018, CASPIAN 2019, ASTRUM-005 2022) added two to five months of median survival and a small tail of long-term survivors. Consolidation durvalumab after chemoradiotherapy for limited-stage disease (ADRIATIC, approved December 2024) was the first curative-intent advance in 30 years, lifting median survival to nearly five years. In relapsed disease, tarlatamab, the DLL3 T-cell engager, became the first drug to beat chemotherapy on overall survival (DeLLphi-304; full FDA approval November 2025), and lurbinectedin plus atezolizumab became the first approved first-line maintenance regimen (IMforte, October 2025).\n\nWhat is next: maintenance intensification with tarlatamab (DeLLphi-305), the B7-H3 ADC ifinatamab deruxtecan in second line (IDeate-Lung02), alpha-emitting SSTR radioligands (RYZ101), subtype-directed therapy (ASCL1, NEUROD1, POU2F3, inflamed), bispecific and trispecific DLL3 engagers, and the settled question of whether MRI surveillance can replace prophylactic cranial irradiation. Screening remains limited to low-dose CT in smokers, which detects few small-cell cancers early.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Small-cell_carcinoma","links":[{"label":"NCI PDQ: small cell lung cancer treatment","url":"https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq"},{"label":"IASLC: tarlatamab first-line maintenance data","url":"https://www.iaslc.org/iaslc-news/press-release/tarlatamab-anti-pd-l1-first-line-maintenance-after-chemo-immunotherapy-es"}],"tags":["lung"],"related":[],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["dll3","b7h3","sstr2","parp"],"drugs":[],"companies":["astrazeneca","merck","bms"],"institutions":["mskcc","md-anderson","dana-farber"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"lung","burden":"Small-cell lung cancer makes up about 15% of lung cancers, roughly 250,000 cases a year worldwide, almost entirely in current or former smokers. Limited-stage disease is treated with curative intent and now with durvalumab consolidation. Median survival is nearly five years in limited-stage and about one year in extensive-stage disease.","subtypes":["Limited-stage (one hemithorax, ~30%)","Extensive-stage (~70%)","SCLC-A (ASCL1-driven, DLL3-high; ~50%)","SCLC-N (NEUROD1)","SCLC-P (POU2F3, tuft-cell-like)","SCLC-I (inflamed, IO-responsive)","Transformed SCLC (from EGFR-mutant NSCLC under TKI)","Combined small-cell / non-small-cell histology"],"biomarkers":["DLL3 (not required for tarlatamab)","B7-H3","SCLC-A/N/P/I subtypes (research)","Stage (limited vs extensive) is the dominant decision","B7-H3 (I-DXd trials)","SSTR2 (RYZ101)","Transcription-factor subtype (ASCL1/NEUROD1/POU2F3/YAP1, research)","PD-L1 and TMB (not predictive in SCLC)","SLFN11 (chemotherapy/PARP sensitivity, research)","ctDNA (research)"],"standardOfCare":[{"setting":"Limited stage","approach":"Chemoradiation → durvalumab; prophylactic cranial irradiation or MRI surveillance.","refs":["durvalumab"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"Extensive stage","approach":"Platinum-etoposide + atezolizumab/durvalumab; lurbinectedin + atezolizumab maintenance.","refs":["durvalumab"],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"Relapsed","approach":"Tarlatamab (preferred), lurbinectedin, topotecan; I-DXd in trials.","refs":[],"guideline":{"version":"NCCN Guidelines: Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462"}},{"setting":"Screening and diagnosis","approach":"Low-dose CT screening in heavy smokers finds some SCLC but stage shift is limited; diagnosis by bronchoscopic or CT-guided biopsy; staging with PET/CT and brain MRI.","refs":["ct","pet-ct"],"guideline":{"nccn":"SCLC guideline, staging workup","version":"NCCN SCLC v2.2026"}},{"setting":"Very limited stage (T1-2 N0, ~5%)","approach":"Lobectomy with mediastinal node dissection or SBRT, followed by adjuvant platinum-etoposide; PCI or MRI surveillance.","refs":[],"guideline":{"nccn":"2A"}},{"setting":"Limited stage","approach":"Concurrent cisplatin-etoposide with thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily), then durvalumab consolidation up to 2 years (ADRIATIC); PCI or MRI surveillance.","refs":["durvalumab"],"guideline":{"nccn":"1 (durvalumab consolidation, category 1)","esmoMcbs":"A","version":"NCCN SCLC v2.2026"}},{"setting":"Extensive stage, first line","approach":"Carboplatin-etoposide plus atezolizumab or durvalumab (4 cycles), then maintenance immunotherapy; lurbinectedin added to atezolizumab maintenance since 2025 (IMforte). Serplulimab-chemotherapy where approved. Consolidative thoracic radiotherapy for residual thoracic disease in good responders.","refs":["durvalumab"],"guideline":{"nccn":"1 (chemo-IO); 2A (lurbinectedin maintenance)","esmoMcbs":"3"}},{"setting":"Relapsed, platinum-sensitive (≥90 days)","approach":"Tarlatamab (preferred, OS benefit); platinum-etoposide rechallenge; lurbinectedin; topotecan.","refs":[],"guideline":{"nccn":"1 (tarlatamab)","esmoMcbs":"4"}},{"setting":"Relapsed, platinum-resistant (<90 days)","approach":"Tarlatamab; lurbinectedin; topotecan; clinical trials (I-DXd, RYZ101, DLL3 bispecifics).","refs":["ryz101"],"guideline":{"nccn":"1 (tarlatamab)"}},{"setting":"Brain metastases","approach":"Whole-brain radiotherapy or, increasingly, stereotactic radiosurgery for limited numbers of lesions; PCI decisions individualised.","refs":[]},{"setting":"Transformed SCLC (from EGFR-mutant NSCLC)","approach":"Platinum-etoposide, often with continued EGFR TKI; immunotherapy benefit uncertain; trials.","refs":[]}],"stateOfArt":["Tarlatamab: first OS improvement in relapsed SCLC in decades.","Immunotherapy consolidation in limited stage.","Limited-stage: chemoradiation followed by durvalumab consolidation (ADRIATIC), median OS approaching five years.","Extensive-stage first line: chemo-immunotherapy, now with lurbinectedin-atezolizumab maintenance (IMforte, 2025).","Relapse: tarlatamab (DLL3×CD3) improved OS over chemotherapy (DeLLphi-304) and received full approval in November 2025.","B7-H3 ADC ifinatamab deruxtecan and alpha-emitting SSTR radioligand RYZ101 are in phase 3.","MRI surveillance is displacing prophylactic cranial irradiation while the definitive trial (SWOG S1827) reads out.","Molecular subtypes (A/N/P/I) explain heterogeneity and are moving toward prospective use."],"history":[{"year":1973,"title":"VA Lung Study Group defines limited vs extensive stage","refs":[]},{"year":1980,"title":"Platinum-etoposide becomes standard","refs":[]},{"year":1985,"title":"Platinum-etoposide becomes the standard regimen","refs":[]},{"year":1992,"title":"Meta-analysis: thoracic radiotherapy improves survival in limited-stage disease","refs":[]},{"year":1996,"title":"Topotecan approved for relapsed disease","refs":[]},{"year":1999,"title":"Prophylactic cranial irradiation improves survival in complete responders","refs":[]},{"year":1999,"title":"Twice-daily 45 Gy (Turrisi) sets the limited-stage radiotherapy standard","refs":[]},{"year":2017,"title":"CONVERT: once-daily 66 Gy not superior to twice-daily 45 Gy","refs":[]},{"year":2017,"title":"Japanese trial: PCI gives no survival benefit in extensive-stage disease with MRI surveillance","refs":[]},{"year":2018,"title":"IMpower133: first immunotherapy OS benefit","refs":[]},{"year":2018,"title":"IMpower133: first survival gain in decades with atezolizumab","refs":[]},{"year":2019,"title":"Rovalpituzumab tesirine (first DLL3 ADC) fails","refs":[]},{"year":2019,"title":"Rovalpituzumab tesirine (first DLL3 ADC) fails","refs":["dll3"]},{"year":2019,"title":"CASPIAN confirms chemo-immunotherapy with durvalumab","refs":["durvalumab"]},{"year":2020,"title":"Lurbinectedin accelerated approval in relapsed SCLC","refs":[]},{"year":2021,"title":"SCLC molecular subtypes (A, N, P, I) proposed","refs":[]},{"year":2024,"title":"Tarlatamab approved","refs":[]},{"year":2024,"title":"Tarlatamab accelerated approval; ADRIATIC changes limited-stage care","refs":[]},{"year":2025,"title":"DeLLphi-304 OS benefit and full approval of tarlatamab; IMforte maintenance approved","refs":[]},{"year":2026,"title":"Phase 3 readouts pending for I-DXd and tarlatamab maintenance","refs":[]}],"pipeline":["ryz101","targeted-alpha-therapy"],"openProblems":["Rapid chemoresistance.","Brain metastases.","No screening beyond CT for smokers.","Extensive-stage disease almost always relapses after first-line therapy, so maintenance (lurbinectedin-atezolizumab, tarlatamab) is the current lever; median survival is still barely over a year.","No validated predictive biomarker for immunotherapy benefit; PD-L1 and TMB do not work in SCLC.","Sequencing of tarlatamab, I-DXd, lurbinectedin, and platinum rechallenge is untested.","Cytokine release syndrome and neurotoxicity of T-cell engagers require inpatient step-up dosing that many community centres cannot provide.","Prophylactic cranial irradiation versus MRI surveillance remains unresolved until SWOG S1827 reads out.","Transformed SCLC arising from EGFR-mutant NSCLC has no dedicated evidence base.","Screening rarely catches SCLC early; prevention is tobacco control.","Trials rarely enrol patients with poor performance status, who are common in this disease."],"route":"/indications/sclc/"}
{"id":"small-intestinal-net","kind":"indication","name":"Small intestinal neuroendocrine tumours","aka":["Midgut neuroendocrine tumour","Small bowel NET","Ileal carcinoid","Jejunoileal neuroendocrine tumour","SI-NET"],"tldr":"Small intestinal neuroendocrine tumours are slow-growing hormone-producing tumours of the ileum and jejunum, often found only after they have spread to lymph nodes and the liver. Monthly somatostatin analogue injections control symptoms and growth, lutetium-177 dotatate is the main second treatment, and everolimus, cabozantinib and surgery fill in.","summary":"Small intestinal neuroendocrine tumours arise from enterochromaffin cells of the distal jejunum and ileum, are often multiple along the same segment, and stay small while their mesenteric node metastases and the fibrosis around them grow large enough to kink the bowel and its blood supply. Most are well differentiated with a low Ki-67 index, nearly all express somatostatin receptor 2, and about a fifth to a third of patients with liver metastases develop carcinoid syndrome from serotonin that escapes the liver's first-pass clearance; years of exposure can scar the right-sided heart valves. Diagnosis rests on somatostatin receptor PET, chromogranin A and 24-hour urinary 5-HIAA, and the grade is read from Ki-67 and mitotic count on biopsy.\n\nThe treatment sequence was built by a short chain of trials. PROMID (Journal of Clinical Oncology 2009) randomised 85 patients with treatment-naive metastatic midgut tumours to octreotide LAR or placebo and lengthened time to progression from 6.0 to 14.3 months, the first proof that a somatostatin analogue slows growth as well as symptoms; CLARINET (New England Journal of Medicine 2014) did the same for lanreotide across enteropancreatic tumours, with the median progression-free survival not reached against 18.0 months on placebo. NETTER-1 (New England Journal of Medicine 2017) then randomised 231 patients with midgut tumours progressing on octreotide to lutetium-177 dotatate with octreotide or to high-dose octreotide; 65.2 percent against 10.8 percent were progression-free at 20 months, responses rose from 3 to 18 percent, and the final analysis gave median overall survival of 48.0 against 36.3 months, a difference that did not reach statistical significance because of crossover. Lutathera was approved in 2018, and NETTER-2 (Lancet 2024) moved it to first line for grade 2 and 3 tumours with a Ki-67 of 10 percent or more, lengthening progression-free survival from 8.5 to 22.8 months. Everolimus earned its gut indication in RADIANT-4 (Lancet 2016), where progression-free survival was 11.0 against 3.9 months in non-functional lung and gastrointestinal tumours, and cabozantinib was approved in 2025 after the extra-pancreatic cohort of CABINET (New England Journal of Medicine 2024) showed 8.4 against 3.9 months.\n\nSurgery keeps its place even in metastatic disease: resection of the primary with its mesenteric nodes prevents obstruction and ischaemia, and liver metastases are debulked, ablated or embolised when the liver dominates. Carcinoid syndrome is treated by raising the somatostatin analogue dose, adding telotristat ethyl for diarrhoea that persists (TELESTAR, 2017), and giving octreotide by infusion around operations and embolisation to prevent carcinoid crisis. The order of radioligand therapy, everolimus and cabozantinib after somatostatin analogues has never been randomised; COMPETE (Lancet 2025) showed 177Lu-edotreotide beat everolimus on progression-free survival in grade 1 to 2 gastroenteropancreatic tumours, alpha-emitting radioligands are in phase 3 after lutetium failure, and the oral somatostatin agonist paltusotine and a subcutaneous octreotide depot are being tested for carcinoid syndrome.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"PROMID (JCO 2009)","url":"https://doi.org/10.1200/JCO.2009.22.8510"},{"label":"NETTER-1 (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1607427"},{"label":"NETTER-2 (Lancet 2024)","url":"https://doi.org/10.1016/S0140-6736(24)00701-3"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":["subtype-page","endocrine"],"related":["grade-3-net","lung-net","pancreatic-net","lu-177"],"indications":[],"sections":[],"technologies":["sstr-pet","prrt","radioligand-therapy","radioembolisation-tare"],"targets":["sstr2"],"drugs":["lutathera","everolimus","cabozantinib","ga68-dotatate","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["net-grade-ki67","prrt-term"],"trials":["netter-1","nct03972488","radiant-3-4","cabinet","compete"],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-2-lancet-2024","paper-clarinet-lanreotide-nejm-2014","paper-netter-1-nejm-2017"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"The commonest neuroendocrine tumour of the gut in Western series and now the commonest cancer of the small intestine; most are grade 1 or 2 and many are found only after they have reached the mesenteric nodes or the liver.","subtypes":["Ileal neuroendocrine tumour (the classic site, often multifocal)","Jejunal neuroendocrine tumour","Duodenal neuroendocrine tumour (gastrinoma, somatostatinoma, ampullary)","Small bowel NET with carcinoid syndrome and liver metastases","Small bowel NET with mesenteric fibrosis and obstruction","Grade 1 (Ki-67 under 3 percent) and grade 2 (3 to 20 percent) small intestinal NET"],"biomarkers":["Ki-67 index and mitotic count (WHO grade, nearly always grade 1 or 2)","Chromogranin A (monitoring, raised by proton-pump inhibitors and kidney disease)","24-hour urinary 5-HIAA (carcinoid syndrome)","Somatostatin receptor PET with gallium-68 or copper-64 DOTATATE (staging and radioligand eligibility)","Echocardiography for carcinoid heart disease","Germline CDKN1B in familial small intestinal NET (rare)"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Biopsy with Ki-67 grading, somatostatin receptor PET, cross-sectional imaging of the liver, chromogranin A and urinary 5-HIAA, echocardiography if carcinoid syndrome is present.","refs":["sstr-pet","ga68-dotatate","net-grade-ki67"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Localised or resectable disease","approach":"Segmental small bowel resection with mesenteric lymphadenectomy, inspecting the whole small bowel for further primaries; the primary is often removed even when liver metastases are present.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Advanced, first line","approach":"Octreotide LAR or lanreotide (PROMID, CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2).","refs":["lutathera","nct03972488","prrt"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Progression on a somatostatin analogue","approach":"Lutetium-177 dotatate (NETTER-1); everolimus (RADIANT-4); cabozantinib (CABINET); liver-directed therapy for hepatic-dominant disease.","refs":["lutathera","netter-1","everolimus","radiant-3-4","cabozantinib","cabinet","radioembolisation-tare"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Carcinoid syndrome","approach":"Somatostatin analogue dose escalation, telotristat ethyl for refractory diarrhoea, octreotide infusion around procedures to prevent carcinoid crisis, valve surgery for carcinoid heart disease.","refs":[],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"After radioligand therapy","approach":"Everolimus or cabozantinib; 177Lu-edotreotide if approved; alpha-emitting radioligands and retreatment in trials.","refs":["everolimus","cabozantinib","itm-11","compete","ryz101","action-1","alphamedix"],"guideline":{"version":"NCCN Guidelines: Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}}],"stateOfArt":["NETTER-1 made this the first cancer treated by a modern radioligand and NETTER-2 has moved that treatment to first line for the faster-growing tumours.","Somatostatin analogues remain the first drug for almost every patient, controlling both hormone symptoms and growth.","Cabozantinib gives a fourth approved systemic option, and COMPETE was the first head-to-head win for a radioligand over a targeted tablet."],"history":[{"year":1907,"title":"Oberndorfer names the small bowel tumours 'Karzinoid'","refs":[]},{"year":1954,"title":"Carcinoid syndrome described","refs":[]},{"year":1988,"title":"Octreotide approved for carcinoid syndrome symptoms","refs":[]},{"year":2009,"title":"PROMID: octreotide LAR slows midgut tumour growth","refs":[]},{"year":2014,"title":"CLARINET: lanreotide halves the risk of progression in enteropancreatic tumours","refs":[]},{"year":2016,"title":"RADIANT-4 extends everolimus to gut and lung tumours; gallium-68 DOTATATE PET approved","refs":["radiant-3-4","everolimus","sstr-pet","ga68-dotatate"]},{"year":2017,"title":"NETTER-1 published; telotristat ethyl approved for carcinoid syndrome diarrhoea","refs":["netter-1"]},{"year":2018,"title":"Lutathera approved in the United States and Europe","refs":["lutathera","prrt"]},{"year":2024,"title":"NETTER-2: lutetium-177 dotatate first line for grade 2 to 3 tumours; CABINET published","refs":["nct03972488","lutathera","cabinet"]},{"year":2025,"title":"Cabozantinib approved for previously treated neuroendocrine tumours; COMPETE published","refs":["cabozantinib","compete"]}],"pipeline":["itm-11","compete","ryz101","action-1","alphamedix","idea-net-antagonist-ligands","idea-net-dosimetry-prrt"],"openProblems":["No randomised trial orders radioligand therapy, everolimus and cabozantinib after somatostatin analogues.","Whether removing the primary improves survival in patients with liver metastases has never been tested prospectively.","Chromogranin A is unreliable and no blood test yet replaces imaging for follow-up.","Overall survival gains are hard to show because patients live for years and cross over."],"parent":"neuroendocrine","route":"/indications/small-intestinal-net/"}
{"id":"thyroid","kind":"indication","name":"Thyroid cancer","aka":[],"tldr":"Thyroid cancer is usually curable with surgery and radioactive iodine, the original theranostic. Rare aggressive forms respond to RET and BRAF inhibitors.","summary":"Thyroid cancer is really several diseases. Differentiated thyroid cancer (papillary ~85%, follicular, oncocytic) arises from follicular cells, retains iodine uptake, and has a 10-year survival above 95%; its incidence has tripled in many countries because ultrasound finds tiny tumours that would never have caused harm. Medullary thyroid cancer comes from calcitonin-producing C cells, is driven by RET mutations (hereditary in MEN2), and does not take up iodine. Anaplastic thyroid cancer is rare, dedifferentiated, and historically progressed within months; BRAF/MEK inhibition and immunotherapy have started to change that.\n\nDifferentiated disease is treated by surgery, with radioactive iodine (the first theranostic, 1946) reserved for intermediate and high-risk patients after HiLo, ESTIMABL2, and IoN showed low-risk patients gain nothing from it; active surveillance is accepted for microcarcinomas, and lobectomy suffices for many. When cancer becomes radioiodine-refractory, lenvatinib (SELECT) and sorafenib (DECISION) extend progression-free survival, and genotype directs selective therapy: selpercatinib for RET fusions, larotrectinib for NTRK, dabrafenib-trametinib for BRAF. Medullary cancer moved from vandetanib and cabozantinib to RET-selective selpercatinib after LIBRETTO-531 (2023). Anaplastic cancer with BRAF V600E responds to dabrafenib-trametinib (ROAR), often enabling surgery, and triplets with pembrolizumab are producing multi-year survivors.\n\nThe field's biggest problems are the opposite of most cancers': over-detection and over-treatment of indolent disease, alongside the unsolved lethality of anaplastic and RAI-refractory disease, resistance to RET inhibitors (solvent-front mutations), and the toxicity of long-term multikinase therapy.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Thyroid_cancer"}],"tags":["endocrine","spike"],"related":["radiopharma-roadmap","theranostics"],"indications":[],"sections":[],"technologies":["radioligand-therapy","radioiodine-therapy"],"targets":[],"drugs":["radioactive-iodine","thyrotropin-alfa"],"companies":["eli-lilly","bayer","novartis","astrazeneca"],"institutions":["md-anderson","mskcc"],"pathways":[],"terms":["theranostics"],"trials":["nct06860971","nct03690388","select-lenvatinib","decision-sorafenib","estimabl2","ion-trial","hilo","astra"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"~820,000 cases per year; most are indolent papillary cancers with >98% survival.","subtypes":["Papillary (~85%; BRAF V600E ~50%, RET/PTC fusions, RAS)","Follicular (RAS, PAX8-PPARG)","Oncocytic (Hürthle cell)","Poorly differentiated","Anaplastic (BRAF V600E ~40%, TP53, TERT)","Medullary (RET germline in MEN2 ~25%; somatic RET M918T)","Papillary microcarcinoma (≤1 cm; surveillance candidate)","Paediatric differentiated thyroid cancer (fusion-driven, often nodal, excellent survival)"],"biomarkers":["BRAF V600E","RET fusion/mutation","NTRK","RAS","TERT","Thyroglobulin and anti-Tg antibodies (surveillance of differentiated cancer)","Calcitonin and CEA (medullary)","Germline RET (MEN2 screening, prophylactic thyroidectomy)","Somatic RET fusion/mutation (selpercatinib)","BRAF V600E (prognosis; anaplastic targeted therapy; redifferentiation)","TERT promoter (aggressiveness)","NTRK, ALK fusions (tumour-agnostic drugs)","Bethesda cytology category and molecular classifier result","Radioiodine avidity on diagnostic scan"],"standardOfCare":[{"setting":"Differentiated","approach":"Thyroidectomy ± radioactive iodine; TSH suppression.","refs":["radioligand-therapy"],"guideline":{"version":"NCCN Guidelines: Thyroid Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470"}},{"setting":"Advanced/refractory","approach":"Lenvatinib; selpercatinib (RET); BRAF/MEK (anaplastic).","refs":[],"guideline":{"version":"NCCN Guidelines: Thyroid Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470"}},{"setting":"Nodule work-up","approach":"Ultrasound with TI-RADS; FNA only for nodules meeting size/appearance thresholds; Bethesda reporting; molecular classifier (Afirma, ThyroSeq) for indeterminate results.","refs":[],"guideline":{"nccn":"2A","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470"}},{"setting":"Papillary microcarcinoma (≤1 cm, no spread)","approach":"Active surveillance or lobectomy; total thyroidectomy and radioiodine not indicated.","refs":[],"guideline":{"nccn":"2A"}},{"setting":"Low-risk differentiated (pT1-T2 N0)","approach":"Lobectomy or total thyroidectomy; no radioiodine ablation (ESTIMABL2, IoN); modest TSH suppression then normal-range TSH.","refs":["estimabl2","ion-trial"],"guideline":{"nccn":"2A"}},{"setting":"Intermediate/high-risk differentiated","approach":"Total thyroidectomy with therapeutic node dissection; radioiodine (1.1-3.7 GBq adjuvant; higher for known metastases) after recombinant TSH; TSH suppression.","refs":["radioactive-iodine","radioiodine-therapy","hilo"],"guideline":{"nccn":"2A"}},{"setting":"Radioiodine-refractory, progressive","approach":"Genotype first: selpercatinib (RET fusion), larotrectinib/entrectinib (NTRK), dabrafenib-trametinib (BRAF V600E); otherwise lenvatinib (or sorafenib); consider MAPK-inhibitor redifferentiation to restore iodine uptake.","refs":["select-lenvatinib","decision-sorafenib"],"guideline":{"nccn":"1 (lenvatinib)","esmoMcbs":"3"}},{"setting":"Medullary, localised","approach":"Total thyroidectomy with central neck dissection; prophylactic thyroidectomy in RET germline carriers by codon-based age; calcitonin surveillance.","refs":[],"guideline":{"nccn":"2A"}},{"setting":"Medullary, advanced progressive RET-mutant","approach":"Selpercatinib first line (LIBRETTO-531); cabozantinib or vandetanib if RET-selective therapy unavailable or failed.","refs":[],"guideline":{"nccn":"1 (preferred)","esmoMcbs":"3"}},{"setting":"Anaplastic, BRAF V600E","approach":"Rapid BRAF testing; dabrafenib-trametinib (ROAR), often with pembrolizumab, then surgery and radiation if rendered resectable.","refs":[],"guideline":{"nccn":"2A"}},{"setting":"Anaplastic, BRAF wild-type","approach":"Multimodal chemoradiation (paclitaxel-based) if feasible; lenvatinib; immunotherapy for PD-L1-high or TMB-high; NTRK/RET/ALK agents if fusion-positive; early palliative care.","refs":["pembrolizumab"]},{"setting":"Survivorship","approach":"Lifelong levothyroxine with risk-adapted TSH targets; calcium/PTH monitoring after surgery; salivary care after radioiodine; low-risk patients can be discharged to primary care.","refs":[]}],"stateOfArt":["Genotype-directed therapy for aggressive subtypes.","De-escalation is the story: radioiodine omitted for low-risk disease (ESTIMABL2, IoN), low-dose ablation when needed (HiLo), lobectomy and active surveillance for small tumours.","Genotype-directed therapy covers most aggressive disease: RET (selpercatinib beat multikinase inhibitors head to head), BRAF, NTRK, ALK.","Anaplastic thyroid cancer with BRAF V600E has moved from a median survival under six months to 15 months with the doublet and longer with immunotherapy added, and neoadjuvant use enables surgery.","Molecular classifiers on needle biopsies have halved diagnostic surgery for indeterminate nodules.","Redifferentiation with MAPK inhibitors can restore radioiodine uptake in about half of refractory patients."],"history":[{"year":1946,"title":"Radioactive iodine: first theranostic","refs":[]},{"year":1946,"title":"First patient treated with radioactive iodine for metastatic thyroid cancer","note":"Seidlin, Marinelli, and Oshry: the first theranostic.","refs":["radioactive-iodine","radioiodine-therapy"]},{"year":1985,"title":"RET proto-oncogene identified; MEN2 germline RET mutations follow (1993)","refs":[]},{"year":2003,"title":"BRAF V600E found in ~45% of papillary thyroid cancers","refs":[]},{"year":2009,"title":"Bethesda System for thyroid cytology standardises nodule reporting","refs":[]},{"year":2011,"title":"Vandetanib: first drug for medullary thyroid cancer","refs":[]},{"year":2012,"title":"HiLo and ESTIMABL1: low-dose radioiodine ablation is enough","refs":["hilo"]},{"year":2013,"title":"Sorafenib approved for RAI-refractory disease (DECISION); selumetinib redifferentiation proof of concept","refs":["decision-sorafenib"]},{"year":2015,"title":"Lenvatinib approved (SELECT); ATA guidelines endorse active surveillance and less radioiodine","refs":["select-lenvatinib"]},{"year":2018,"title":"Dabrafenib-trametinib approved for BRAF V600E anaplastic thyroid cancer (ROAR); larotrectinib tumour-agnostic","refs":[]},{"year":2020,"title":"Selpercatinib approved","refs":[]},{"year":2020,"title":"Selpercatinib and pralsetinib: RET-selective inhibitors approved","refs":[]},{"year":2022,"title":"ESTIMABL2: no radioiodine for low-risk disease; ASTRA adjuvant redifferentiation negative","refs":["estimabl2","astra"]},{"year":2023,"title":"LIBRETTO-531: selpercatinib beats cabozantinib/vandetanib in medullary cancer","refs":[]},{"year":2025,"title":"IoN confirms omission of radioiodine in low-risk disease (Lancet)","refs":["ion-trial"]},{"year":2026,"title":"Selpercatinib label update (July 2026)","refs":[]}],"pipeline":["al2846","pembrolizumab","targeted-alpha-therapy"],"openProblems":["Overdiagnosis of microcarcinoma.","Anaplastic thyroid cancer: BRAF V600E cases now respond to dabrafenib-trametinib, often enough to allow surgery; the 60% without the mutation still have few options.","Overdiagnosis: incidence has tripled with no change in mortality; most detected cancers would never have caused harm, yet surveillance uptake outside Japan and Korea remains low.","Anaplastic thyroid cancer without BRAF V600E (about 60%) still has a median survival of a few months.","Resistance to RET-selective inhibitors via solvent-front (G810) mutations has no approved next-generation drug.","Multikinase inhibitors for RAI-refractory disease cause hypertension, weight loss, and fatigue; most patients need dose reductions and quality of life suffers.","No validated way to predict which low-risk patients will be the rare ones to recur, so follow-up intensity is uniform.","Redifferentiation works in about half of refractory patients but predictors and optimal regimens are undefined.","Paediatric and radiation-induced thyroid cancers (Chernobyl, Fukushima cohorts) have distinct fusion-driven biology that is under-studied.","Hereditary MEN2 requires lifelong surveillance and prophylactic surgery in children; long-term outcomes of RET-selective therapy in this group are unknown."],"route":"/indications/thyroid/"}
{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","aka":[],"tldr":"Actinium-225 is the alpha-emitting atom behind the most promising next wave of radioligand therapies, and there is not enough of it. Almost all of it used to come from one decaying stock of thorium in a US national laboratory. New routes use accelerators and old radium.","summary":"Actinium-225 (half-life 9.9 days) delivers four alpha particles per decay chain, which is why it is being tested attached to PSMA ligands, somatostatin analogues and other carriers in Phase 3 programmes by Novartis, Bristol Myers Squibb (through RayzeBio), Bayer, AstraZeneca and others. Historically the world's supply came from thorium-229 that itself decays from uranium-233 held by the US Department of Energy, milked from generators at Oak Ridge National Laboratory and by the Institute for Transuranium Elements in Karlsruhe, and amounted to enough for only a few thousand patient doses a year. That is the binding constraint on targeted alpha therapy.\n\nFour routes are being built. First, more thorium-229: TerraPower Isotopes is extracting it from DOE uranium-233 as the material is downblended, and is building a production plant in Philadelphia. Second, high-energy proton spallation of thorium-232 at the DOE Tri-Lab effort (Brookhaven, Los Alamos and Oak Ridge), which yields large quantities contaminated with a small fraction of long-lived actinium-227 that complicates waste and regulatory acceptance. Third, radium-226 targets irradiated on medium-energy cyclotrons (the (p,2n) reaction), pursued by Eckert & Ziegler, Nusano, Ionetix and others, and photonuclear irradiation of radium with electron accelerators (NorthStar, Niowave), both of which depend on recovering and handling legacy radium sources. Fourth, in-house production by the sponsors themselves, as RayzeBio and Bayer have set up. The US DOE Isotope Program, the IAEA and industry groups track the totals; the pharmacopoeial question of how much actinium-227 is acceptable in a drug is unsettled and affects which routes can supply approved products. Lead-212, made from thorium-228 generators by Orano Med, is the main alpha-emitting alternative with its own supply chain.","status":"phase-3","asOf":"2026-09-17","links":[{"label":"US DOE Isotope Program","url":"https://www.isotopes.gov/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Actinium-225"}],"tags":["manufacturing-wave"],"related":["ac-225","pb-212"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["therapy-isotope-supply-chain","targeted-alpha-therapy","cyclotron-isotope-production","research-reactor-isotope-production","radiopharmaceutical-gmp-release","alpha-nanogenerators"],"targets":[],"drugs":["ryz101","ac225-psma","fpi-2265","alphamedix"],"companies":["terrapower-isotopes","eckert-ziegler","northstar-medical-radioisotopes","nusano","rayzebio","bms","bayer","novartis","astrazeneca","orano-med","itm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide manufacturing expansion","editedOn":"2026-09-17"},"principle":"Alpha-emitter supply from thorium-229 generators, accelerator spallation of thorium-232 or irradiation of radium-226, each with a different impurity and waste profile.","strengths":["Several independent routes under construction","Sponsors are integrating supply in-house","Lead-212 offers an alternative alpha chain"],"limitations":["Supply is a fraction of Phase 3 demand","Actinium-227 impurity from spallation","Radium-226 targets are scarce and hazardous"],"since":2013,"route":"/technologies/actinium-225-supply/"}
{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","aka":[],"tldr":"Actinium-225 releases four alpha particles as it decays, but the daughters escape and irradiate the kidneys and salivary glands. Nanocarriers try to hold them in place.","summary":"The therapeutic power of actinium-225 comes from its decay chain, but recoil energy ejects daughter nuclides from any chelator, causing off-target dose. Nanoparticle carriers (lanthanum phosphate, titanium dioxide, liposomes) and polymer cages are designed to retain daughters long enough for them to decay inside the tumour. Retention above 90% has been reported in animals; no such construct had reached human trials by 2026.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: actinium-225","url":"https://clinicaltrials.gov/search?term=actinium-225"}],"tags":["frontier","radical"],"related":["ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":["perspective-therapeutics","aktis-oncology","terrapower-isotopes"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Encapsulating the parent nuclide in a solid-state or multi-shell carrier physically retains recoiling daughters, converting a leaky decay chain into a contained one.","strengths":["Could remove the main toxicity limit on actinium therapy","Multiplies alpha dose per targeting event","Compatible with existing targeting ligands"],"limitations":["No human data","Nanoparticle biodistribution favours liver and spleen","No trodden regulatory path for a radioactive nanomaterial"],"route":"/technologies/alpha-nanogenerators/"}
{"id":"astatine-211-alpha-therapy","kind":"technology","name":"Astatine-211 alpha therapy","aka":[],"tldr":"A rare alpha-emitting halogen that can be attached to antibodies and small molecules like iodine, tested in leukaemia conditioning and brain and ovarian cancer.","summary":"Astatine-211 is an alpha emitter with a 7.2-hour half-life that behaves chemically like iodine, so it can label antibodies and small molecules by radiohalogenation. Its short range and high energy suit micrometastatic and disseminated disease; academic programmes in Gothenburg, Seattle and Japan have tested At-211 antibodies in ovarian cancer and as anti-CD45 conditioning before transplant, and At-211 PSMA and MABG agents are in early trials. Production requires a cyclotron with alpha beams, limiting supply to a few centres.","status":"phase-1","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Astatine","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Astatine"}],"tags":[],"related":["at-211"],"indications":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["targeted-alpha-therapy","medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"At-211 is produced by bombarding bismuth with alpha particles, labelled to a targeting molecule, and delivers high linear-energy-transfer alpha particles over a few cell diameters.","strengths":["Alpha emission kills with few decays and overcomes resistance","Iodine-like chemistry fits existing tracers","Short half-life limits residual dose"],"limitations":["Very limited production capacity","Short half-life constrains logistics","Early clinical stage"],"route":"/technologies/astatine-211-alpha-therapy/"}
{"id":"auger-electron-therapy","kind":"technology","name":"Auger-electron therapy","aka":[],"tldr":"Auger-electron therapy uses radioactive atoms such as iodine-125 or terbium-161 that release cascades of low-energy electrons travelling only nanometres to micrometres, so they kill a cell only if the atom sits on or inside its DNA and spare the neighbours. Terbium-161 can replace lutetium-177 in existing PSMA ligands; true nuclear delivery remains preclinical.","summary":"Auger emitters such as iodine-125, indium-111 and terbium-161 release cascades of low-energy electrons with nanometre to micrometre range. Delivered into the nucleus they are exquisitely cytotoxic and, unlike alpha emitters, spare neighbouring cells almost entirely. Terbium-161 is closest to clinical use because it can be substituted for lutetium-177 in existing PSMA and somatostatin ligands, with first-in-human work reported; strategies that require true nuclear delivery remain preclinical.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: terbium-161","url":"https://clinicaltrials.gov/search?term=terbium-161"}],"tags":["frontier","radical"],"related":["in-111","lu-177","tb-161"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","radioimmunotherapy"],"targets":["psma","sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Electron-capture or internal-conversion decay releases multiple very low-energy electrons; energy deposition is confined to a few nanometres, so proximity to DNA determines lethality.","strengths":["Single-cell selectivity, well suited to micrometastases","Minimal crossfire into normal tissue","Terbium-161 slots into existing ligand chemistry"],"limitations":["Needs delivery into the nucleus for the pure Auger effect","Isotope supply and short half-lives","Dosimetry models built for beta emitters do not apply"],"route":"/technologies/auger-electron-therapy/"}
{"id":"caix-pet","kind":"technology","name":"CAIX PET (89Zr-girentuximab)","aka":[],"tldr":"CAIX PET is a scan using an antibody against a protein almost unique to clear-cell kidney cancer, to tell cancer from benign kidney lumps without a biopsy.","summary":"CAIX PET uses 89Zr-labelled girentuximab, an antibody against carbonic anhydrase IX, a HIF target expressed in more than 95% of clear-cell renal cell carcinomas because of VHL loss. Imaging 5 days after injection shows whether an indeterminate renal mass is clear-cell cancer without a biopsy. In the ZIRCON phase 3 (2023) it achieved sensitivity 86% and specificity 87%, giving histology-level specificity and whole-body staging in one scan. Telix's TLX250-CDx received an FDA complete response letter in 2025 over manufacturing, and resubmission is planned, so it is not yet approved; the five-day imaging delay and the 89Zr dose are practical limitations. The same antibody labelled with 177Lu is being tested therapeutically in the STARLITE trials, making CAIX a theranostic pair. It tells cancer from a benign kidney lump by lighting up a protein almost unique to clear-cell kidney cancer.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"Shuch et al., ZIRCON: 89Zr-girentuximab PET-CT imaging of clear-cell renal cell carcinoma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(24)00402-9"}],"tags":[],"related":["zr-89","lu-177"],"indications":["rcc"],"sections":[],"technologies":["immuno-pet","pet"],"targets":[],"drugs":[],"companies":["telix"],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"89Zr-labelled anti-CAIX antibody girentuximab imaged 5 days after injection; CAIX is a HIF target expressed in >95% of clear-cell RCC via VHL loss.","strengths":["Non-invasive histology-level specificity","Whole-body staging of clear-cell disease"],"limitations":["Five-day imaging delay; 89Zr dose","Not yet approved (CRL 2025)"],"route":"/technologies/caix-pet/"}
{"id":"ct","kind":"technology","name":"CT (computed tomography)","aka":[],"tldr":"A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread.","summary":"Computed tomography rotates an X-ray source and detector around the body and reconstructs the measured attenuation into cross-sectional images, with iodinated contrast highlighting vasculature. In use since 1971, it is the workhorse of staging and response assessment and the standard measurement tool for RECIST. It is fast, ubiquitous, offers sub-millimetre resolution and is excellent for lung, liver, bone and lymph nodes. Its limits are that it shows anatomy only, so it cannot distinguish scar from live tumour or give biological information, it has limited soft-tissue contrast, it performs poorly for brain, marrow and small peritoneal disease, and it delivers ionising radiation. Photon-counting CT improves resolution at lower dose, while PET/CT and MRI fill the gaps in biology and soft tissue. CT is the quick 3D X-ray that most cancer decisions are measured against.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CT_scan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CT_scan"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","canon-medical","united-imaging"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A rotating X-ray source and detector measure attenuation, which is reconstructed into cross-sectional images. Iodinated contrast highlights vasculature.","strengths":["Fast, ubiquitous","Sub-millimetre resolution","Standard for RECIST response"],"limitations":["Anatomic only; cannot distinguish scar from live tumour","Radiation dose","Poor for brain, marrow, and small peritoneal disease"],"since":1971,"route":"/technologies/ct/"}
{"id":"cyclotron-isotope-production","kind":"technology","name":"Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)","aka":[],"tldr":"Proton-rich isotopes for PET scans and some therapies are made by hitting a target with a beam from a cyclotron. Fluorine-18 is made every morning within driving distance of the scanner; gallium-68 comes from either a generator or a cyclotron; copper-64 and zirconium-89 last long enough to ship across a country.","summary":"A medical cyclotron accelerates protons (or for a few isotopes deuterons or alpha particles) into a target whose nuclei absorb them and emit neutrons. Fluorine-18 (half-life 110 minutes) is made from oxygen-18-enriched water in almost every PET-producing radiopharmacy and cyclotron centre, then built into FDG, PSMA and other tracers by automated synthesis modules; distribution is limited to a few hours' travel. Gallium-68 (68 minutes) has two routes: a germanium-68/gallium-68 generator that a hospital elutes several times a day for about a year (made by Eckert & Ziegler, IRE ELiT and ITM among others), or direct cyclotron production from zinc-68 targets, which regulators have accepted for PSMA kits in the United States and which frees users from generator allocation. Copper-64 (12.7 hours, from nickel-64) and zirconium-89 (78 hours, from yttrium-89) allow central manufacture and national shipping, so copper-64 dotatate is made at a few sites and flown to scanners across the United States. Astatine-211 for alpha therapy needs an alpha beam of about 28 MeV on bismuth, which only a handful of cyclotrons in the world can deliver, and actinium-225 can be made from radium-226 targets on medium-energy cyclotrons (covered in the actinium record).\n\nThe machines and the shielded hot cells and synthesis modules are covered in the existing cyclotron record; this record is about the isotopes and their supply. Capacity constraints are target material (enriched oxygen-18 water, zinc-68, nickel-64 and above all radium-226), beam time shared between commercial tracers, and the GMP burden on hospital sites under 21 CFR 212 and EU Annex 3. The cyclotron makers are IBA, GE HealthCare, Siemens Healthineers (through PETNET) and Sumitomo, and the commercial networks (PETNET, Cardinal Health, SOFIE, Curium, Jubilant) run most of the daily production.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"},{"label":"IAEA: cyclotron produced radionuclides","url":"https://www.iaea.org/publications/7892/cyclotron-produced-radionuclides-principles-and-practice"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fluorine-18"}],"tags":["manufacturing-wave"],"related":["f-18","ga-68","cu-64","zr-89","ge-68","ac-225","at-211"],"indications":[],"sections":[],"technologies":["medical-cyclotrons-synthesis-modules","pet-tracer-manufacturing","radionuclide-generators-kits","radiopharmacy-network","research-reactor-isotope-production","actinium-225-supply","pet","psma-pet","astatine-211-alpha-therapy"],"targets":[],"drugs":["ga68-dotatate"],"companies":["iba","ge-healthcare","siemens-healthineers","petnet-solutions","cardinal-health","sofie-biosciences","curium","jubilant-radiopharma","eckert-ziegler","ire","telix","lantheus","radiomedix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide manufacturing expansion","editedOn":"2026-09-17"},"principle":"Charged-particle nuclear reactions on enriched targets produce short-lived positron emitters and some alpha emitters, distributed within hours or, for longer-lived isotopes, days.","strengths":["Distributed production near scanners","No reactor or fissile material","Cyclotron gallium relieves generator limits"],"limitations":["Enriched target materials","Beam time and same-day logistics","Only a few machines can make astatine-211"],"since":1976,"route":"/technologies/cyclotron-isotope-production/"}
{"id":"fapi-pet","kind":"technology","name":"FAPI PET","aka":[],"tldr":"FAPI PET is a PET scan that lights up the scaffolding around almost any solid tumour, including cancers the standard sugar scan misses.","summary":"Quinoline-based FAP inhibitors (FAPI-04, FAPI-46, FAPI-74) labelled with 68Ga or 18F image cancer-associated fibroblasts. Superior to FDG in pancreatic, gastric, HCC, and peritoneal disease in head-to-head series. Registrational trials for 68Ga-FAPI-46 and 18F-FAPI-74 (Sofie) are underway. Pairs with FAP-targeted radioligands.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha"}],"tags":[],"related":["f-18","ga-68"],"indications":["hcc"],"sections":[],"technologies":["pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecule binds FAP on stromal fibroblasts; rapid uptake, low background, minimal brain and liver signal.","strengths":["Pan-cancer, high contrast","No fasting needed","Sees desmoplastic tumours FDG misses"],"limitations":["Also uptake in fibrosis, healing, arthritis","Reports stroma not tumour cells","Not yet approved"],"since":2018,"route":"/technologies/fapi-pet/"}
{"id":"fdg-pet","kind":"technology","name":"FDG PET","aka":[],"tldr":"FDG PET is the standard PET scan. A radioactive sugar shows which tissues are burning glucose fast, which most cancers do.","summary":"FDG PET uses 18F-fluorodeoxyglucose, a radioactive sugar analogue taken up through GLUT transporters and trapped after phosphorylation by hexokinase, exploiting the Warburg effect by which most cancers burn glucose fast. It is the standard PET scan for staging and response in lymphoma (scored on the Deauville scale), lung cancer, melanoma, head and neck cancer and oesophageal cancer, with universal availability and decades of validation. Its limits are biological: infection and inflammation are also hot, normal brain uptake creates a high background, and indolent tumours are poorly seen. It is weak in prostate cancer, low-grade neuroendocrine tumours, mucinous cancers and some breast cancers, which is why target-specific tracers such as PSMA and SSTR ligands exist. FDG PET shows which tissues are consuming glucose fastest, and most, though not all, cancers do.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)"}],"tags":[],"related":["f-18"],"indications":["nsclc"],"sections":[],"technologies":["pet"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":["suv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct"],"notes":[],"principle":"FDG is taken up via GLUT transporters and trapped after phosphorylation by hexokinase.","strengths":["Universal availability","Decades of validation"],"limitations":["Non-specific: infection and inflammation are also hot","Brain background","Poor in indolent tumours"],"route":"/technologies/fdg-pet/"}
{"id":"fes-pet","kind":"technology","name":"FES PET (oestrogen receptor imaging)","aka":["18F-fluoroestradiol PET","Cerianna","oestrogen receptor PET","ER PET"],"tldr":"A PET scan using a radioactive form of oestrogen that lights up every tumour deposit still carrying the oestrogen receptor, so doctors can see whether metastases across the body will respond to hormone treatment without biopsying each one.","summary":"What it measures. 18F-fluoroestradiol is oestradiol carrying a positron-emitting fluorine atom. Injected into a vein, it binds oestrogen receptors wherever they are expressed, and a PET scan maps that binding. A tumour that lights up is receptor positive; one that is dark either never had the receptor or has lost it, which happens in a quarter or more of metastases from an originally receptor-positive breast cancer.\n\nWho should have it. The FDA approved 18F-fluoroestradiol (Cerianna, developed by Zionexa and now sold by GE HealthCare) in May 2020 as an adjunct to biopsy in patients with recurrent or metastatic breast cancer, to detect oestrogen receptor positive lesions. The Society of Nuclear Medicine and Molecular Imaging's appropriate use criteria list it as appropriate when biopsy is not feasible or lesions are discordant, when deciding whether to continue endocrine therapy after progression, and in lobular and other cancers that FDG PET images poorly. It is not a screening or staging test and it is uninformative in a patient taking a drug that blocks the receptor, such as fulvestrant, unless that drug has been paused.\n\nWhat changes. A uniformly bright scan supports endocrine therapy or a hormone-based combination; dark lesions steer towards chemotherapy or an antibody-drug conjugate for those sites, and a mixed picture explains why a patient is progressing at one site on a treatment that works elsewhere. The tracer is made in regional cyclotron facilities and shipped, so availability follows the PET tracer network; the scan is priced like other specialist PET studies and is covered in the United States for the approved indication. In Europe it is available at a small number of centres under national rules.","status":"approved","asOf":"2026-09-17","links":[{"label":"Wikipedia: Fluoroestradiol F-18","url":"https://en.wikipedia.org/wiki/Fluoroestradiol_F-18"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet","pet-ct","fdg-pet","her2-pet","psma-pet","fapi-pet","pet-tracer-manufacturing","quantitative-imaging-biomarkers"],"targets":[],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"16-alpha-18F-fluoro-17-beta-oestradiol binds oestrogen receptor alpha with high affinity; PET quantifies uptake in each lesion, and standardised uptake thresholds separate receptor-positive from receptor-negative deposits.","strengths":["Whole-body map of receptor status without multiple biopsies","Shows heterogeneity between metastases","FDA approved with published appropriate use criteria"],"limitations":["Uninformative while a receptor-blocking drug is on board","Liver uptake obscures liver metastases","Limited tracer availability outside large centres"],"since":2020,"route":"/technologies/fes-pet/"}
{"id":"gamma-probes-dose-calibrators","kind":"technology","name":"Gamma probes, handheld gamma cameras and dose calibrators","aka":[],"tldr":"The small radiation detectors that make nuclear medicine and sentinel node surgery work: a pen-sized probe that clicks when the surgeon nears the radioactive lymph node, and the well counter in the hot lab that checks every dose before it is injected.","summary":"Sentinel lymph node biopsy replaced full node clearance in breast cancer and melanoma because the surgeon can find the node with a handheld gamma probe: a collimated scintillation or semiconductor detector that counts the technetium-99m nanocolloid injected around the tumour, guiding the incision and confirming when the hot nodes are out. Devicor's Neoprobe (now under Mammotome), Eurorad's Europrobe, Crystal Photonics' CrystalProbe and drop-in probes for robotic surgery from Lightpoint Medical are the main devices; small handheld gamma cameras such as Sentinella and Crystal Cam image the node field, and PET-emitting tracers such as gallium-68 PSMA are detected with high-energy probes in radioguided prostate surgery. Magnetic tracers detected by Endomag's Sentimag (also now part of Mammotome) offer the same localisation without radioactivity. In the radiopharmacy and hot lab, dose calibrators, ionisation well chambers such as Capintec's CRC series (Mirion) and Comecer's, measure the activity of every syringe of diagnostic tracer or therapeutic radioligand against the prescription, and survey meters and contamination monitors protect staff.\n\nThe probe technique needs a nuclear medicine department to inject and image the tracer, a supply of technetium-99m from molybdenum generators, and radiation-protection handling of specimens; magnetic and fluorescent alternatives remove the isotope but have their own artefacts. Dose calibrators are inexpensive but require regular constancy, linearity and geometry checks and isotope-specific calibration factors, especially for the new alpha and beta therapy isotopes.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"Wikipedia: sentinel lymph node","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"},{"label":"Mammotome: Neoprobe gamma detection system","url":"https://www.mammotome.com/"},{"label":"IAEA: quality assurance for radioactivity measurement in nuclear medicine (Technical Reports Series 454)","url":"https://www.iaea.org/publications/7451/quality-assurance-for-radioactivity-measurement-in-nuclear-medicine"}],"tags":["machines-wave2"],"related":["medical-cyclotrons-synthesis-modules","radioligand-dosimetry","ga-68","tc-99m"],"indications":["prostate"],"sections":[],"technologies":["spect-ct","radioligand-therapy","psma-pet","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["comecer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Collimated scintillation or cadmium zinc telluride detectors count gamma photons from a tracer in the sentinel node to guide surgical localisation; pressurised ionisation well chambers measure the activity of radiopharmaceutical doses by ionisation current with isotope-specific calibration factors.","strengths":["Enables sentinel node surgery and radioguided resection","Every dose measured before injection","Cheap and widely available"],"limitations":["Depends on isotope supply and a nuclear medicine department","Radiation protection of theatre and pathology staff","Calibration factors needed for new therapy isotopes"],"since":1990,"route":"/technologies/gamma-probes-dose-calibrators/"}
{"id":"her2-pet","kind":"technology","name":"HER2 PET","aka":[],"tldr":"HER2 PET is a PET scan using radiolabelled trastuzumab or smaller HER2 binders to map HER2 across all metastases at once.","summary":"HER2 PET images HER2 across every metastasis at once using a radiolabelled HER2 binder, either 89Zr-trastuzumab or smaller 68Ga- and 18F-labelled affibodies and nanobodies such as 68Ga-ABY-025 and 18F-GE-226. The result is a whole-body receptor map rather than a single biopsy, which matters because HER2 expression varies between lesions. The ZEPHIR and IMPACT trials studied these tracers, and uptake was predictive of response to T-DM1. It is most useful in heterogeneous HER2-low disease, where one biopsy may be unrepresentative and HER2-directed ADCs now have indications. Studied since 2010, it is not yet approved; trials have been small, and full-antibody tracers need days between injection and imaging, which smaller binders aim to shorten. It shows how much HER2 each tumour deposit carries without a needle.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Gebhart et al., ZEPHIR: molecular imaging of heterogeneity in advanced HER2-positive breast cancer with 89Zr-trastuzumab PET (Annals of Oncology 2016)","url":"https://doi.org/10.1093/annonc/mdv577"}],"tags":[],"related":["f-18","ga-68","zr-89"],"indications":["breast-her2-positive"],"sections":[],"technologies":["pet","immuno-pet"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiolabelled HER2 binder; whole-body receptor map.","strengths":["Captures inter-lesion heterogeneity","Non-invasive re-assessment"],"limitations":["Not approved; small trials","Antibody tracers need days"],"since":2010,"route":"/technologies/her2-pet/"}
{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","aka":[],"tldr":"PET scans built from radiolabelled antibodies or their fragments, to see any protein an antibody can reach, including immune cells inside tumours.","summary":"Immuno-PET attaches long-lived positron emitters such as 89Zr or 64Cu to antibodies, minibodies or nanobodies, so that any protein an antibody can reach can be imaged across the whole body. It covers 89Zr-antibody imaging of ADC targets including TROP2 and HER2, and T-cell imaging with 89Zr-crefmirlimab berdoxam, a CD8 minibody, and 18F-AraG, which marks activated T cells. CD8 PET is in phase 2/3 as a pharmacodynamic and predictive biomarker for checkpoint inhibitors, aiming to show whether T cells are entering tumours early in treatment. The strengths are non-invasive imaging of target and immune infiltrate, and the fact that any antibody can be turned into a tracer. Full antibodies have slow kinetics, requiring days before imaging, and 89Zr is costly. Immuno-PET turns therapeutic antibodies into imaging agents that show where their targets and the immune cells are.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Bensch et al., 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade (Nature Medicine 2018)","url":"https://doi.org/10.1038/s41591-018-0255-8"}],"tags":[],"related":["f-18","cu-64","zr-89"],"indications":[],"sections":[],"technologies":["pet"],"targets":["trop2","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct"],"notes":[],"principle":"Long-lived positron emitters (89Zr, 64Cu) chelated to antibodies, minibodies, or nanobodies.","strengths":["Images target and immune infiltrate non-invasively","Any antibody can be turned into a tracer"],"limitations":["Slow kinetics for full antibodies","Cost of 89Zr"],"route":"/technologies/immuno-pet/"}
{"id":"in-vivo-dosimetry","kind":"technology","name":"In vivo dosimetry and patient-specific quality assurance","aka":[],"tldr":"Measuring the dose the patient actually receives, with detectors on the skin or the imaging panel behind them, to catch errors before they cause harm.","summary":"Radiotherapy accidents, though rare, have come from wrong plans, wrong patients and machine faults. Patient-specific quality assurance checks each complex plan on a phantom before the first treatment, and in vivo dosimetry measures the dose during treatment with diodes, thermoluminescent detectors or, increasingly, the electronic portal imaging device behind the patient, which reconstructs the delivered dose in three dimensions. Several countries require in vivo dosimetry by regulation; it is also central to safe FLASH and ultra-high-dose-rate research.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":["radiation-wave1"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Independent measurement of the delivered dose, compared with the planned dose, detects errors in planning, setup or machine output.","strengths":["Catches gross errors","Documents the dose actually given","Portal dosimetry needs no extra hardware"],"limitations":["Adds workload","Tolerance thresholds are debated","Cannot detect all error types"],"since":1990,"route":"/technologies/in-vivo-dosimetry/"}
{"id":"ldr-seed-brachytherapy","kind":"technology","name":"Low-dose-rate seed brachytherapy","aka":[],"tldr":"Dozens of rice-grain-sized radioactive seeds are implanted permanently in the prostate in a single procedure and deliver their dose over months.","summary":"Permanent seed implantation uses iodine-125 or palladium-103 seeds placed through the perineum under ultrasound guidance in a one-off outpatient procedure. It is a curative option for low- and favourable intermediate-risk prostate cancer with control matching surgery and external radiotherapy, and is used as a boost in higher-risk disease (the ASCENDE-RT trial). The same seeds treat some lung and pancreatic tumours at surgery, and plaque brachytherapy with similar isotopes treats uveal melanoma.","status":"established","asOf":"2026-09-17","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brachytherapy#Prostate_cancer"}],"tags":["radiation-wave1"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Permanently implanted low-activity sources deliver a continuous low dose rate over weeks to months, exploiting repair differences between tumour and normal tissue.","strengths":["Single procedure","Excellent long-term control in low-risk prostate cancer","Preserves continence for most"],"limitations":["Urinary symptoms for months","Not suitable for large glands or prior TURP","Radiation safety precautions after implant"],"since":1980,"route":"/technologies/ldr-seed-brachytherapy/"}
{"id":"lu177-radioligand-therapy","kind":"technology","name":"Lutetium-177 radioligand therapy","aka":["177Lu","Lu-177","Lutetium-177"],"tldr":"Cancer-seeking molecules carrying the radioactive metal lutetium-177, which delivers short-range radiation to tumours it binds; approved for neuroendocrine tumours and prostate cancer.","summary":"Lutetium-177 emits beta particles with a range of a few millimetres and gamma rays that allow imaging, making it the workhorse isotope of radioligand therapy. Lutathera (Lu-177 dotatate, approved 2018) targets somatostatin receptors on neuroendocrine tumours, and Pluvicto (Lu-177 PSMA-617, approved 2022) targets PSMA on prostate cancer; both improved outcomes in randomised trials. Supply of no-carrier-added lutetium, dosimetry and combinations with earlier lines of therapy are the current frontiers.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Lutetium-177","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Lutetium-177"}],"tags":[],"related":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","therapy-isotope-supply-chain"],"targets":["psma","sstr2"],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06184035","nct05547061"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["radioligand-therapy","therapy-isotope-supply-chain"],"notes":[],"principle":"A peptide or small molecule with high affinity for a tumour receptor is chelated to Lu-177 and infused; bound molecules irradiate the cell and its neighbours over the isotope's 6.6-day half-life.","strengths":["Randomised survival benefit in two diseases","Companion PET imaging selects patients","Tolerable toxicity profile"],"limitations":["Isotope supply and logistics","Marrow and kidney dose limits","Resistance and heterogeneous uptake"],"since":2018,"route":"/technologies/lu177-radioligand-therapy/"}
{"id":"medical-cyclotrons-synthesis-modules","kind":"technology","name":"Medical cyclotrons, hot cells, and synthesis modules","aka":[],"tldr":"The particle accelerators and shielded robotic chemistry boxes that make PET tracers in hospital basements and commercial pharmacies.","summary":"Compact 11-30 MeV cyclotrons from IBA (Cyclone), GE HealthCare (PETtrace, MINItrace), Siemens (Eclipse), ACSI (TR-24), and Sumitomo produce 18F, 68Ga, 64Cu, and 89Zr; shielded hot cells (Comecer, Von Gahlen, Tema Sinergie) house automated synthesis modules (Trasis AllinOne, IBA Synthera, GE FASTlab, Eckert & Ziegler Modular-Lab, Siemens Explora) that run GMP radiochemistry from cassettes. Solid-target 68Ga production is displacing generators at high-volume sites.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":["f-18","ga-68","cu-64","zr-89"],"indications":[],"sections":[],"technologies":["pet","radiopharmacy-network","pet-tracer-manufacturing","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":["iba","ge-healthcare","siemens-healthineers","trasis","comecer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Proton bombardment of enriched targets produces the isotope; cassette-based automated modules perform labelling, purification, and formulation behind lead shielding with QC before release.","strengths":["On-site supply of short-lived isotopes","Cassette chemistry standardises GMP production"],"limitations":["Capital and shielding cost ($2-5M per site)","Skilled radiochemists scarce","Site licensing takes years"],"route":"/technologies/medical-cyclotrons-synthesis-modules/"}
{"id":"medical-imaging-scanner-manufacturing","kind":"technology","name":"CT, MRI and PET scanner manufacturing","aka":[],"tldr":"The scanners that find and stage cancer are built by five companies in a dozen factories. Detectors, superconducting magnets and the helium that cools them are the parts that run short.","summary":"Computed tomography scanners are assembled around a rotating gantry carrying an X-ray tube and a detector arc of thousands of scintillator or, in the newest machines, cadmium telluride photon-counting elements; MRI systems around a superconducting magnet wound from niobium-titanium and cooled by liquid helium, with gradient coils and radiofrequency electronics; PET/CT around rings of lutetium-based scintillator crystals coupled to silicon photomultipliers. Siemens Healthineers builds CT in Forchheim and MRI in Erlangen, Germany, and PET/CT in Knoxville, Tennessee; GE HealthCare builds CT and PET in Waukesha, Wisconsin, and MRI in Florence, South Carolina, and makes the PETtrace cyclotron in Uppsala; Philips builds MRI in Best, in the Netherlands, and CT in Haifa, Israel; Canon Medical (the former Toshiba Medical) in Otawara, Japan; and United Imaging in Shanghai, which built the first total-body PET scanner with the University of California, Davis. The scanners then need siting, shielding, acceptance testing and service contracts, and their software is regulated as a medical device.\n\nSupply constraints are in the components. Helium shortages in 2022 and 2023 pushed makers toward sealed low-helium magnets (Philips BlueSeal, Siemens' sub-litre designs); lutetium oxyorthosilicate crystals and photon-counting detectors come from few sources; and X-ray tubes are made by the scanner companies and a small number of independents. Chinese makers now supply a large share of the domestic market, and the access gap in imaging tracks the radiotherapy gap. Recalls of scanners and their software are recorded in the FDA device recall database and national equivalents and are cited here only as a class. The image-guidance systems on linacs and the PET tracers that feed these scanners have their own records.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"FDA medical device recalls database","url":"https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfres/res.cfm"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CT_scan"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Physics_of_magnetic_resonance_imaging"}],"tags":["manufacturing-wave"],"related":[],"indications":[],"sections":[],"technologies":["ct","pet-ct","pet","spect","pet-tracer-manufacturing","medical-cyclotrons-synthesis-modules"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","canon-medical","united-imaging"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide manufacturing expansion","editedOn":"2026-09-17"},"principle":"Precision assembly of detectors, tubes, superconducting magnets and reconstruction software at a few global factories, dependent on a narrow set of materials.","strengths":["Five vendors compete on detectors and AI reconstruction","Total-body and photon-counting scanners are step changes","Long service life"],"limitations":["Helium and detector crystal supply","High capital cost limits low-income access","Service and software updates tie hospitals to the vendor"],"since":1972,"route":"/technologies/medical-imaging-scanner-manufacturing/"}
{"id":"mibg-theranostics","kind":"technology","name":"MIBG imaging and 131I-MIBG therapy","aka":[],"tldr":"A noradrenaline look-alike that neuroblastoma cells swallow: labelled with a small amount of radioactivity it shows the tumour on a scan; with a large amount it treats it.","summary":"123I-MIBG scintigraphy/SPECT is the standard staging scan (Curie score) in neuroblastoma, being partly replaced by 18F-MFBG PET. Therapeutic 131I-MIBG produces responses in ~30% of relapsed patients; COG ANBL1531 tested adding it to induction (results awaited). Also used in pheochromocytoma/paraganglioma (Azedra, discontinued 2024).","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Iobenguane","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iobenguane"}],"tags":[],"related":["f-18","i-123","i-131"],"indications":["neuroblastoma","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","spect","pet"],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Norepinephrine transporter (NET) uptake concentrates radio-iodinated MIBG in adrenergic tumours; 131I delivers beta radiation.","strengths":["Theranostic pair with decades of use","Targets NET-positive disease irrespective of GD2"],"limitations":["Prolonged isolation and radiation precautions in children","Myelosuppression requiring stem-cell support at high doses","Azedra withdrawal reduced supply"],"since":1985,"route":"/technologies/mibg-theranostics/"}
{"id":"nuclear-medicine-hardware","kind":"technology","name":"Nuclear medicine and total-body PET hardware","aka":[],"tldr":"Nuclear medicine hardware means the scanners themselves: PET/CT, SPECT/CT, and new total-body PET that images the whole body at once.","summary":"Siemens Healthineers (Biograph Vision Quadra), GE HealthCare (Omni Legend), United Imaging (uEXPLORER, uMI Panorama), Canon Medical (Cartesion Prime), and Positron/Mediso occupy the PET/CT market; SPECT/CT for dosimetry from Siemens, GE, and Spectrum Dynamics. Total-body and long-axial-field-of-view PET raise sensitivity roughly 40-fold, enabling low-dose, dynamic, and multi-tracer studies relevant to theranostics.","status":"established","asOf":"2026-09-08","links":[{"label":"Badawi et al., First human imaging studies with the EXPLORER total-body PET scanner (Journal of Nuclear Medicine 2019)","url":"https://doi.org/10.2967/jnumed.119.226498"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["pet-ct","spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","united-imaging","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Silicon photomultiplier detector rings with time-of-flight, coupled to CT for attenuation correction; long axial coverage captures the whole body in one bed position.","strengths":["Sensitivity and speed","Dosimetry for radioligand therapy"],"limitations":["Capital cost (total-body >$10M)","Data volume","Reimbursement not tied to sensitivity"],"route":"/technologies/nuclear-medicine-hardware/"}
{"id":"parp-pet","kind":"technology","name":"PARP PET","aka":[],"tldr":"A PET tracer that measures how much of the DNA repair enzyme PARP a tumour has, to predict response to PARP inhibitors.","summary":"PARP PET uses radiolabelled analogues of the PARP inhibitors olaparib and rucaparib, such as 18F-FluorThanatrace (FTT, Penn) and 18F-PARPi (MSK), which bind PARP1 in the nucleus and so measure both expression of the enzyme and drug engagement at the target. The rationale is that genomic HRD tests read a permanent scar, whereas a PARP tracer reports the tumour's current state. Trials in ovarian, breast and head-and-neck cancer test whether uptake predicts benefit from PARP inhibitors beyond BRCA and HRD status, and whether a fall in uptake on treatment confirms target engagement. It offers a direct pharmacodynamic readout that complements genomic HRD, but remains at the research stage and is available at only a few academic sites. It is a scan that measures how much of the DNA repair enzyme a tumour has, to predict whether a PARP inhibitor will work.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"Makvandi et al., A PET imaging agent for evaluating PARP-1 expression in ovarian cancer (Journal of Clinical Investigation 2018)","url":"https://doi.org/10.1172/JCI97992"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet"],"targets":["parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Radiolabelled olaparib or rucaparib analogues bind PARP1 in the nucleus.","strengths":["Direct pharmacodynamic readout","Complements genomic HRD"],"limitations":["Research stage","Limited to a few academic sites"],"route":"/technologies/parp-pet/"}
{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","aka":[],"tldr":"Like an ADC but with a small targeting peptide instead of an antibody, so it penetrates tumours faster and is cheaper to make.","summary":"Peptide-drug conjugates replace the antibody of an ADC with a short or bicyclic peptide that binds the target, giving rapid tumour penetration and renal clearance, with a short half-life that reduces systemic exposure and cheaper synthesis. Examples include melflufen (Pepaxto, withdrawn in the US), lutetium radioligands (technically peptide-radionuclide conjugates), and clinical-stage PDCs such as BT8009 zelenectide pevedotin, a Nectin-4 Bicycle toxin conjugate, and CBX-12, an exatecan-SMDC. Bicycle's zelenectide pevedotin is in phase 2/3 in urothelial cancer. The same short half-life that limits toxicity also limits tumour exposure, and renal toxicity is a class concern. The simple version is an ADC with a small peptide as the address label, faster to penetrate tumours and cheaper to make.","status":"approved","asOf":"2026-09-04","links":[{"label":"Cooper et al., Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (Chemical Society Reviews 2021)","url":"https://doi.org/10.1039/D0CS00556H"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":["nectin4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Short peptide or bicyclic peptide binds the target; short half-life reduces systemic exposure.","strengths":["Rapid penetration, renal clearance","Cheaper synthesis"],"limitations":["Short half-life limits tumour exposure","Renal toxicity"],"route":"/technologies/peptide-drug-conjugate/"}
{"id":"pet","kind":"technology","name":"PET (positron emission tomography)","aka":[],"tldr":"A scan that shows where a radioactive tracer accumulates, so it images what tumours are doing rather than what they look like.","summary":"Positron emission tomography detects the paired 511 keV gamma photons produced when a positron from a radioactive tracer annihilates with an electron; coincidence detection localises the source and the standardised uptake value (SUV) quantifies it. Isotopes such as 18F, 68Ga, 89Zr and 64Cu are attached to a targeting molecule, and the tracer determines what is measured: glucose metabolism (FDG), receptor expression (PSMA, SSTR, TROP2, HER2), stroma (FAP), immune cells (CD8) or DNA repair (PARP). In clinical use since 1975, it is almost always combined with CT or MRI for anatomic reference. Its strengths are whole-body biology in one quantitative scan and the fact that any target with a ligand can in principle be imaged. Resolution of about 4 mm and tracer supply and cost are the main limitations. PET images what tumours are doing rather than what they look like.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Positron_emission_tomography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Positron_emission_tomography"}],"tags":[],"related":["molecular-imaging-roadmap","f-18","ga-68","cu-64","zr-89"],"indications":[],"sections":[],"technologies":["fdg-pet","psma-pet","fapi-pet","trop2-pet","her2-pet","immuno-pet","parp-pet"],"targets":[],"drugs":["choline-c11"],"companies":["alpha-9-oncology","evergreen-theragnostics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05381103","nct06084806","nct03444844","nct07615101","nct06754085","nct06369831","nct04724369","nct07691775","nct07649122","nct06474806"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["nuclear-medicine-hardware","pet-tracer-manufacturing"],"notes":[],"principle":"Positron-emitting isotopes (18F, 68Ga, 89Zr, 64Cu) attached to a targeting molecule; coincidence detection of 511 keV photons; standardised uptake value (SUV) quantifies uptake.","strengths":["Whole-body biology in one scan","Quantitative","Any target with a ligand can in principle be imaged"],"limitations":["Resolution ~4 mm","Tracer supply and cost","Inflammation confounds FDG"],"since":1975,"route":"/technologies/pet/"}
{"id":"pet-adapted-therapy","kind":"technology","name":"PET-adapted (response-adapted) therapy","aka":[],"tldr":"Scan after two cycles of chemotherapy; if the tumour has gone dark, give less treatment, and if not, give more. Hodgkin lymphoma pioneered this.","summary":"Interim FDG-PET after cycle 2 (PET2) scored on the Deauville scale steers escalation or de-escalation: RATHL (omit bleomycin if PET2-negative, no loss of efficacy), HD18 (shorten escalated BEACOPP), HD16/HD17 and RAPID (omit radiotherapy in early stage if PET-negative, at a small PFS cost), and HD21/S1826 (PET-guided consolidation). Being extended to DLBCL and to ctDNA-adapted designs.","status":"standard-of-care","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05675410: AHOD2131 (COG / NCTN)","url":"https://clinicaltrials.gov/study/NCT05675410"},{"label":"ClinicalTrials.gov NCT02661503: GHSG HD21","url":"https://clinicaltrials.gov/study/NCT02661503"}],"tags":[],"related":[],"indications":["dlbcl"],"sections":[],"technologies":["fdg-pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"FDG-PET measures metabolic response early; Deauville ≥4 at PET2 predicts failure, allowing therapy to be tailored before completion.","strengths":["Spares most patients bleomycin, radiation or intensified chemotherapy","Identifies the minority who need escalation"],"limitations":["Interim PET has imperfect positive predictive value (many PET2-positive patients are cured anyway)","Omitting radiotherapy trades a few percent PFS for late-toxicity avoidance"],"since":2016,"route":"/technologies/pet-adapted-therapy/"}
{"id":"pet-ct","kind":"technology","name":"PET/CT","aka":[],"tldr":"PET and CT in one machine, so hot spots on the PET are pinned to exact locations on the CT.","summary":"PET/CT acquires PET and CT sequentially on one gantry; the CT provides attenuation correction for the PET data and pins each hot spot to an exact anatomical location. In clinical use since 2001, it is the default form of clinical PET and the standard for staging lymphoma, lung cancer, melanoma and head and neck cancer, combining anatomy with biology in one examination. Total-body PET/CT scanners such as the uEXPLORER and Biograph Vision Quadra image the whole body simultaneously with around 40 times the sensitivity of conventional scanners, enabling ultra-low-dose imaging and dynamic studies that follow tracer kinetics over time. The main drawback is that the CT adds radiation to the PET dose, which matters most in children and in patients scanned repeatedly. PET/CT is two scans in one machine so the biology shown by PET can be read against the anatomy shown by CT.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PET-CT","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PET-CT"}],"tags":[],"related":["molecular-imaging-roadmap","spect-ct"],"indications":[],"sections":[],"technologies":["pet","ct"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":["siemens-healthineers","ge-healthcare","united-imaging","canon-medical"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03444844","nct07615101","nct06754085","nct06369831","nct07691775","nct07649122"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-imaging"],"dependsOn":["pet","ct"],"notes":[],"principle":"Sequential PET and CT acquisition on one gantry; CT provides attenuation correction and anatomic localisation.","strengths":["Anatomy plus biology","Standard for lymphoma, lung, melanoma, head and neck staging"],"limitations":["CT radiation added to PET dose"],"since":2001,"route":"/technologies/pet-ct/"}
{"id":"pet-mri","kind":"technology","name":"PET/MRI","aka":[],"tldr":"PET combined with MRI instead of CT, giving biology plus the best soft-tissue detail, at lower radiation dose.","summary":"PET/MRI acquires PET and MRI simultaneously or sequentially using MR-compatible detectors, pairing PET's biological signal with MRI's superior soft-tissue contrast instead of CT. Because MRI adds no ionising radiation, the combined dose is lower than PET/CT, which is why it is valuable in paediatrics and in patients who need repeated scans. It is also used in brain tumours, prostate and pelvic cancers, where MRI already outperforms CT for local staging. In clinical use since 2010, it remains limited by cost, the small number of scanners and long acquisition times, and attenuation correction is harder than with CT because MRI does not directly measure tissue density. Whether the added detail changes management enough to justify the expense is still debated outside those niches. It is PET plus the best soft-tissue pictures, at lower radiation dose but with fewer machines available.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PET-MRI","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PET-MRI"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet"],"targets":[],"drugs":[],"companies":["siemens-healthineers","ge-healthcare","united-imaging"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet"],"notes":[],"principle":"PET and MRI are acquired simultaneously or sequentially with MR-compatible detectors.","strengths":["Lower radiation","Superior soft tissue"],"limitations":["Expensive, few scanners","Long acquisition"],"since":2010,"route":"/technologies/pet-mri/"}
{"id":"pet-tracer-manufacturing","kind":"technology","name":"PET tracer manufacturing and distribution","aka":[],"tldr":"Making PSMA, FDG, and new tracers under drug-manufacturing rules and delivering them daily.","summary":"FDA-approved PET drugs are made under cGMP at commercial radiopharmacies (PETNET, Cardinal Health, SOFIE, Jubilant, Curium) or academic sites under ANDA/NDA. New tracers (PSMA agents from Lantheus, Telix, Novartis; FES; FAPI in trials) rely on these networks for launch reach. Kits (Illuccix, Locametz) versus centrally produced doses (Pylarify) is a business-model divide.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["pet","psma-pet","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["petnet-solutions","cardinal-health","sofie-biosciences","lantheus","telix","jubilant-radiopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"Automated radiosynthesis modules, cassette-based chemistry, and rapid QC (radiochemical purity, endotoxin) before release.","strengths":["Daily national coverage in the US and Europe"],"limitations":["Tracer approval per site","Kit vs central-dose economics","Limited reach in low-income countries"],"route":"/technologies/pet-tracer-manufacturing/"}
{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","aka":[],"tldr":"A radioactive version of the hormone mimic used for the scan; it homes to neuroendocrine tumour cells and irradiates them from inside.","summary":"177Lu-DOTATATE (Lutathera; NETTER-1 second line, NETTER-2 first line in grade 2-3) is the reference. 177Lu-edotreotide (ITM-11, COMPETE: PFS 23.9 vs 14.1 months vs everolimus; FDA PDUFA 28 August 2026) is the second beta-emitter. Alpha PRRT with 212Pb-DOTAMTATE (AlphaMedix, Breakthrough designation; phase 2 ORR 54% in PRRT-naive) and 225Ac-DOTATATE (RYZ101, ACTION-1 phase 3) aims at beta-refractory disease. Antagonist ligands (177Lu-satoreotide) bind more receptor sites than agonists.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy"}],"tags":[],"related":["lu-177","ac-225","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","sstr-pet"],"targets":["sstr2"],"drugs":["lutathera","itm-11","alphamedix","ryz101"],"companies":["novartis","itm","orano-med","radiomedix","rayzebio"],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["radioligand-therapy","sstr-pet"],"notes":[],"principle":"An SSTR2-binding peptide is chelated to a therapeutic radionuclide and internalised by the tumour cell; beta (177Lu) or alpha (212Pb, 225Ac) emission; usually four cycles.","strengths":["Systemic, receptor-targeted","Response and quality-of-life benefit","Imaging selects and monitors"],"limitations":["Myelosuppression, rare MDS/AML (~2-3%)","Renal dose","Not curative; retreatment data limited"],"since":2018,"route":"/technologies/prrt/"}
{"id":"psma-pet","kind":"technology","name":"PSMA PET","aka":[],"tldr":"A prostate-cancer-specific PET scan that finds spread far earlier than CT or bone scan, and tells you whether a matched radioactive drug will work.","summary":"PSMA PET uses small-molecule urea-based ligands that bind the active site of prostate-specific membrane antigen and are internalised, labelled with 68Ga or 18F. Approved agents are 68Ga-PSMA-11 (Illuccix, Locametz), 18F-DCFPyL (Pylarify, with Pylarify TruVu approved in March 2026) and 18F-rhPSMA-7.3 (Posluma). In clinical use since 2020, it is standard for initial staging of high-risk disease and for biochemical recurrence, where it detects disease at PSA below 0.5 ng/mL, far earlier than CT or bone scan. It is also the theranostic gatekeeper: a PSMA-positive scan is required to select patients for 177Lu-PSMA-617, as in VISION and PSMAfore. Around 10% of patients have PSMA-negative disease, and uptake in ganglia and salivary glands can be mistaken for tumour. It finds spread early and predicts whether the matched radioactive drug will work.","status":"standard-of-care","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03392428: TheraP (ANZUP 1603)","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":[],"related":["f-18","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["pet","radioligand-therapy"],"targets":["psma"],"drugs":["choline-c11"],"companies":["clarity-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["pop-rt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct","radiopharmacy-network"],"notes":[],"principle":"Small-molecule urea-based ligands bind PSMA's active site and are internalised.","strengths":["Detects recurrence at PSA <0.5 ng/mL","Theranostic gatekeeper"],"limitations":["PSMA-negative disease in ~10%","Uptake in ganglia, salivary glands"],"since":2020,"route":"/technologies/psma-pet/"}
{"id":"quantitative-imaging-biomarkers","kind":"technology","name":"Quantitative imaging biomarkers (RECIST, PERCIST, SUV, ADC)","aka":["imaging biomarkers","response criteria","PERCIST","standardised uptake value","apparent diffusion coefficient","Deauville score","PI-RADS","QIBA"],"tldr":"The numbers pulled from scans that decide whether a cancer is shrinking, growing or dead: tumour diameters for RECIST, sugar uptake on PET, water movement on MRI; they run every trial and most clinic decisions, and they are only as good as the way the scan was taken.","summary":"What they measure. A scan is a picture, but a decision needs a number. Response criteria turn measurements into categories: RECIST 1.1 sums the longest diameters of up to five target lesions on CT or MRI and calls response, stable disease or progression from the percentage change; PERCIST does the same with the peak standardised uptake value of FDG on PET; the Deauville five-point scale reads FDG uptake in lymphoma against liver and blood pool; PI-RADS, LI-RADS and BI-RADS grade the probability of prostate, liver and breast cancer on multiparametric imaging; the apparent diffusion coefficient on diffusion MRI measures how freely water moves, which falls in dense tumour and rises when cells die; and dynamic contrast measures such as Ktrans track blood vessel leakiness. Radiomics adds hundreds of texture and shape features on top of these.\n\nWho uses them and what changes. Every oncology trial defines its endpoints with these criteria, so a RECIST progression call ends a treatment on trial and usually in clinic too. Deauville scores after two cycles decide escalation and de-escalation in Hodgkin lymphoma; PI-RADS decides who is biopsied; the Lugano criteria decide remission in lymphoma; PSMA-RADS and PERCIST are being written into radioligand and immunotherapy trials. Immunotherapy needed its own variant, iRECIST, because tumours can swell before they shrink.\n\nWhat limits them. Diameters ignore necrosis and cavitation; standardised uptake values shift with scanner, reconstruction, glucose level and time after injection; and readers disagree, which is why pivotal trials use blinded central review. The RSNA Quantitative Imaging Biomarkers Alliance publishes profiles setting the acquisition and analysis standards under which a measurement can be trusted to a stated precision. None of these measures needs new equipment; the cost is in standardising protocols and training readers.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"European Journal of Cancer 2009: New response evaluation criteria in solid tumours, revised RECIST guideline (version 1.1)","url":"https://doi.org/10.1016/j.ejca.2008.10.026"},{"label":"RSNA Quantitative Imaging Biomarkers Alliance (QIBA)","url":"https://www.rsna.org/research/quantitative-imaging-biomarkers-alliance"}],"tags":[],"related":[],"indications":["prostate","hcc"],"sections":[],"technologies":["radiomics","pet-adapted-therapy","fdg-pet","ct","pet","psma-pet","fes-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Standardised measurement of lesion size, tracer uptake, diffusion or perfusion on routinely acquired images, converted by validated criteria into response categories or risk scores with known reproducibility.","strengths":["Uses scans already acquired in routine care","Common language for trials and clinic","Standardisation profiles define achievable precision"],"limitations":["Size change lags biology and misses necrosis","Uptake and diffusion values vary with scanner and protocol","Reader disagreement, so trials need central review"],"since":2000,"route":"/technologies/quantitative-imaging-biomarkers/"}
{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","aka":[],"tldr":"Millions of tiny radioactive glass or resin beads are injected into the liver artery, lodging in the tumour and irradiating it from within.","summary":"Yttrium-90 microspheres (TheraSphere glass, SIR-Spheres resin) deliver beta radiation to hepatic tumours. Randomised trials versus sorafenib in advanced HCC (SARAH, SIRveNIB) were negative for OS but showed better tolerability and response; personalised dosimetry (DOSISPHERE-01) and radiation segmentectomy (LEGACY) established curative-intent use in early-stage disease. Standard alternative to TACE and a bridge or downstaging tool to transplant.","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy"}],"tags":[],"related":["y-90"],"indications":["hcc","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","spect"],"targets":[],"drugs":[],"companies":["sirtex","boston-scientific"],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Arterial delivery of 20-60 µm microspheres carrying 90Y (beta emitter, 2.5 mm mean path, 64 h half-life); dose planned from 99mTc-MAA mapping and lung shunt fraction.","strengths":["Outpatient, single session","Effective in portal vein thrombosis where TACE is contraindicated","Radiation segmentectomy can be curative for small tumours"],"limitations":["Radioembolisation-induced liver disease","Failed to beat sorafenib on OS in advanced disease","Lung shunting excludes some patients"],"since":2002,"route":"/technologies/radioembolisation-tare/"}
{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","aka":[],"tldr":"Attaching a radioactive atom to an antibody, so an ADC's targeting is used to deliver radiation instead of chemotherapy.","summary":"90Y-ibritumomab (Zevalin) and 131I-tositumomab proved the concept in lymphoma but were commercially abandoned. Renewed interest: 225Ac-labelled antibodies to PSMA (J591), CD33 (lintuzumab), DLL3, HER2, and 177Lu-labelled antibodies. Long antibody half-life is both a dosimetry advantage and a marrow-toxicity problem; pretargeting and fragment approaches address it.","status":"phase-2","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radioimmunotherapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radioimmunotherapy"}],"tags":["frontier"],"related":["idea-alpha-after-adc","lu-177","ac-225","i-131","y-90"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["psma","dll3","her2"],"drugs":[],"companies":["abdera-therapeutics","actinium-pharmaceuticals","convergent-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-biotherapy-and-radiopharmaceuticals"],"dependsOn":["therapy-isotope-supply-chain"],"notes":[],"principle":"A chelator-conjugated antibody or fragment carries 177Lu, 225Ac, 212Pb, or 131I.","strengths":["Any ADC target becomes a radiation target","Bystander crossfire independent of payload chemistry"],"limitations":["Marrow dose from circulating antibody","Manufacturing complexity"],"route":"/technologies/radioimmunotherapy/"}
{"id":"radioiodine-therapy","kind":"technology","name":"Radioiodine therapy and whole-body iodine scanning","aka":[],"tldr":"Using the thyroid's natural appetite for iodine to image and treat thyroid cancer with a radioactive form of it. The oldest theranostic, and now used more selectively than it was.","summary":"I-123 or low-activity I-131 scans map iodine-avid tissue; therapeutic I-131 ablates remnants or treats metastases. Randomised trials (HiLo, ESTIMABL1/2, IoN) have progressively reduced activity and then removed ablation for low-risk disease. Refractory disease (no uptake, or progression despite uptake) defines the population for kinase inhibitors; redifferentiation with MEK/BRAF inhibitors can restore uptake in selected patients.","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Isotopes_of_iodine#Iodine-131","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Isotopes_of_iodine#Iodine-131"}],"tags":[],"related":["i-123","i-131"],"indications":["thyroid"],"sections":[],"technologies":["radioligand-therapy","spect"],"targets":[],"drugs":["radioactive-iodine"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Thyroid cells take up iodine through the sodium-iodide symporter after TSH stimulation; the beta emission treats, the gamma emission images.","strengths":["Highly selective without any engineered targeting","Cheap, oral, curative in iodine-avid metastatic disease"],"limitations":["Dedifferentiated tumours lose uptake","Salivary toxicity; radiation precautions; second cancers at high cumulative activity"],"since":1946,"route":"/technologies/radioiodine-therapy/"}
{"id":"radioligand-dosimetry","kind":"technology","name":"Radioligand dosimetry","aka":[],"tldr":"Measuring, from scans taken after each dose, how much radiation a radioligand actually delivers to the tumour and to kidneys and marrow, so treatment can be personalised.","summary":"Radioligand therapies are mostly given at fixed activities, unlike external radiotherapy which is planned to a dose. Post-treatment SPECT or PET imaging at several time points lets physicists calculate absorbed doses to tumours and organs at risk, and trials are testing dose escalation guided by kidney and marrow dosimetry. European regulation now expects dosimetry to be available, and software and imaging protocols are being standardised to make it routine.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Dosimetry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["spect"],"notes":[],"principle":"Serial quantitative imaging after administration measures activity in organs over time; time-integrated activity and dose kernels give absorbed dose per organ, which guides subsequent cycles.","strengths":["Personalises activity to each patient","Explains variable toxicity and response","Required by European regulation"],"limitations":["Extra imaging visits","Methodological variation between centres","Prospective outcome evidence still limited"],"route":"/technologies/radioligand-dosimetry/"}
{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","aka":[],"tldr":"A drug that finds tumour cells and carries a radioactive atom that irradiates them from inside the body.","summary":"177Lu-DOTATATE (Lutathera, 2018) in neuroendocrine tumours and 177Lu-PSMA-617 (Pluvicto, 2022; pre-chemotherapy label 2025; 2026 label expansion) in prostate cancer are the approved beta-emitter therapies. Pipeline: 177Lu-FAP, 177Lu-PSMA-I&T, 177Lu-NeoB (GRPR), 177Lu-labelled antibodies. Dosimetry-guided personalised dosing is emerging.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radioligand_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radioligand_therapy"}],"tags":[],"related":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["psma-pet","spect","targeted-alpha-therapy"],"targets":["psma","sstr2","fap"],"drugs":["pluvicto","lutathera"],"companies":["clarity-pharmaceuticals","abdera-therapeutics","alpha-9-oncology","ariceum-therapeutics","artbio","atomic-alchemy","evergreen-theragnostics","mariana-oncology","nucleus-radiopharma","point-biopharma","precirix","radionetics-oncology","ratio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-biotherapy-and-radiopharmaceuticals"],"dependsOn":["therapy-isotope-supply-chain","radiopharmacy-network","medical-cyclotrons-synthesis-modules","pet-ct","radioligand-dosimetry"],"notes":[],"principle":"177Lu emits beta particles with ~2 mm range and gamma photons for SPECT imaging; the ligand determines biodistribution.","strengths":["Systemic, whole-body targeting of microscopic disease","Crossfire kills antigen-negative neighbours","Imaging companion selects patients"],"limitations":["Marrow and kidney dose","Isotope logistics (6.7-day half-life)","Not curative alone"],"since":2018,"route":"/technologies/radioligand-therapy/"}
{"id":"radiomics","kind":"technology","name":"Radiomics","aka":[],"tldr":"Turning ordinary CT, MRI and PET scans into hundreds of measured features of shape and texture that computers relate to tumour biology and outcome.","summary":"Radiomics, a term coined in 2012, extracts quantitative descriptors of intensity, shape and texture from medical images and links them to diagnosis, prognosis or treatment response. Radiogenomics goes a step further by relating imaging phenotypes to tumour mutations and expression. Reproducibility across scanners and protocols has been the main obstacle, addressed by the Image Biomarker Standardisation Initiative and by deep-learning models trained end to end.","status":"emerging","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Radiomics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiomics"}],"tags":[],"related":["quantitative-imaging-biomarkers"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Segment the tumour, compute standardised feature sets or learned representations, then fit predictive models validated on external cohorts.","strengths":["Uses images already acquired in routine care","Whole-tumour and longitudinal view without a biopsy","Can complement genomics where tissue is scarce"],"limitations":["Features vary with scanner and reconstruction","Many published signatures fail external validation","Few prospective trials"],"route":"/technologies/radiomics/"}
{"id":"radionuclide-generators-kits","kind":"technology","name":"Radionuclide generators and cold kits","aka":[],"tldr":"Bench-top devices that 'milk' a short-lived isotope from a long-lived parent, plus vials of ready-to-label ligand. How most hospitals make PSMA and somatostatin PET tracers without a cyclotron.","summary":"Ge-68/Ga-68 generators (Eckert & Ziegler GalliaPharm, IRE ELiT Galli Eo, ITG) elute Ga-68 for 6-12 months; Mo-99/Tc-99m generators (Curium, Lantheus, GE) underpin SPECT; kits such as Illuccix and Gozellix (Telix), Locametz (Novartis) and NETSPOT (Novartis/AAA) let a radiopharmacy label PSMA-11 or DOTATATE in minutes. Generator supply shortages (Ge-68 in 2018-19) and kit versus unit-dose economics shape tracer access.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211"}],"tags":["supporting"],"related":["ga-68","tc-99m","mo-99","ge-68"],"indications":[],"sections":[],"technologies":["psma-pet","pet-tracer-manufacturing","medical-cyclotrons-synthesis-modules","spect"],"targets":[],"drugs":[],"companies":["eckert-ziegler","curium","telix","novartis","lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Parent isotope adsorbed on a column decays to the daughter, which is eluted on demand; cold kits contain lyophilised chelator-ligand and buffer for one-step labelling.","strengths":["Cyclotron-free access to PET tracers","Decentralised, low-cost labelling"],"limitations":["Limited activity per elution (few patients per day)","Generator supply concentrated in a few producers","Regulatory status of kits varies by country"],"route":"/technologies/radionuclide-generators-kits/"}
{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","aka":[],"tldr":"Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes.","summary":"Radioligand therapy kills by DNA damage, so blocking repair should amplify it. Early-phase studies combine 177Lu-PSMA with olaparib in prostate cancer and 177Lu-DOTATATE with PARP inhibitors in neuroendocrine tumours; the recurring question is whether marrow toxicity rises faster than tumour control. No phase 3 had read out by 2026.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: Lu-177 PSMA plus olaparib","url":"https://clinicaltrials.gov/search?term=lutetium%20PSMA%20olaparib"}],"tags":["frontier","promising"],"related":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["parp","psma","sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Beta or alpha decay produces single- and double-strand breaks; PARP or ATR inhibition prevents repair, converting sublethal damage into cell death and lowering the activity required.","strengths":["Rational and mechanism-driven","Both components already approved separately","Could reduce the number of radioligand cycles"],"limitations":["Overlapping haematologic toxicity","Optimal sequencing and timing unknown","No randomised evidence yet"],"route":"/technologies/radionuclide-parp-combination/"}
{"id":"radiopharmaceutical-gmp-release","kind":"technology","name":"Radiopharmaceutical GMP and releasing a drug that decays","aka":[],"tldr":"A radioactive medicine loses activity every hour, so it is made to order, tested in hours and often injected before the sterility test has finished. The rules for that are different from ordinary drugs, and the handful of plants that make lutetium therapies have had their own shortages.","summary":"Radiopharmaceuticals are made under GMP frameworks written for their half-lives: 21 CFR 212 for PET drugs in the United States (with USP chapters 823 and 825 for compounding and nuclear pharmacy), 21 CFR 211 for therapeutic radiopharmaceuticals, and EU GMP Annex 3. Each batch is calibrated to a stated activity at a stated time, tested for radionuclidic purity (for example lutetium-177m in carrier-added lutetium-177), radiochemical purity (how much of the isotope is actually attached to the ligand), pH, endotoxin and appearance, and released within hours; the regulations allow release before the fourteen-day sterility test is complete because the product would otherwise have decayed, with the test finished retrospectively. Shelf life is measured in hours for PET tracers and a few days for lutetium products, so manufacture is scheduled against a named patient's appointment and the dose is shipped in a shielded container the same day.\n\nTherapeutic radioligands are made centrally. Novartis produces lutetium-177 dotatate and lutetium-177 vipivotide tetraxetan at plants in Millburn and Indianapolis in the United States, Zaragoza in Spain and Ivrea in Italy, and in 2022 paused Ivrea and Millburn over potential quality issues, then in 2023 limited new patient starts in the United States until the Indianapolis site was licensed and lutetium supply caught up. Curium, ITM, Telix and Lantheus run or contract their own radiopharmaceutical plants and radiopharmacy networks. Because any delay means a missed treatment rather than a late shipment, the sector has argued for regional radiopharmacy hubs and harmonised transport rules, ideas recorded elsewhere on this site.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"},{"label":"EU GMP Annex 3: manufacture of radiopharmaceuticals","url":"https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiopharmaceutical"}],"tags":["manufacturing-wave"],"related":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["therapy-isotope-supply-chain","radiopharmacy-network","pet-tracer-manufacturing","research-reactor-isotope-production","cyclotron-isotope-production","radioligand-therapy","radioligand-dosimetry"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it","radium-223","ga68-dotatate"],"companies":["novartis","curium","itm","telix","lantheus","bayer","petnet-solutions","cardinal-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide manufacturing expansion","editedOn":"2026-09-17"},"principle":"Time-stamped activity, rapid quality control and conditional release before sterility results, under GMP annexes written for half-lives of hours to days.","strengths":["Clear regulatory frameworks in the US and EU","Quality control fits within the half-life","Central plants give consistent product"],"limitations":["Missed slots are lost doses","Few licensed therapeutic plants","Cross-border transport of radioactive material"],"since":2011,"route":"/technologies/radiopharmaceutical-gmp-release/"}
{"id":"radiopharmacy-network","kind":"technology","name":"Radiopharmacy and cyclotron networks","aka":[],"tldr":"The factories and courier routes that make and deliver short-lived radioactive tracers to hospitals within hours.","summary":"PET tracers (18F, half-life 110 minutes) are produced in regional cyclotron pharmacies and driven or flown to scanners the same day; 68Ga comes from generators or cyclotrons on site; 177Lu and 225Ac therapies are made centrally and shipped globally against decay. Networks: PETNET (Siemens), Cardinal Health, SOFIE, Curium, Jubilant Radiopharma, Isologic/Isorad in Canada, with regional players in Europe and Asia. Capacity and licensing of nuclear pharmacies limits where radioligand therapy can be given.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"21 CFR Part 212: current good manufacturing practice for PET drugs","url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-212"}],"tags":["supporting"],"related":["f-18","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["pet","psma-pet","radioligand-therapy","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":["petnet-solutions","cardinal-health","sofie-biosciences","curium","jubilant-radiopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["medical-cyclotrons-synthesis-modules"],"notes":[],"principle":"Cyclotron proton bombardment or generator elution produces the isotope; automated synthesis modules label the ligand; QC release within an hour; timed logistics deliver a calibrated activity.","strengths":["Same-day supply of 18F tracers across most high-income regions","Established GMP frameworks"],"limitations":["Rural and low-income coverage gaps","Therapy isotope logistics against decay","Single points of failure in reactor supply"],"route":"/technologies/radiopharmacy-network/"}
{"id":"research-reactor-isotope-production","kind":"technology","name":"Research reactors for medical isotopes (Mo-99, Lu-177, I-131)","aka":[],"tldr":"Most of the world's therapeutic and scanning isotopes are made by putting targets into about half a dozen ageing research reactors and flying the product out within days. When two reactors were down at once in 2009 and 2010, hospitals worldwide ran short of the most used scan isotope.","summary":"Neutron-rich isotopes come from reactors. Molybdenum-99, parent of technetium-99m for most bone and SPECT scans, is made by fissioning uranium targets; lutetium-177 for radioligand therapy is made either directly by irradiating enriched lutetium-176 (carrier-added, with a long-lived Lu-177m impurity that complicates waste) or indirectly by irradiating enriched ytterbium-176 and chemically separating the lutetium that grows in (non-carrier-added, the route used by ITM, SHINE, Isotopia and others); iodine-131 comes from tellurium targets or fission. The irradiations happen in a small fleet of high-flux research reactors: BR2 at SCK CEN in Mol (Belgium), the High Flux Reactor at Petten (Netherlands), MARIA (Poland), LVR-15 (Czech Republic), SAFARI-1 at Pelindaba (South Africa), OPAL at Lucas Heights (Australia), MURR in Missouri and reactors in Russia. Processors such as Curium, IRE, NTP and ANSTO dissolve the targets in hot cells and ship purified product to generator and radiopharmaceutical makers; lutetium producers such as ITM, Isotopia, Eckert & Ziegler and Curium buy irradiation time and do the separation. Bruce Power in Ontario has shown that a commercial power reactor can irradiate ytterbium targets for ITM, opening a new class of supplier.\n\nThe fleet is old and outages coincide. When Canada's NRU reactor shut unexpectedly in 2009 and Petten's HFR followed in 2010, the world lost most of its Mo-99 for months; the OECD Nuclear Energy Agency's high-level group on medical radioisotopes was formed in response, pressed for full-cost pricing, scheduled reserve capacity and conversion of targets from highly enriched to low-enriched uranium (SAFARI-1 converted first), and still tracks the supply. NRU stopped isotope production in 2016 and closed in 2018; the Pallas reactor being built at Petten is the planned replacement for the HFR. Newer constraints are enriched ytterbium-176, most of which has historically come from Russian enrichment, and the surge in lutetium demand since lutetium-177 vipivotide tetraxetan was approved, which produced dose delays in 2022 and 2023.","status":"standard-of-care","asOf":"2026-09-17","links":[{"label":"OECD Nuclear Energy Agency: supply of medical radioisotopes","url":"https://www.oecd-nea.org/jcms/pl_20168/medical-radioisotopes"},{"label":"US DOE Isotope Program","url":"https://www.isotopes.gov/"},{"label":"Wikipedia: technetium-99m and the Mo-99 supply crisis","url":"https://en.wikipedia.org/wiki/Technetium-99m#Shortages"}],"tags":["manufacturing-wave"],"related":["tc-99m","mo-99","lu-177","i-131"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["therapy-isotope-supply-chain","radionuclide-generators-kits","cyclotron-isotope-production","radiopharmaceutical-gmp-release","radiopharmacy-network","radioligand-therapy","spect"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it"],"companies":["curium","ire","ntp-radioisotopes","ansto","itm","isotopia","eckert-ziegler","nordion","shine-technologies","northstar-medical-radioisotopes","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide manufacturing expansion","editedOn":"2026-09-17"},"principle":"Neutron capture or fission in high-flux research reactors, followed by hot-cell chemistry and same-week logistics for isotopes with half-lives of days.","strengths":["Large activities per irradiation","Well characterised routes with pharmacopoeial monographs","Power reactors can now add capacity"],"limitations":["Half a dozen ageing reactors with coinciding outages","Enriched target material from few sources","Transport of short-lived product across borders"],"since":1960,"route":"/technologies/research-reactor-isotope-production/"}
{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","aka":[],"tldr":"Site-specific conjugation and linker chemistry decide exactly where and how many payloads attach to the antibody, which determines how safe and effective an ADC is.","summary":"Random lysine or cysteine conjugation (T-DM1, brentuximab) gives heterogeneous mixtures. Engineered cysteines (THIOMAB), glycan remodelling (Synaffix GlycoConnect), enzymatic (sortase, transglutaminase), and non-natural amino acids (Ambrx, Sutro) yield homogeneous DAR. Hydrophilic linkers (Mersana Dolaflexin, Zymeworks ZD06519 platform, MediLink TMALIN) allow DAR 8 without aggregation; cleavable tetrapeptide GGFG (DXd) versus non-cleavable SMCC (T-DM1) governs bystander effect.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bioconjugation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bioconjugation"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Defined attachment sites and linker hydrophilicity control pharmacokinetics, aggregation, and payload release.","strengths":["Homogeneous product, better PK","Enables high DAR and dual payloads"],"limitations":["Manufacturing complexity"],"route":"/technologies/site-specific-conjugation/"}
{"id":"spect","kind":"technology","name":"SPECT & bone scan","aka":[],"tldr":"SPECT and the bone scan are an older type of nuclear scan, still used for bone metastases and to check where a radioactive drug went after treatment.","summary":"SPECT uses gamma cameras to detect single photons from isotopes such as 99mTc, 111In and 177Lu, rotating around the patient to reconstruct a 3D distribution. The 99mTc-MDP bone scan is its most familiar oncology use, detecting skeletal metastases through increased bone turnover, although PSMA PET is displacing it in prostate cancer. Its growing role is in theranostics: SPECT/CT after 177Lu therapy shows where the radioligand went and enables post-treatment dosimetry, a key enabler of personalised radioligand dosing. It is cheap and widespread, but its resolution and sensitivity are lower than PET, and standardising dosimetry protocols across centres remains work in progress. SPECT is the older nuclear scan still used for bone metastases and for checking where a radioactive drug ended up.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography"}],"tags":[],"related":["radioligand-dosimetry","spect-ct","tc-99m","in-111","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":["atomic-alchemy","ge-healthcare","siemens-healthineers","mediso"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["nuclear-medicine-hardware","radionuclide-generators-kits"],"notes":[],"principle":"Gamma cameras detect single photons from 99mTc, 111In, 177Lu; rotating acquisition reconstructs 3D distribution.","strengths":["Cheap, widespread","Dosimetry for radioligand therapy"],"limitations":["Lower resolution and sensitivity than PET"],"route":"/technologies/spect/"}
{"id":"spect-ct","kind":"technology","name":"SPECT/CT","aka":[],"tldr":"A gamma camera with a CT scanner bolted on, so a hot spot on a bone scan or a sentinel-node scan is pinned to the exact bone or lymph node, and the dose from a radioactive drug can be measured after treatment.","summary":"SPECT/CT acquires a rotating gamma-camera study and a CT scan on one gantry. The CT corrects the SPECT for attenuation and places each focus of tracer anatomically, turning an ambiguous spot on a planar bone scan into a rib fracture or a metastasis and mapping a sentinel node to the correct basin before surgery. In oncology it is used for technetium bone scans in prostate and breast cancer, sentinel lymph node mapping in melanoma and breast cancer, radioiodine scans in thyroid cancer, MIBG in neuroblastoma, somatostatin-receptor scans where PET is not available and, increasingly, for quantitative imaging of lutetium-177 after radioligand therapy so the absorbed dose to tumour and kidneys can be calculated. Newer cameras replace sodium iodide crystals with cadmium zinc telluride detectors arranged in a ring (GE StarGuide, Siemens Symbia Pro.specta with digital detectors), which are faster and more quantitative.\n\nSPECT is cheaper and far more widely available than PET, and the tracers are generator-produced without a cyclotron, but its resolution and sensitivity are lower and scans are slower.","status":"standard-of-care","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography","links":[{"label":"Wikipedia: SPECT","url":"https://en.wikipedia.org/wiki/Single-photon_emission_computed_tomography"},{"label":"GE HealthCare: SPECT/CT systems","url":"https://www.gehealthcare.com/products/molecular-imaging/spect-ct"}],"tags":["machines-wave"],"related":["radioligand-therapy","pet-ct","lu-177"],"indications":["prostate","thyroid","neuroblastoma","neuroendocrine"],"sections":[],"technologies":["spect","ct","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":["ge-healthcare","siemens-healthineers","mediso"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Rotating gamma cameras record single photons from technetium-99m, iodine-123 or lutetium-177 tracers; a co-registered CT provides attenuation correction and anatomical localisation for a quantitative three-dimensional map.","strengths":["Widely available and cheaper than PET","Tracers from generators, no cyclotron needed","Dosimetry after lutetium-177 therapy"],"limitations":["Lower resolution and sensitivity than PET","Slower acquisitions","Fewer targeted tracers than PET"],"since":1999,"route":"/technologies/spect-ct/"}
{"id":"sstr-pet","kind":"technology","name":"Somatostatin receptor PET (68Ga/64Cu-DOTATATE)","aka":[],"tldr":"A PET scan using a radioactive hormone mimic that lights up neuroendocrine tumours and shows whether the matching radioactive treatment will work.","summary":"68Ga-DOTATATE (Netspot, 2016), 68Ga-DOTATOC (2019) and 64Cu-DOTATATE (Detectnet, 2020) replaced 111In-octreotide scintigraphy, with far higher sensitivity for small lesions and bone disease. Mandatory for staging, for selecting patients for PRRT (Krenning score ≥3 or uptake above liver), and for detecting occult primaries. FDG PET complements it in high-grade or dedifferentiated disease ('flip-flop' pattern).","status":"standard-of-care","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/DOTA-TATE","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DOTA-TATE"}],"tags":[],"related":["ga-68","in-111","cu-64"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":["pet","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["pet-ct","radionuclide-generators-kits"],"notes":[],"principle":"Radiolabelled somatostatin analogue binds SSTR2 on tumour cells; positron emission imaged by PET/CT.","strengths":["Whole-body receptor map","Theranostic gatekeeper for 177Lu-DOTATATE","Changes management in ~40% of patients versus conventional imaging"],"limitations":["Physiologic uptake in pancreas uncinate, spleen, pituitary","Poor sensitivity in SSTR-negative high-grade disease","68Ga generator supply and short half-life"],"since":2016,"route":"/technologies/sstr-pet/"}
{"id":"sterile-fill-finish","kind":"technology","name":"Sterile fill-finish and lyophilisation","aka":[],"tldr":"Sterile fill-finish is putting the finished drug into vials under sterile conditions. It is a frequent cause of shortages when capacity is tight.","summary":"Fill-finish capacity for biologics, ADCs, and radiopharmaceutical kits is concentrated (Catalent, Vetter, Baxter BioPharma Solutions, Thermo Fisher, Lonza, Samsung Biologics); lyophilisation is common for ADCs and mRNA products. Shortages of cisplatin and carboplatin in 2023 traced to a single sterile injectables plant (Intas/Accord) failing inspection, exposing the fragility of generic oncology supply.","status":"standard-of-care","asOf":"2026-09-08","links":[{"label":"FDA guidance: sterile drug products produced by aseptic processing","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Fill-finish relies on aseptic filling in isolators, lyophilisation cycles tuned to product stability, and 100% container-closure integrity inspection.","strengths":["Established GMP"],"limitations":["Concentrated capacity","Generic injectable shortages","Long qualification times"],"route":"/technologies/sterile-fill-finish/"}
{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","aka":[],"tldr":"Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage.","summary":"Actinium-225 and lead-212 agents (225Ac-PSMA-617, 225Ac-DOTATATE/RYZ101, 212Pb-DOTAMTATE/AlphaMedix, 225Ac-FAP) are in phase 3. Radium-223 (Xofigo) is the only approved alpha emitter, for bone metastases. Isotope supply (TerraPower, Orano, ITM) is the binding constraint. Alpha therapy after beta failure produces responses in PSMA-refractory disease.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy"}],"tags":["frontier"],"related":["astatine-211-alpha-therapy","ac-225","ra-223","pb-212"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma","sstr2","fap"],"drugs":[],"companies":["terrapower-isotopes","orano-med","itm","rayzebio","fusion-pharma","abdera-therapeutics","actinium-pharmaceuticals","alpha-9-oncology","ariceum-therapeutics","artbio","convergent-therapeutics","ratio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["therapy-isotope-supply-chain","radiopharmacy-network","radioligand-dosimetry"],"notes":[],"principle":"Alpha particles (4-9 MeV, <100 µm range) cause clustered double-strand breaks independent of oxygen and cell cycle.","strengths":["Overcomes beta resistance","Kills micrometastases with minimal crossfire"],"limitations":["Ac-225 supply","Daughter-nuclide redistribution (salivary, renal toxicity)","Dosimetry difficult"],"route":"/technologies/targeted-alpha-therapy/"}
{"id":"therapy-isotope-supply-chain","kind":"technology","name":"Therapeutic isotope supply chain (Mo-99, Lu-177, Ac-225)","aka":[],"tldr":"Where the radioactive atoms for imaging and therapy actually come from: ageing reactors, new accelerators, and a scramble for actinium.","summary":"Mo-99/Tc-99m for SPECT still depends on a few research reactors (BR2, HFR Petten, OPAL, SAFARI) with accelerator alternatives from NorthStar and SHINE. Lu-177 (non-carrier-added) is supplied by ITM, SHINE, Eckert & Ziegler, Curium and NorthStar; Ac-225 supply is the binding constraint for alpha therapy, with US DOE, TerraPower Isotopes, Orano Med (Pb-212), NorthStar, Niowave, and ITM expanding. Supply agreements are now a competitive asset for radiopharma companies.","status":"established","asOf":"2026-09-08","links":[{"label":"US Department of Energy Isotope Program","url":"https://www.isotopes.gov/"}],"tags":["supporting"],"related":["tc-99m","mo-99","lu-177","ac-225","pb-212"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["itm","terrapower-isotopes","orano-med","northstar-medical-radioisotopes","shine-technologies","eckert-ziegler","curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Reactor neutron capture (Lu-176→Lu-177), Th-229 decay chains and accelerator spallation (Ac-225), and electron-accelerator photonuclear routes (Mo-99) produce isotopes that are purified, calibrated, and shipped against decay.","strengths":["Multiple new non-reactor routes since 2020"],"limitations":["Ac-225 shortage until late 2020s","Reactor outages cause global shortages","Regulatory licensing of new production sites is slow"],"route":"/technologies/therapy-isotope-supply-chain/"}
{"id":"total-body-pet-screening","kind":"technology","name":"Total-body PET for screening and ultra-low-dose imaging","aka":[],"tldr":"Scanners sensitive enough to image the whole body in seconds at a fraction of the radiation dose, which raises the question of whether healthy people should be scanned at all.","summary":"Total-body PET systems capture the entire body in one field of view with roughly forty times the sensitivity of conventional scanners, enabling minute-long scans, tracer doses a fraction of the usual, and dynamic whole-body kinetics. That makes asymptomatic screening technically conceivable for the first time, but there is no evidence of mortality benefit, and incidentalomas, cost and radiation argue against it. The near-term value is in dosimetry, paediatrics and pharmacokinetic research.","status":"concept","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: total-body PET","url":"https://clinicaltrials.gov/search?term=total-body%20PET"}],"tags":["frontier"],"related":[],"indications":[],"sections":[],"technologies":["pet-ct","pet"],"targets":[],"drugs":[],"companies":["united-imaging","siemens-healthineers"],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A long axial field-of-view detector ring captures far more of the emitted photons, letting sensitivity be traded for dose, time, or both.","strengths":["Ultra-low-dose or ultra-fast scans","Whole-body kinetic modelling for radioligand dosimetry","Better paediatric and repeat imaging"],"limitations":["No screening evidence and likely overdiagnosis","Scanner cost limits access","Tracer supply and reimbursement"],"route":"/technologies/total-body-pet-screening/"}
{"id":"trop2-pet","kind":"technology","name":"TROP2 PET","aka":[],"tldr":"An experimental PET scan that shows whether a tumour carries the TROP2 protein, so doctors could pick the right ADC before giving it.","summary":"89Zr-labelled anti-TROP2 antibodies and 68Ga/18F-labelled TROP2 nanobodies and peptides (Fudan University, Peking Union, others) have been imaged in first-in-human studies in breast, lung, and pancreatic cancer. The goal is non-invasive, whole-body, heterogeneity-aware selection and monitoring for sacituzumab govitecan, datopotamab deruxtecan, and sacituzumab tirumotecan, where IHC has been an unreliable predictor.","status":"phase-1","asOf":"2026-09-04","links":[],"tags":["frontier"],"related":["f-18","ga-68","zr-89"],"indications":[],"sections":[],"technologies":["pet","immuno-pet"],"targets":["trop2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A radiolabelled TROP2 binder is imaged; antibody tracers image at 3-6 days with 89Zr, nanobodies within 1-2 hours with 68Ga/18F.","strengths":["Whole-body target map","Could resolve intratumoural heterogeneity","Repeatable on progression"],"limitations":["Early stage; no validated SUV cut-off","Antibody tracers are slow; nanobodies have renal uptake","Unclear whether expression level predicts ADC response"],"since":2023,"route":"/technologies/trop2-pet/"}
{"id":"b7h3","kind":"target","name":"B7-H3","aka":[],"tldr":"B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.","summary":"B7-H3 (CD276) is an immune checkpoint-like molecule broadly overexpressed in solid tumours with limited normal expression; its function is debated, inhibiting T-cell activation and promoting tumour cell migration. Expression is more homogeneous than many ADC targets, found in 60-70% of small-cell lung cancer and 80-90% of castration-resistant prostate cancer by IHC, as well as head and neck and paediatric solid tumours. Ifinatamab deruxtecan (I-DXd) has shown high response rates in small-cell lung cancer and is in phase 3. B7-H3 is also pursued with radioligands and CAR-T. Whether its immune-dampening role means antibodies against it add an immunological benefit beyond payload delivery is unresolved. The simple version is a widely present tumour surface protein now used mainly as an address for ADCs.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD276","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD276"}],"tags":["adc-target"],"related":[],"indications":["sclc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CD276","hgnc":"HGNC:19137","ensembl":"ENSG00000103855","uniprot":"Q5ZPR3","entrez":"80381","biology":"Function debated: inhibits T-cell activation, promotes tumour cell migration. Expression is more homogeneous than many ADC targets.","whereFound":["Small-cell lung cancer","Prostate","Head and neck","Paediatric solid tumours"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"sclc","pct":"60-70","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/CD276"},{"indicationId":"prostate","pct":"80-90","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/CD276","note":"Castration-resistant disease"}],"route":"/targets/b7h3/"}
{"id":"cd20","kind":"target","name":"CD20","aka":[],"tldr":"CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.","summary":"CD20 (MS4A1) is a B-cell tetraspanin that regulates calcium flux; it is not internalised, which favours effector-based antibodies and T-cell engagers over ADCs, and it is present on over 95% of DLBCL and, more dimly, over 90% of CLL. It is the target of rituximab, the first antibody approved for cancer in 1997, and of obinutuzumab. The CD20×CD3 bispecifics glofitamab, epcoritamab, mosunetuzumab, and odronextamab now offer off-the-shelf T-cell redirection in lymphoma without the manufacturing wait of CAR-T. Loss of CD20 expression is a recognised escape route after repeated anti-CD20 therapy, and the best sequencing of bispecifics versus CAR-T is still being worked out. The simple version is the B-cell marker that started antibody therapy for cancer and now anchors the newest T-cell engagers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD20","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD20"}],"tags":["antibody-target"],"related":[],"indications":["dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":["ibritumomab-tiuxetan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MS4A1","hgnc":"HGNC:7315","ensembl":"ENSG00000156738","uniprot":"P11836","entrez":"931","biology":"CD20 is a tetraspanin regulating B-cell calcium flux; it is not internalised, favouring effector-based antibodies over ADCs.","whereFound":["DLBCL","Follicular lymphoma","CLL","Mantle cell lymphoma"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"dlbcl","pct":">95","measure":"Surface expression","source":"https://en.wikipedia.org/wiki/CD20"}],"route":"/targets/cd20/"}
{"id":"ceacam5","kind":"target","name":"CEACAM5","aka":[],"tldr":"The classic 'CEA' tumour marker measured in blood, also present on the cell surface where ADCs can reach it.","summary":"CEACAM5 is carcinoembryonic antigen, a GPI-anchored adhesion molecule that is shed into circulation as the serum CEA marker and also sits on the cell surface where ADCs and T-cell engagers can reach it. It is overexpressed in colorectal (80-90% moderate-to-high by IHC), gastric (50-60%), lung adenocarcinoma, and pancreatic cancers; only 20-25% of non-squamous NSCLC met the high-expression threshold used in CARMEN. Tusamitamab ravtansine failed in phase 3 NSCLC (CARMEN-LC03), a setback that raised questions about payload choice and patient selection rather than the target itself. CEACAM5 remains pursued with T-cell engagers and next-generation ADCs. The simple version is the classic CEA blood marker, now also being used as a surface target for drug delivery.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Carcinoembryonic_antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoembryonic_antigen"}],"tags":["adc-target","biomarker"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CEACAM5","hgnc":"HGNC:1817","ensembl":"ENSG00000105388","uniprot":"P06731","entrez":"1048","biology":"GPI-anchored adhesion molecule; shed into circulation as the serum CEA marker.","whereFound":["Colorectal","Gastric","Lung adenocarcinoma","Pancreatic"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/ceacam5/"}
{"id":"cxcr4","kind":"target","name":"CXCR4","aka":[],"tldr":"A chemokine receptor that anchors blood cells in the marrow and helps cancer cells home to it; mutated in a third of Waldenström patients and targeted by plerixafor for stem-cell mobilisation.","summary":"CXCR4 binds CXCL12 (SDF-1) to retain haematopoietic stem cells in the marrow niche and guides metastasis of solid tumours to bone. Plerixafor (2008) blocks it to mobilise stem cells for autologous transplant; motixafortide (2023) does the same in myeloma. WHIM-like CXCR4 mutations in ~30-40% of Waldenström macroglobulinaemia slow BTK-inhibitor response; mavorixafor is in trials. CXCR4 is also imaged with Ga-68 pentixafor and treated with Lu-177 pentixather in marginal zone lymphoma and myeloma (theranostic, experimental). Balixafortide and ulocuplumab failed in solid tumours.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/CXCR4","links":[{"label":"CXCR4 in WM (Blood 2014)","url":"https://doi.org/10.1182/blood-2014-01-550905"}],"tags":["gap-fill"],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CXCR4","hgnc":"HGNC:2561","ensembl":"ENSG00000121966","uniprot":"P61073","entrez":"7852","biology":"G-protein-coupled receptor; CXCL12 binding activates Gαi, PI3K/AKT and MAPK, promoting chemotaxis, survival and retention in stromal niches; truncating C-terminal mutations impair receptor internalisation (WHIM syndrome).","whereFound":["Waldenström macroglobulinaemia (30-40% mutation)","Myeloma, lymphoma, AML (expression)","Breast, prostate and other solid tumours (metastatic homing)"],"targetClass":"other","prevalence":[],"route":"/targets/cxcr4/"}
{"id":"dll3","kind":"target","name":"DLL3","aka":[],"tldr":"A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them.","summary":"Delta-like ligand 3 is an inhibitory Notch ligand aberrantly surface-expressed in ~85% of small-cell lung cancer and neuroendocrine prostate cancer. The first DLL3 ADC (rovalpituzumab tesirine) failed; the T-cell engager tarlatamab (Imdelltra) succeeded, with a survival benefit in second-line SCLC (DeLLphi-304). Trispecifics and CAR-T follow. For radiopharmaceuticals it is a target in waiting rather than in use: no DLL3 radioligand is in the clinic, and the nearest commitment is the discovery-stage DLL3 programme Telix acquired from ImaginAb in January 2025, which carries no candidate code or isotope. A surface antigen present on most small-cell lung cancers, in a disease where a scan-then-treat pair does not yet exist, is the obvious place for one.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DLL3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DLL3"}],"tags":["t-cell-engager-target"],"related":[],"indications":["sclc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["abdera-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"DLL3","hgnc":"HGNC:2909","ensembl":"ENSG00000090932","uniprot":"Q9NYJ7","entrez":"10683","biology":"Normally intracellular Golgi protein; ASCL1-driven neuroendocrine lineage exposes it on the membrane.","whereFound":["Small-cell lung cancer","Neuroendocrine prostate cancer","Large-cell neuroendocrine carcinoma"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"sclc","pct":"80-85","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/DLL3"},{"indicationId":"prostate","pct":"70-80","measure":"Neuroendocrine prostate cancer only","source":"https://en.wikipedia.org/wiki/DLL3","note":"Rare in adenocarcinoma"}],"route":"/targets/dll3/"}
{"id":"fap","kind":"target","name":"FAP","aka":[],"tldr":"FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.","summary":"Fibroblast activation protein is expressed on cancer-associated fibroblasts in >90% of epithelial cancers, with minimal expression in normal adult tissue. FAPI PET tracers (68Ga-FAPI-46, 18F-FAPI-74) offer high tumour-to-background contrast, including in cancers where FDG is weak (pancreatic, gastric, low-grade). FAP-targeted radioligands (177Lu/225Ac-FAP-2286) are in development.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha"}],"tags":["theranostic","pet-target","stroma"],"related":["f-18","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["ratio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FAP","hgnc":"HGNC:3590","ensembl":"ENSG00000078098","uniprot":"Q12884","entrez":"2191","biology":"Serine protease on activated fibroblasts; a stromal target rather than a tumour-cell target, so it is pan-cancer but does not report on the malignant cell itself.","whereFound":["Pancreatic","Gastric","Breast","Sarcoma","Almost all desmoplastic tumours"],"targetClass":"stroma","prevalence":[],"route":"/targets/fap/"}
{"id":"folr1","kind":"target","name":"Folate receptor alpha","aka":[],"tldr":"Folate receptor alpha is a vitamin receptor that ovarian cancer cells carry in large numbers, used as the docking site for the ADC mirvetuximab.","summary":"FRα is overexpressed in high-grade serous ovarian cancer, endometrial cancer, and lung adenocarcinoma. Mirvetuximab soravtansine (Elahere) is approved in FRα-high platinum-resistant ovarian cancer (MIRASOL). Next-generation FRα ADCs with topoisomerase-I payloads (ZW191, luveltamab tazevibulin, rinatabart sesutecan) target lower-expressing tumours.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Folate_receptor_1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Folate_receptor_1"}],"tags":["adc-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FOLR1","hgnc":"HGNC:3791","ensembl":"ENSG00000110195","uniprot":"P15328","entrez":"2348","biology":"GPI-anchored folate transporter; limited to apical surfaces in normal kidney, lung, and choroid plexus.","whereFound":["High-grade serous ovarian (~80% any expression)","Endometrial","NSCLC adenocarcinoma","TNBC (subset)"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/folr1/"}
{"id":"gpc3","kind":"target","name":"Glypican-3","aka":[],"tldr":"Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.","summary":"Glypican-3 is a heparan sulfate proteoglycan that modulates Wnt and Hedgehog signalling; it is a fetal liver protein expressed in 70-80% of hepatocellular carcinoma and essentially absent from normal adult liver, which gives cell and bispecific therapies a clean target. It is also found in hepatoblastoma and yolk-sac tumours. Antibodies failed as monotherapy (codrituzumab), suggesting that simply binding GPC3 is not enough. GPC3 CAR-T, including armoured constructs from AstraZeneca/Neogene and Chinese groups, and GPC3×CD3 bispecifics are showing responses, though durability and the hostile liver microenvironment remain concerns. The simple version is a liver-development protein that reappears in liver cancer, letting engineered immune cells recognise the tumour.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glypican_3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glypican_3"}],"tags":["car-t-target"],"related":[],"indications":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GPC3","hgnc":"HGNC:4451","ensembl":"ENSG00000147257","uniprot":"P51654","entrez":"2719","biology":"Glypican-3 is a heparan sulfate proteoglycan modulating Wnt and Hedgehog signalling.","whereFound":["Hepatocellular carcinoma","Hepatoblastoma","Yolk-sac tumours"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"hcc","pct":"70-80","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/Glypican_3"}],"route":"/targets/gpc3/"}
{"id":"grpr","kind":"target","name":"GRPR (gastrin-releasing peptide receptor)","aka":[],"tldr":"GRPR is a hormone receptor abundant in early and hormone-sensitive prostate cancer, imaged and treated with bombesin-like radioligands.","summary":"The gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor for bombesin and GRP whose expression is high in hormone-sensitive prostate cancer and falls with castration resistance. It is overexpressed in primary and hormone-naive prostate cancer, often in PSMA-negative tumours, as well as in ER-positive breast cancer and GIST, which makes it a complementary theranostic target to PSMA. Bombesin-like radioligands exploit it: 68Ga-RM2 PET for imaging and 177Lu-NeoB (Novartis) for therapy are in clinical trials. Because expression declines as disease becomes castration-resistant, GRPR agents may suit earlier disease or PSMA-negative patients rather than replacing PSMA therapy. A newcomer can think of GRPR as a second radioactive address on prostate cancer, useful where PSMA is dim.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Gastrin-releasing_peptide_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastrin-releasing_peptide_receptor"}],"tags":["theranostic"],"related":["ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GRPR","hgnc":"HGNC:4609","ensembl":"ENSG00000126010","uniprot":"P30550","entrez":"2925","biology":"G-protein-coupled receptor for bombesin/GRP; expression falls with castration resistance.","whereFound":["Hormone-sensitive prostate cancer","ER+ breast cancer","GIST"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"prostate","pct":100,"measure":"Receptor autoradiography, GRPR in 30 of 30 invasive prostate carcinomas","source":"https://pubmed.ncbi.nlm.nih.gov/10070977/","note":"Markwalder and Reubi 1999 (Cancer Res); receptor density was high in carcinoma and PIN and low or absent in normal and hyperplastic prostate"}],"route":"/targets/grpr/"}
{"id":"her2","kind":"target","name":"HER2","aka":[],"tldr":"A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.","summary":"Human epidermal growth factor receptor 2 is a receptor tyrosine kinase amplified in ~15-20% of breast cancers and a subset of gastric, colorectal, lung (mutations), and biliary cancers. Trastuzumab (1998) was the first targeted antibody in solid tumours. Trastuzumab deruxtecan redefined the target by working in 'HER2-low' tumours that older drugs ignored, and in 2026 gained approval in early-stage disease.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HER2/neu","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HER2/neu"}],"tags":["adc-target","driver"],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["precirix"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06369831"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB2","hgnc":"HGNC:3430","ensembl":"ENSG00000141736","uniprot":"P04626","entrez":"2064","biology":"Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.","whereFound":["HER2+ breast cancer (~15-20%)","HER2-low breast cancer (~50%)","Gastric/GEJ (~15-20%)","HER2-mutant NSCLC (~2-3%)","Colorectal (~3-5%)","Biliary tract"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"breast-her2-positive","pct":100,"measure":"IHC 3+ or ISH-amplified (defining)","source":"https://www.nature.com/articles/s41591-025-03981-4"}],"route":"/targets/her2/"}
{"id":"klk2","kind":"target","name":"KLK2 (kallikrein-2)","aka":[],"tldr":"A relative of PSA that stays attached to prostate cancer cells, used as a T-cell engager address by J&J.","summary":"Human kallikrein-2 (KLK2) is an androgen-regulated serine protease that activates PSA; unlike PSA it is retained on the prostate cell membrane, which makes it a usable address for cell-surface therapies. Expression is nearly universal in prostate cancer and prostate-restricted elsewhere, so a KLK2-directed drug can engage T cells against the tumour with little on-target damage to other tissues. The lead agent is Johnson & Johnson's pasritamig (JNJ-78278343, a KLK2 x CD3 bispecific), which showed low cytokine release and PSA responses in phase 1 and is in phase 3 (KLK2-P3-01) in metastatic castration-resistant prostate cancer. Open questions are whether KLK2 expression persists in neuroendocrine or AR-independent disease and how it compares with PSMA as an engager target. The plain version: KLK2 is a cousin of PSA that stays stuck to cancer cells, so drugs can grab it.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/KLK2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KLK2"}],"tags":["t-cell-engager-target"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: no peer-reviewed KLK2 expression series with a stated denominator was found for prostate cancer; 'nearly universal' rests on KLK2 being an androgen-regulated, prostate-restricted gene rather than on a published positivity rate."],"symbol":"KLK2","hgnc":"HGNC:6363","ensembl":"ENSG00000167751","uniprot":"P20151","entrez":"3817","biology":"Serine protease activating PSA; androgen-regulated.","whereFound":["Prostate cancer (nearly universal)"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/klk2/"}
{"id":"nectin4","kind":"target","name":"Nectin-4","aka":[],"tldr":"Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.","summary":"Nectin-4 is expressed at high levels in urothelial carcinoma and also in breast, lung, and pancreatic cancers. Enfortumab vedotin plus pembrolizumab is first-line standard in advanced urothelial cancer (EV-302). Next-generation Nectin-4 ADCs with topoisomerase-I payloads (MK-3120) and Nectin-4×TROP2 bispecific ADCs (AK146D1, AVZO-103) are in development.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Nectin-4","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nectin-4"}],"tags":["adc-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"NECTIN4","hgnc":"HGNC:19688","ensembl":"ENSG00000143217","uniprot":"Q96NY8","entrez":"81607","biology":"Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.","whereFound":["Urothelial carcinoma (>80%)","TNBC","NSCLC","Pancreatic"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/nectin4/"}
{"id":"parp","kind":"target","name":"PARP","aka":["PARP1/2","Poly [ADP-ribose] polymerase 2"],"tldr":"PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.","summary":"PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib) exploit synthetic lethality with BRCA1/2 mutations and homologous recombination deficiency in ovarian, breast, prostate, and pancreatic cancer. Olaparib is approved in adjuvant germline-BRCA breast cancer (OlympiA). PARP1-selective inhibitors (saruparib) and PARP PET tracers are the next step.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PARP_inhibitor"}],"tags":["synthetic-lethality"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PARP1","hgnc":"HGNC:270","ensembl":"ENSG00000143799","uniprot":"P09874","entrez":"142","biology":"Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.","whereFound":["BRCA/HRD ovarian, breast, prostate, pancreatic cancers"],"targetClass":"enzyme","prevalence":[{"indicationId":"prostate","pct":"20-25","measure":"HRR gene alteration (mCRPC)","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"BRCA2 ~8-10%"}],"route":"/targets/parp/"}
{"id":"psma","kind":"target","name":"PSMA","aka":[],"tldr":"A protein on prostate cancer cells that lets doctors both see the cancer on a PET scan and hit it with a radioactive drug.","summary":"Prostate-specific membrane antigen is the archetypal theranostic target. PSMA PET (Pylarify, Illuccix, Locametz, Pylarify TruVu) is standard for staging; 177Lu-PSMA-617 (Pluvicto) is approved before and after chemotherapy in metastatic castration-resistant prostate cancer. Alpha-emitting 225Ac-PSMA agents and PSMA-targeted bispecifics and CAR-T are in trials.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II"}],"tags":["theranostic","pet-target"],"related":["lu-177","ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["aaa817","jnj-87189401","hrs-4357","fpi-2265"],"companies":["artbio","convergent-therapeutics","point-biopharma"],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":[],"trials":["nct07567521","nct06383052","nct05381103","nct06906471","nct07258407"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FOLH1","hgnc":"HGNC:3788","ensembl":"ENSG00000086205","uniprot":"Q04609","entrez":"2346","biology":"PSMA is a type II transmembrane glutamate carboxypeptidase; expression increases with grade and castration resistance. Also expressed in tumour neovasculature of other cancers.","whereFound":["Prostate cancer (>90%)","Neovasculature of RCC, glioma, others"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"prostate","pct":">90","measure":"PSMA PET positivity, metastatic disease","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12796145/","note":"~10% PSMA-negative or low"},{"indicationId":"rcc","pct":"60-80","measure":"Neovascular PSMA expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12796145/","note":"Clear-cell; imaging studies"}],"route":"/targets/psma/"}
{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","aka":[],"tldr":"Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care.","summary":"Somatostatin receptor 2 is a G-protein-coupled receptor overexpressed on well-differentiated neuroendocrine tumours, which internalise bound somatostatin analogues and so can be both imaged and treated with the same peptide. 68Ga-DOTATATE PET (Netspot) and 177Lu-DOTATATE (Lutathera, NETTER-1 and NETTER-2) established the theranostic paradigm, in which a diagnostic scan selects patients for a matched radioligand. SSTR PET is positive in 80-90% of well-differentiated neuroendocrine tumours but lower in grade 3, and the receptor is also expressed in meningioma, 30-50% of small-cell lung cancer, and some breast cancers. Alpha-emitting 225Ac-DOTATATE (RYZ101) and 212Pb-DOTAMTATE are in phase 3, testing whether alpha particles outperform beta. The simple version is a hormone receptor that lets doctors see and treat neuroendocrine tumours with the same molecule.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2"}],"tags":["theranostic"],"related":["ga-68","lu-177","ac-225","pb-212"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["point-biopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SSTR2","hgnc":"HGNC:11331","ensembl":"ENSG00000180616","uniprot":"P30874","entrez":"6752","biology":"G-protein-coupled receptor; also expressed in meningioma, small-cell lung cancer, and some breast cancers.","whereFound":["Neuroendocrine tumours","Meningioma","Small-cell lung cancer (subset)"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"neuroendocrine","pct":"80-90","measure":"SSTR PET positivity (well-differentiated)","source":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2","note":"Lower in grade 3"},{"indicationId":"sclc","pct":"30-50","measure":"IHC/imaging","source":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2"}],"route":"/targets/sstr2/"}
{"id":"steap1","kind":"target","name":"STEAP1","aka":[],"tldr":"STEAP1 is a protein on the surface of most prostate cancer cells, now the address for a T-cell engager in phase 3.","summary":"Six-transmembrane epithelial antigen of the prostate 1 is expressed in most prostate cancers including PSMA-low and neuroendocrine-like disease, with limited normal expression. Xaluritamig (STEAP1×CD3 XmAb 2+1) produced PSA50 in ~half of heavily pretreated mCRPC patients at target doses in phase 1 and is in two phase 3 trials (XALute post-taxane; XALience with abiraterone chemo-naive). Also an ADC target historically (vandortuzumab vedotin, discontinued).","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/STEAP1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/STEAP1"}],"tags":["t-cell-engager-target"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: no peer-reviewed STEAP1 expression series with a stated denominator was found for prostate cancer; the widely repeated '>80%' figure could not be traced to a series with an n, so it has been removed."],"symbol":"STEAP1","hgnc":"HGNC:11378","ensembl":"ENSG00000164647","uniprot":"Q9UHE8","entrez":"26872","biology":"STEAP1 is a metalloreductase at cell junctions, upregulated by androgen receptor signalling; its expression is partly independent of PSMA, making it complementary.","whereFound":["Prostate cancer (most cases)","Ewing sarcoma","Bladder (subset)"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/steap1/"}
{"id":"trop2","kind":"target","name":"TROP2","aka":[],"tldr":"TROP2 is a surface glycoprotein present at high levels on most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) and at low levels on normal tissue. It does not drive the cancer; it is a delivery address, used by the approved ADCs sacituzumab govitecan and datopotamab deruxtecan and by sacituzumab tirumotecan, with a TROP2 PET tracer in development to pick patients.","summary":"Trophoblast cell-surface antigen 2 is a transmembrane glycoprotein overexpressed in most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) with low normal-tissue expression. It is not an oncogenic driver; it is a delivery address. Three TROP2 ADCs are approved or in registration (sacituzumab govitecan, datopotamab deruxtecan, sacituzumab tirumotecan) and a TROP2 PET tracer is in development to select patients.","asOf":"2026-09-04","links":[{"label":"UniProt P09758: TACSTD2 (TROP2)","url":"https://www.uniprot.org/uniprotkb/P09758/entry"}],"tags":["adc-target","pet-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TACSTD2","hgnc":"HGNC:11530","ensembl":"ENSG00000184292","uniprot":"P09758","entrez":"4070","biology":"Regulates calcium signalling and cell adhesion; overexpression correlates with poor prognosis. Expression is heterogeneous within tumours, which limits the value of IHC selection. Internalises on antibody binding and traffics to lysosomes, which is what makes it a good ADC target.","whereFound":["Triple-negative breast cancer (~80-90% express)","HR+ breast cancer","NSCLC","Urothelial carcinoma","Gastric, pancreatic, endometrial cancers"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/trop2/"}
{"id":"aaa817","kind":"drug","name":"AAA817","aka":["[225Ac]Ac-PSMA-617"],"tldr":"AAA817 is an experimental radioligand therapy from Novartis Pharmaceuticals in phase 3 trials for prostate cancer, aimed at PSMA.","summary":"AAA817 is a radioligand therapy developed by Novartis Pharmaceuticals. Its target is PSMA (the sponsor names PSMA). The sponsor states: Inside the body, AAA817 ([225Ac]Ac-PSMA-617) attaches to PSMA on the surface of prostate cancer cells and emits radiation to kill them; this treatment is also called a radioligand therapy. ClinicalTrials.gov describes the intervention as: AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits radiation to kill them. This treatment is also called a radioligand therapy. It is the investigational product in 2 recruiting or active industry-led phase 2 and phase 3 interventional cancer trials, including phase 3 studies NCT06855277 (Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC) and NCT06780670 (Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy), in prostate cancer. The largest, NCT06855277, plans to enrol 940 participants with primary completion expected 2028-09-29. Status reflects the highest phase registered on ClinicalTrials.gov; no efficacy results are recorded here.","status":"phase-3","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov: trials of AAA817","url":"https://clinicaltrials.gov/search?intr=AAA817"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177","ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06855277","nct06780670"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor pipeline pages)","editedOn":"2026-09-11"},"modality":"radioligand","mechanism":"Inside the body, AAA817 ([225Ac]Ac-PSMA-617) attaches to PSMA on the surface of prostate cancer cells and emits radiation to kill them; this treatment is also called a radioligand therapy.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/aaa817/"}
{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","aka":[],"tldr":"Abiraterone is a pill that shuts down testosterone production everywhere, including inside the tumour. Discovered at the Institute of Cancer Research, now generic and used from the first metastatic diagnosis.","summary":"Abiraterone acetate irreversibly inhibits CYP17A1 (17-alpha-hydroxylase and 17,20-lyase), shutting down androgen synthesis in the adrenal glands and inside the tumour, not just the testes; it is given with prednisone to offset mineralocorticoid excess. Its evidence spans advanced prostate cancer: COU-AA-301 and 302 (mCRPC post- and pre-docetaxel), LATITUDE and STAMPEDE (mHSPC, overall survival benefit; LATITUDE OS 53.3 versus 36.5 months, HR 0.66) and PEACE-1 (triplet with docetaxel). Generic since 2018 to 2019, it is the backbone partner for PARP inhibitors (PROpel, MAGNITUDE), capivasertib (CAPItello-281) and Pluvicto (PSMAddition). Open questions are how to choose between abiraterone and the AR antagonists, and which men need a third drug. Discovered at the Institute of Cancer Research, it is the affordable hormone pill most men with metastatic prostate cancer now start at diagnosis.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Abiraterone_acetate","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Abiraterone%20acetate"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc","prostate-mcrpc","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["johnson-johnson"],"institutions":["royal-marsden"],"pathways":[],"terms":[],"trials":["stampede","nct06520345","nct07611110"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Zytiga (generic)","modality":"Small-molecule CYP17A1 inhibitor","mechanism":"Irreversible CYP17A1 (17α-hydroxylase/17,20-lyase) inhibition blocks adrenal and intratumoural androgen synthesis.","approvals":[{"region":"US","year":2011,"indication":"mCRPC after docetaxel"},{"region":"US","year":2012,"indication":"mCRPC pre-chemotherapy"},{"region":"US","year":2018,"indication":"High-risk mHSPC (LATITUDE)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/abiraterone/"}
{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","aka":[],"tldr":"Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply.","summary":"Novartis (225Ac-PSMA-617, phase 3 AcTION), Bayer (225Ac-PSMA-Trillium with albumin binder, PAnTHA phase 1 at ASCO GU 2026), Fusion/AstraZeneca (FPI-2265, 225Ac-PSMA-I&T, phase 3 AlphaBreak), and academic 225Ac-PSMA data from South Africa and Germany. Xerostomia from salivary uptake is dose-limiting.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Actinium-225 PSMA agents","url":"https://clinicaltrials.gov/search?intr=225Ac-PSMA-617"}],"tags":[],"related":["ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["psma"],"drugs":[],"companies":["novartis","bayer","fusion-pharma","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07590934"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"225Ac-PSMA-617, 225Ac-PSMA-I&T, BAY 3563254 (Trillium)","modality":"Targeted alpha therapy","mechanism":"PSMA ligand with 225Ac; four alpha emissions per decay chain.","approvals":[],"mechanismSteps":["Radioligand circulates and binds PSMA on tumour cells","Ligand is internalised or retained at the membrane","Alpha (225Ac) emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV infusion","schedule":"Trial regimens ~100 kBq/kg every 6-8 weeks","monitoring":"Salivary gland toxicity (xerostomia), renal function, blood counts","source":"https://clinicaltrials.gov"},"toxicity":[{"event":"Xerostomia","note":"Dose-limiting in academic series"},{"event":"Anaemia"},{"event":"Thrombocytopenia"},{"event":"Renal toxicity"}],"access":[{"country":"US","reimbursement":"Investigational (phase 3)","asOf":"2026-09-06"},{"country":"DE","reimbursement":"Compassionate use at selected centres (Heidelberg and others)","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-06","type":"filing","region":"US","note":"AstraZeneca completes Fusion Pharmaceuticals acquisition; FPI-2265 phase 3 planned","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/ac225-psma/"}
{"id":"al2846","kind":"drug","name":"AL2846","aka":[],"tldr":"AL2846 is an experimental small-molecule drug from Chia Tai Tianqing Pharmaceutical in phase 3 trials for thyroid cancer, aimed at MET and RET.","summary":"AL2846 is a small-molecule drug developed by Chia Tai Tianqing Pharmaceutical. Its targets are MET, RET and KIT (the sponsor names c-MET, c-KIT, VEGFR1, RET). The sponsor states: A multi-target tyrosine kinase inhibitor capsule with significant inhibitory effects on c-MET, c-KIT, VEGFR1 and RET. ClinicalTrials.gov describes the intervention as: AL2846 Capsule is a multi - target tyrosine kinase inhibitor, which has significant inhibitory effects on c-Mesenchymal-epithelial transition factor (c - MET), stem cell factor receptor (c - KIT), VEGFR1 and Ret Proto-Oncogene (RET). It is the investigational product in 1 recruiting or active industry-led phase 2 and phase 3 interventional cancer trial, including the phase 3 study NCT06860971 (A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma), in thyroid cancer. The largest, NCT06860971, plans to enrol 144 participants with primary completion expected 2027-01. Status reflects the highest phase registered on ClinicalTrials.gov; no efficacy results are recorded here.","status":"phase-3","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov: trials of AL2846","url":"https://clinicaltrials.gov/search?intr=AL2846"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06860971"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor pipeline pages)","editedOn":"2026-09-11"},"modality":"small molecule (structure undisclosed or not yet in PubChem)","mechanism":"A multi-target tyrosine kinase inhibitor capsule with significant inhibitory effects on c-MET, c-KIT, VEGFR1 and RET.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/al2846/"}
{"id":"alphamedix","kind":"drug","name":"212Pb-DOTAMTATE","aka":[],"tldr":"An alpha-particle version of neuroendocrine radioligand therapy that produced responses in over half of patients who had never had PRRT, with FDA Breakthrough designation.","summary":"ALPHAMEDIX-02 (Sanofi/Orano Med/RadioMedix, October 2025): met all primary endpoints; ORR 54.3% in PRRT-naive patients with ~70-75% progression-free at about 3 years, and durable disease control in PRRT-exposed patients (~83% progression-free at 18 months). Breakthrough Therapy designation 2024. Sanofi acquired global rights (2024); registrational strategy under discussion. Supply relies on Orano Med's 212Pb generators.","status":"phase-2","asOf":"2026-09-07","links":[{"label":"Sanofi press release Oct 2025","url":"https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053"}],"tags":[],"related":["pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["prrt","targeted-alpha-therapy"],"targets":["sstr2"],"drugs":[],"companies":["orano-med","radiomedix"],"institutions":[],"pathways":[],"terms":[],"trials":["alphamedix-02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"AlphaMedix","modality":"Targeted alpha therapy (lead-212)","mechanism":"DOTAMTATE (SSTR2 agonist) chelating 212Pb, which decays via 212Bi to emit an alpha particle at the tumour cell.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/alphamedix/"}
{"id":"cabazitaxel","kind":"drug","name":"Cabazitaxel","aka":[],"tldr":"A second taxane that works after docetaxel and beat a second hormone pill head-to-head (CARD).","summary":"Cabazitaxel is a taxane with low affinity for the P-glycoprotein efflux pump, so it remains active in docetaxel-resistant disease. It is used in metastatic castration-resistant prostate cancer after docetaxel, with neutropenia as its main toxicity. TROPIC (2010) showed an overall survival benefit after docetaxel, and CARD (2019) showed it was superior to switching to a second androgen receptor pathway inhibitor in men who had already had one ARPI and docetaxel. It served as the comparator in TheraP, where it lost to 177Lu-PSMA-617 on PSA50 response (66% versus 37%) although overall survival was similar (HR 0.97), and in XALute against the T-cell engager xaluritamig. Its place relative to radioligands and T-cell engagers is therefore still being worked out. For a newcomer, it is the second taxane that works after docetaxel and beat a second hormone pill head-to-head.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Cabazitaxel","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Cabazitaxel"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["therap","nct07611110"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Jevtana","modality":"Cytotoxic chemotherapy (taxane)","mechanism":"Taxane with low P-glycoprotein affinity, active in docetaxel-resistant disease.","approvals":[{"region":"US","year":2010,"indication":"mCRPC after docetaxel"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/cabazitaxel/"}
{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","aka":[],"tldr":"A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.","summary":"CELESTIAL: OS 10.2 vs 8.0 months after sorafenib in HCC (HR 0.76). CheckMate 9ER: with nivolumab, first-line RCC. CABINET (2024-25): PFS 13.8 vs 4.4 months in pancreatic NETs and 8.4 vs 3.9 months in extra-pancreatic NETs after prior therapy, leading to FDA approval in March 2025; ESMO 2025 subgroup showed an 81% reduction in progression risk in lung and thymic NETs. COSMIC-312 (with atezolizumab, first-line HCC) improved PFS but not OS.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Cabozantinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Cabozantinib"}],"tags":[],"related":[],"indications":["hcc","rcc","neuroendocrine","thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cabinet","nct03690388"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In kidney cancer: CABOSUN (first line versus sunitinib, PFS benefit), METEOR (second line versus everolimus, OS 21.4 versus 16.5 months), CheckMate 9ER (with nivolumab, OS benefit), COSMIC-313 (triplet, no OS gain) and CONTACT-03 (no benefit from adding atezolizumab). The dose is 40 mg daily with nivolumab, and about 65 percent of patients have a grade 3 or higher event; the long half-life of about 99 hours matters when toxicity appears."],"brand":"Cabometyx","modality":"Small-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)","mechanism":"Oral inhibitor of MET, VEGFR2, AXL, RET, KIT and FLT3; MET/AXL inhibition counters anti-VEGF resistance.","approvals":[{"region":"US","year":2012,"indication":"Medullary thyroid cancer (Cometriq)"},{"region":"US","year":2016,"indication":"Advanced RCC"},{"region":"US","year":2019,"indication":"HCC previously treated with sorafenib"},{"region":"US","year":2025,"indication":"Advanced pancreatic and extra-pancreatic neuroendocrine tumours after prior therapy (CABINET)"},{"region":"US","year":2017,"indication":"First-line advanced RCC (CABOSUN)"},{"region":"US","year":2021,"indication":"First-line advanced RCC with nivolumab (CheckMate 9ER)"},{"region":"EU","year":2014,"indication":"Cometriq for medullary thyroid cancer; 21 Mar 2014. Cabometyx (RCC) Sep 2016"}],"mechanismSteps":["Blocks VEGFR2 on endothelium","Blocks MET and AXL, which tumours upregulate under hypoxia to escape anti-VEGF therapy","Reduces invasion and metastasis signalling"],"dosing":{"route":"Oral","schedule":"60 mg daily (Cabometyx tablets)","modifications":"40 mg then 20 mg for intolerance","monitoring":"Blood pressure, liver enzymes, wound healing"},"toxicity":[{"event":"Hand-foot skin reaction","anyGradePct":46,"grade3PlusPct":17,"note":"CELESTIAL"},{"event":"Hypertension","anyGradePct":29,"grade3PlusPct":16,"note":"CELESTIAL"},{"event":"Diarrhoea","anyGradePct":54,"grade3PlusPct":10,"note":"CELESTIAL"}],"access":[],"regulatoryEvents":[{"date":"2025-03-26","type":"approval","region":"US","note":"NET indication on CABINET","source":"https://www.ncf.net/post/2025-highlights-in-neuroendocrine-cancer"}],"route":"/drugs/cabozantinib/"}
{"id":"capecitabine","kind":"drug","name":"Capecitabine","aka":[],"tldr":"Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.","summary":"Capecitabine was approved by the FDA in 1998 for anthracycline- and taxane-resistant metastatic breast cancer and later for adjuvant stage III colon cancer (X-ACT: disease-free survival at least equivalent to bolus fluorouracil and leucovorin), metastatic colorectal cancer, perioperative chemoradiotherapy for rectal cancer and, with docetaxel, for anthracycline-pretreated breast cancer. The EU authorised Xeloda in 2001; it is also approved there for gastric cancer. It is the oral partner in CAPOX and CAPTEM and in the CREATE-X post-neoadjuvant breast regimen. Hand-foot syndrome, diarrhoea and cardiotoxicity are the key toxicities, and DPD deficiency (DPYD variants) causes severe or fatal toxicity, so genotype-guided dosing is increasingly used. Warfarin interaction carries a boxed warning.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Capecitabine","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=capecitabine"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/capecitabine"},{"label":"EPAR","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/xeloda"}],"tags":["nci-list","generic"],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06247995","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Xeloda","modality":"Oral fluoropyrimidine prodrug (antimetabolite)","mechanism":"Converted in three steps, the last by thymidine phosphorylase enriched in tumours, to fluorouracil; FdUMP blocks thymidylate synthase and FUTP is incorporated into RNA.","approvals":[{"region":"US","year":1998,"indication":"Metastatic breast cancer after anthracycline and taxane; later adjuvant and metastatic colorectal cancer, rectal chemoradiotherapy"},{"region":"EU","year":2001,"indication":"Colorectal, gastric and breast cancer"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/capecitabine/"}
{"id":"choline-c11","kind":"drug","name":"Choline C-11","aka":["[11C]choline"],"tldr":"Choline C-11 was the first PET tracer approved in the United States, in 2012, to find where prostate cancer has come back when PSA rises after treatment; PSMA tracers have now largely replaced it.","summary":"The FDA approved Choline C 11 Injection in September 2012, produced at the Mayo Clinic, for PET imaging of patients with suspected prostate cancer recurrence and non-informative bone scan, CT or MRI, the first approval of a PET agent for prostate cancer. Its 20-minute half-life means it must be made on site with a cyclotron, which confined it to a few centres. From 2020 the PSMA-targeted tracers gallium-68 PSMA-11 and piflufolastat F-18, with higher sensitivity at low PSA and longer half-lives, took over most recurrence imaging, and fluciclovine F-18 offered a distributable amino-acid alternative.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Choline_C-11","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Choline_C-11"},{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=choline%20c%2011"}],"tags":["gap-fill","chembl-universe"],"related":["f-18","ga-68","c-11"],"indications":["prostate"],"sections":[],"technologies":["pet","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Choline C 11 Injection","modality":"PET radiotracer, intravenous","mechanism":"Carbon-11-labelled choline is taken up by cells with high phosphatidylcholine synthesis, including prostate cancer, and imaged by PET within minutes because of the isotope's 20-minute half-life.","approvals":[{"region":"US","year":2012,"indication":"PET imaging of suspected prostate cancer recurrence with non-informative conventional imaging"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/choline-c11/"}
{"id":"dexrazoxane","kind":"drug","name":"Dexrazoxane","aka":["Cardioxane","Savene"],"tldr":"Dexrazoxane protects the heart from the cumulative damage of doxorubicin in women with metastatic breast cancer who need to keep receiving it, and, as Totect, limits tissue destruction when an anthracycline leaks out of a vein.","summary":"Dexrazoxane (Zinecard) was approved in May 1995 to reduce the incidence and severity of doxorubicin cardiomyopathy in women with metastatic breast cancer who have received a cumulative 300 mg/m2 and will continue doxorubicin, on randomised trials that markedly reduced cardiac events; it is not used from the start of treatment because of an early signal of reduced response, later not confirmed. Totect was approved in 2007 for anthracycline extravasation, given within six hours on three consecutive days, on two single-arm European studies in which surgery was avoided in the great majority. Dexrazoxane is also used in paediatric leukaemia and lymphoma protocols to protect against late cardiotoxicity, an area where long-term Children's Oncology Group follow-up has been reassuring about secondary malignancy. Myelosuppression adds to that of chemotherapy.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Dexrazoxane","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=dexrazoxane"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/dexrazoxanehydrochloride"}],"tags":["nci-list","supportive"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Zinecard / Totect","modality":"Cardioprotectant and extravasation antidote (bisdioxopiperazine)","mechanism":"Cyclic EDTA derivative hydrolysed intracellularly to a metal chelator that removes iron from anthracycline-iron complexes, limiting free-radical cardiac injury; also a catalytic topoisomerase II inhibitor, which underlies its action against extravasation injury.","approvals":[{"region":"US","year":1995,"indication":"Reduction of doxorubicin cardiomyopathy in women with metastatic breast cancer after 300 mg/m2 cumulative dose (Zinecard)"},{"region":"US","year":2007,"indication":"Anthracycline extravasation (Totect)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/dexrazoxane/"}
{"id":"docetaxel","kind":"drug","name":"Docetaxel","aka":[],"tldr":"The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.","summary":"Docetaxel is a taxane that stabilises microtubules and arrests dividing cells; in prostate cancer it also disrupts androgen receptor nuclear trafficking. It was the first chemotherapy to extend life in metastatic castration-resistant prostate cancer (TAX 327, 2004) and later moved to first metastatic diagnosis: CHAARTED (OS 57.6 versus 44.0 months, HR 0.61) and STAMPEDE showed an overall survival benefit in high-volume hormone-sensitive disease, and PEACE-1 and ARASENS built triplets by adding abiraterone or darolutamide. It is also widely used in breast, lung, gastric and head and neck cancers. Neutropenia, neuropathy and fluid retention limit its use in frail patients, and whether men with low-volume metastatic disease gain anything from it remains contested. For a newcomer, it is the workhorse chemotherapy given every three weeks across many cancers.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Docetaxel","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Docetaxel"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chaarted","stampede","nct06520345","nct07590934"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Taxotere (generic)","modality":"Cytotoxic chemotherapy (taxane)","mechanism":"Microtubule stabilisation; also disrupts AR nuclear trafficking.","approvals":[{"region":"US","year":1996,"indication":"Locally advanced or metastatic breast cancer after chemotherapy (Taxotere, NDA 020449)"},{"region":"US","year":2004,"indication":"Metastatic CRPC (with prednisone)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/docetaxel/"}
{"id":"donafenib","kind":"drug","name":"Donafenib","aka":[],"tldr":"Donafenib is a Chinese redesign of sorafenib that lived longer than the original in a head-to-head liver cancer trial and is approved in China as a first-line option.","summary":"Zelgen's donafenib was approved by the NMPA in June 2021 for first-line unresectable hepatocellular carcinoma on the ZGDH3 trial (668 patients: median overall survival 12.1 versus 10.3 months with sorafenib, hazard ratio 0.83; Journal of Clinical Oncology 2021), the first drug to beat sorafenib on survival in this setting. Radioiodine-refractory differentiated thyroid cancer followed in 2022. A modest gain, but a first for a Chinese company and a model of incremental chemistry (deuteration) turned into an approval.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Donafenib","links":[{"label":"Suzhou Zelgen Biopharmaceuticals","url":"https://www.zelgen.com/en/"},{"label":"ZGDH3 (J Clin Oncol 2021)","url":"https://doi.org/10.1200/JCO.20.02672"},{"label":"NMPA (National Medical Products Administration)","url":"https://www.nmpa.gov.cn"}],"tags":["china"],"related":[],"indications":["hcc","thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Zepsun","code":"CM4307","modality":"Small-molecule multi-kinase inhibitor (deuterated sorafenib)","mechanism":"Deuterium-substituted analogue of sorafenib inhibiting RAF kinases and VEGFR/PDGFR; deuteration slows metabolism and raises exposure.","approvals":[{"region":"China","year":2021,"indication":"First-line unresectable hepatocellular carcinoma (ZGDH3)"},{"region":"China","year":2022,"indication":"Radioiodine-refractory differentiated thyroid cancer"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/donafenib/"}
{"id":"durvalumab","kind":"drug","name":"Durvalumab","aka":[],"tldr":"A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.","summary":"PACIFIC (unresectable stage III NSCLC), ADRIATIC (limited-stage SCLC, 2024), TOPAZ-1 (biliary tract), HIMALAYA (HCC with tremelimumab), NIAGARA (perioperative muscle-invasive bladder cancer, 2025), MATTERHORN (perioperative gastric, 2025), and Q2 2026 high-risk non-muscle-invasive bladder cancer with BCG (POTOMAC). Partner of Dato-DXd in TROPION-Breast05.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Durvalumab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Durvalumab"}],"tags":[],"related":[],"indications":["sclc","hcc","hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05063565","nct06040099"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Imfinzi","modality":"Monoclonal antibody (anti-PD-L1)","mechanism":"Human IgG1 anti-PD-L1 with reduced Fc effector function.","approvals":[{"region":"US","year":2017,"indication":"Locally advanced or metastatic urothelial carcinoma after platinum (accelerated; indication withdrawn 2021)"},{"region":"US","year":2018,"indication":"Unresectable stage III NSCLC after chemoradiation"},{"region":"US","year":2026,"indication":"High-risk NMIBC with BCG"}],"mechanismSteps":["Antibody binds PD-L1","PD-1/PD-L1 engagement between T cell and tumour is blocked","Exhausted tumour-reactive T cells regain effector function","Interferon-γ and cytotoxic granules are released at the tumour","Tumour cells are killed; memory T cells persist"],"dosing":{"route":"IV infusion","schedule":"10 mg/kg every 2 weeks or 1,500 mg every 4 weeks (≥30 kg); up to 12 months after chemoradiation in stage III NSCLC","modifications":"Hold for grade 2 pneumonitis; discontinue for grade 3-4","monitoring":"Respiratory symptoms after chemoradiation, thyroid, LFTs, creatinine","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3"},"toxicity":[{"event":"Pneumonitis (any cause, PACIFIC)","anyGradePct":18.3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"vs 12.8% placebo; 1.1% fatal"},{"event":"Cough","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"},{"event":"Fatigue","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"},{"event":"Radiation pneumonitis","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"},{"event":"Upper respiratory infection","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"},{"event":"Dyspnoea","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"},{"event":"Rash","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3","note":"PACIFIC; all-grade ≥20%"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.astrazeneca-us.com/medicines/access-360","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended after chemoradiation in stage III NSCLC (TA798), biliary tract cancer, limited-stage SCLC, perioperative bladder and gastric cancer","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2017-05-01","type":"approval","region":"US","note":"Urothelial carcinoma (accelerated; later withdrawn 2021)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2018-02-16","type":"approval","region":"US","note":"Unresectable stage III NSCLC after chemoradiation (PACIFIC)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-03-27","type":"approval","region":"US","note":"Extensive-stage SCLC with chemotherapy (CASPIAN)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-09-02","type":"approval","region":"US","note":"Biliary tract cancer with chemotherapy (TOPAZ-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-10-21","type":"approval","region":"US","note":"HCC with tremelimumab (HIMALAYA)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-12-04","type":"approval","region":"US","note":"Limited-stage SCLC after chemoradiation (ADRIATIC)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-03-28","type":"approval","region":"US","note":"Perioperative muscle-invasive bladder cancer (NIAGARA)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-11","type":"approval","region":"US","note":"Perioperative gastric/GEJ cancer with FLOT (MATTERHORN)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-05-28","type":"approval","region":"US","note":"High-risk non-muscle-invasive bladder cancer with BCG (POTOMAC)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-combination-bacillus-calmette-guerin-high-risk-non-muscle-invasive-bladder"}],"route":"/drugs/durvalumab/"}
{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","aka":[],"tldr":"Enzalutamide is a second-generation androgen-receptor blocker that stops the receptor binding testosterone, entering the nucleus and switching on genes. It is approved at every stage of advanced prostate cancer, from rising PSA after surgery to castration-resistant disease, and fatigue, falls and memory problems are its main drawbacks.","summary":"Enzalutamide is a second-generation androgen receptor antagonist that blocks ligand binding, nuclear translocation and DNA binding, giving more complete AR blockade than older antiandrogens. It is approved across every stage of advanced prostate cancer: AFFIRM and PREVAIL (mCRPC), PROSPER (nmCRPC), ARCHES and ENZAMET (mHSPC, overall survival benefit; ARCHES OS HR 0.66) and EMBARK (high-risk biochemical recurrence, 2023, metastasis-free survival HR 0.42 with leuprolide). It is the partner in TALAPRO-2 (talazoparib) and the MEVPRO trials (mevrometostat), so the next generation of combinations is built on it. Fatigue, falls and cognitive effects are the main toxicities, which is why darolutamide or apalutamide is sometimes preferred in frail men. For a newcomer, enzalutamide is the most widely used androgen-receptor blocker, from rising PSA after surgery to late-stage disease.","status":"approved","asOf":"2026-09-27","wikipedia":"https://en.wikipedia.org/wiki/Enzalutamide","links":[{"label":"FDA supplement approval letter: Xtandi NDA 203415/S-026 and NDA 213674/S-016 (EMBARK overall survival), 24 July 2026","url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/203415Orig1s026;213674Orig1s016ltr.pdf"},{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Enzalutamide"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc","prostate-nmcrpc","prostate-mcrpc","prostate-bcr"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["mcrpc-mhspc"],"trials":["embark","nct06520345","nct07611110"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Xtandi","modality":"Small-molecule AR antagonist","mechanism":"Second-generation AR antagonist blocking ligand binding, nuclear translocation, and DNA binding.","approvals":[{"region":"US","year":2012,"indication":"mCRPC after docetaxel (pre-chemo 2014)"},{"region":"US","year":2018,"indication":"Non-metastatic CRPC"},{"region":"US","year":2019,"indication":"mHSPC (ARCHES)"},{"region":"US","year":2023,"indication":"High-risk biochemical recurrence (EMBARK)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2026-07-24","type":"label-change","region":"US","note":"US Prescribing Information updated with overall survival data from EMBARK (NDA 203415/S-026, NDA 213674/S-016; efficacy labelling change with clinical data)","source":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/203415Orig1s026;213674Orig1s016ltr.pdf"}],"route":"/drugs/enzalutamide/"}
{"id":"everolimus","kind":"drug","name":"Everolimus","aka":[],"tldr":"An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.","summary":"Everolimus is a rapalog that binds FKBP12 and allosterically inhibits mTORC1, a growth-signalling hub downstream of PI3K and AKT. It is approved in HR-positive breast cancer with exemestane after non-steroidal aromatase inhibitor failure, in progressive pancreatic, lung and GI neuroendocrine tumours, and in advanced RCC after sunitinib or sorafenib. BOLERO-2 showed PFS of 7.8 versus 3.2 months for everolimus plus exemestane versus exemestane alone, with no OS benefit; RADIANT-3 and RADIANT-4 showed PFS of 11.0 versus 4.6 and 3.9 months in NETs. Stomatitis (mitigated by dexamethasone mouthwash, SWISH), pneumonitis and hyperglycaemia are the main toxicities. evERA (2025) revived it as the partner of giredestrant after CDK4/6 inhibitors; it is the comparator beaten in LITESPARK-005 and COMPETE. For a newcomer, it is a growth-pathway pill with several niches rather than one dominant use.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Everolimus","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Everolimus"}],"tags":[],"related":[],"indications":["rcc","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04919226","radiant-3-4","compete"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In neuroendocrine tumours: RADIANT-3 (2011) gave PFS 11.0 versus 4.6 months in pancreatic NETs and RADIANT-4 (2016) PFS 11.0 versus 3.9 months in lung and GI NETs; it is now the comparator that 177Lu-edotreotide beat in COMPETE. In RADIANT-3 stomatitis affected 64 percent (7 percent grade 3 or higher), rash 49 percent and pneumonitis 17 percent; dexamethasone mouthwash (SWISH) prevents most stomatitis.","In kidney cancer: RECORD-1 (2008) gave PFS 4.9 versus 1.9 months against placebo after a VEGF-TKI, making everolimus the second-line standard from 2009; it has since been beaten by nivolumab (CheckMate 025), cabozantinib (METEOR), lenvatinib plus everolimus (Study 205) and belzutifan (LITESPARK-005), and is now mostly a comparator arm and a partner for lenvatinib at 5 mg daily. Feedback activation of AKT limits its cytostatic effect."],"brand":"Afinitor","modality":"Small-molecule mTOR inhibitor","mechanism":"Allosteric mTORC1 inhibitor (rapalog) via FKBP12.","approvals":[{"region":"US","year":2012,"indication":"HR+/HER2- advanced breast cancer with exemestane after NSAI failure"},{"region":"US","year":2011,"indication":"Progressive pancreatic NETs"},{"region":"US","year":2016,"indication":"Progressive non-functional lung and GI NETs"},{"region":"US","year":2009,"indication":"Advanced RCC after sunitinib or sorafenib"}],"mechanismSteps":[],"dosing":{"route":"Oral","schedule":"10 mg once daily","modifications":"5 mg for stomatitis or pneumonitis","monitoring":"Glucose, lipids, pneumonitis symptoms; steroid mouthwash prophylaxis"},"toxicity":[{"event":"Stomatitis","anyGradePct":59,"grade3PlusPct":8},{"event":"Pneumonitis","anyGradePct":16,"grade3PlusPct":3},{"event":"Hyperglycaemia","anyGradePct":14,"grade3PlusPct":5}],"access":[],"regulatoryEvents":[],"route":"/drugs/everolimus/"}
{"id":"fap-2286","kind":"drug","name":"FAP-2286 (177Lu / 68Ga)","aka":[],"tldr":"A FAP-targeted theranostic pair: one version images almost any solid tumour, the other treats it with radiation.","summary":"FAP-2286 is a theranostic pair: a cyclic peptide that binds fibroblast activation protein (FAP), linked to a DOTA chelator carrying 68Ga for PET imaging or 177Lu for beta therapy. FAP sits on cancer-associated fibroblasts in the stroma of most solid tumours rather than on cancer cells, so one agent can image and irradiate many tumour types, and the cyclic peptide gives longer tumour retention than the FAPI small molecules used for imaging. Clovis Oncology developed it until its 2022 bankruptcy; Novartis then acquired it via 3B Pharmaceuticals. The 177Lu-FAP-2286 LuMIERE phase 1/2 trial is dose-escalating in cycles every 6 weeks with pancreatic, sarcoma and breast cohorts. For a newcomer: a radioligand aimed at the scaffolding around tumours rather than the tumour cells.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of FAP-2286 (177Lu / 68Ga)","url":"https://clinicaltrials.gov/search?intr=FAP-2286"}],"tags":[],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":["fapi-pet","radioligand-therapy"],"targets":["fap"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05939414","nct06520345","nct07219238","nct05413850","nct06894511","nct05142696","nct04939610"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"FAP-2286","modality":"Theranostic pair (peptide radioligand)","mechanism":"Cyclic peptide FAP binder with DOTA chelator for 68Ga (imaging) or 177Lu (therapy).","approvals":[],"mechanismSteps":["Radioligand circulates and binds FAP on cancer-associated fibroblasts on tumour cells","Ligand is internalised or retained at the membrane","Beta emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV infusion (177Lu) or injection (68Ga)","schedule":"LuMIERE phase 1/2 dose escalation, cycles every 6 weeks","monitoring":"Blood counts, renal function","source":"https://clinicaltrials.gov/study/NCT04939610"},"toxicity":[{"event":"Anaemia"},{"event":"Thrombocytopenia"},{"event":"Fatigue"},{"event":"Nausea"}],"access":[{"country":"US","reimbursement":"Investigational","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2023-01","type":"filing","region":"US","note":"Novartis acquires rights after Clovis bankruptcy","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/fap-2286/"}
{"id":"florastamin-f18","kind":"drug","name":"Florastamin F-18","aka":["18F-florastamin","ProstaView","Prostaview Injection","florastamine","flortastamine F-18"],"tldr":"Florastamin is FutureChem's fluorine-18 PSMA PET tracer, and the first prostate cancer diagnostic developed in South Korea to be approved there — Korea's 43rd domestically developed new drug.","summary":"FutureChem, a Seoul radiopharmaceutical company, developed florastamin (FC303) as a fluorine-18 PSMA ligand for PET imaging of prostate cancer. Korea's Ministry of Food and Drug Safety approved it on 30 April 2026 as ProstaView injection, the country's 43rd domestically developed new drug and its first home-grown prostate cancer diagnostic; first commercial sales followed on 20 August 2026, the four-month gap being the reimbursement notice and hospital code registration every new Korean drug waits through. The company romanises the brand as both ProstaView and Prostaview and the ingredient appears as florastamin, florastamine and, in one wire report, flortastamine.\n\nThe registrational evidence is a domestic phase 3 trial at 11 institutions in men whose conventional imaging suggested recurrence or metastasis. Positive predictive value, the primary endpoint, was 86.96 per cent with a 95 per cent confidence interval lower bound of 79.01, against a pre-specified benchmark of 60.6; the CT, MRI and bone scans those same patients had already had returned about 60.16 per cent. A separate prospective study in 59 men with suspected intermediate-risk disease (Clinical Nuclear Medicine, 2025) put sensitivity at 72.4 per cent and specificity at 83.3 per cent against biopsy, with multiparametric MRI more sensitive at 89.7 per cent but less specific at 66.7 per cent and the same overall accuracy of 78 per cent — a fair description of what PSMA PET adds to MRI rather than replaces.\n\nRegistered phase 3 trials also cover initial staging of high-risk prostate cancer, the setting where gallium-68 PSMA-11 and piflufolastat are already approved in the United States and Europe. The approval matters beyond Korea because it is the diagnostic half of a domestic theranostic pair: FutureChem's lutetium-177 therapy FC705 (ludotadipep) targets the same antigen and is in phase 3 in Korea, so the approved tracer is the selection tool that therapy will be filed with.","status":"approved","asOf":"2026-09-22","links":[{"label":"FutureChem wins approval for Korea's first prostate cancer diagnostic (Seoul Economic Daily, English)","url":"https://en.sedaily.com/finance/2026/05/04/futurechem-wins-approval-for-koreas-first-prostate-cancer"},{"label":"First sales, with the 30 April 2026 approval date (Edaily, English)","url":"https://en.edaily.co.kr/news/eda202608205175/"},{"label":"Diagnostic accuracy of 18F-florastamin PET/CT in intermediate-risk suspected prostate cancer (Clin Nucl Med, 2025)","url":"https://doi.org/10.1097/RLU.0000000000005798"},{"label":"18F-florastamin PET/CT in men with clinical suspicion of prostate cancer (Prostate International, 2025)","url":"https://doi.org/10.1016/j.prnil.2025.07.001"},{"label":"ClinicalTrials.gov: trials of Florastamin F-18","url":"https://clinicaltrials.gov/search?intr=FC303"}],"tags":["diagnostic","psma","korea","ctgov-ingest"],"related":["ksnm","nuclear-medicine-and-molecular-imaging","f-18","prostate-bcr","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","pet"],"targets":["psma"],"drugs":[],"companies":["futurechem"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05936658","nct05004285","nct06754085"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2, curated); Korean approval read from the company's announcement in the English editions of Seoul Economic Daily and Edaily","editedOn":"2026-09-22"},"brand":"ProstaView","code":"FC303","modality":"PSMA-targeted PET radiotracer, fluorine-18","mechanism":"A fluorine-18-labelled ligand of prostate-specific membrane antigen that lights up prostate cancer on PET wherever it has spread.","approvals":[{"region":"South Korea","year":2026,"indication":"PET imaging of PSMA-positive lesions in men with prostate cancer whose existing imaging suggests recurrence or metastasis","note":"MFDS marketing approval 30 April 2026; Korea's 43rd domestically developed new drug"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2026-04-30","type":"approval","region":"South Korea","note":"MFDS marketing approval as Korea's 43rd domestically developed new drug","source":"https://en.sedaily.com/finance/2026/05/04/futurechem-wins-approval-for-koreas-first-prostate-cancer"}],"route":"/drugs/florastamin-f18/"}
{"id":"flotufolastat","kind":"drug","name":"Flotufolastat F-18","aka":[],"tldr":"Flotufolastat is a third PSMA PET tracer, with a radiohybrid chemistry designed to be reused for therapy.","summary":"Flotufolastat F-18 (Posluma) is a radiohybrid PSMA ligand: a silicon-fluoride acceptor allows 18F labelling for PET while the same scaffold can carry 177Lu for therapy, so imaging and treatment agents share one chemistry. It is used for PSMA PET in men with prostate cancer at initial staging and at biochemical recurrence. The LIGHTHOUSE (initial staging) and SPOTLIGHT (biochemical recurrence) trials supported approval in May 2023. Low urinary excretion aids reading of the pelvis, where bladder activity can obscure local recurrence with other tracers. It is the third PSMA PET tracer in the US after gallium-68 PSMA-11 and Pylarify, and head-to-head comparisons are limited. For a newcomer, it is a PSMA scan agent designed from the start to be reused for therapy.","status":"approved","asOf":"2026-09-06","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Flotufolastat%20F-18"}],"tags":[],"related":["f-18","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":[],"companies":["blue-earth-diagnostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Posluma","code":"18F-rhPSMA-7.3","modality":"PET imaging agent","mechanism":"Radiohybrid PSMA ligand; silicon-fluoride acceptor allows 18F imaging and 177Lu therapy on the same scaffold.","approvals":[{"region":"US","year":2023,"indication":"PSMA PET in prostate cancer"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/flotufolastat/"}
{"id":"fluciclovine-f18","kind":"drug","name":"Fluciclovine F-18","aka":[],"tldr":"Fluciclovine F-18 was the first PET tracer approved for finding recurrent prostate cancer after treatment (2016), and has been largely superseded since 2020 by PSMA PET.","summary":"Approved May 2016 for suspected recurrence with rising PSA; detection ~68% overall, lower at low PSA. EMSPOT/EMPIRE-1 (Lancet 2021) showed fluciclovine-guided salvage radiotherapy improved failure-free survival. PSMA PET (Ga-68 PSMA-11, piflufolastat, flotufolastat) has higher detection and displaced it.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Fluciclovine_(18F)","links":[{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Axumin"}],"tags":["gap-fill","diagnostic"],"related":["f-18","ga-68"],"indications":["prostate","glioblastoma"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":["blue-earth-diagnostics"],"institutions":[],"pathways":[],"terms":["biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Axumin","modality":"PET radiotracer (synthetic amino acid)","mechanism":"18F-labelled leucine analogue taken up via LAT1/ASCT2 amino-acid transporters upregulated in prostate cancer; low urinary excretion improves pelvic imaging.","approvals":[{"region":"US","year":2016,"indication":"PET imaging in men with suspected prostate cancer recurrence based on elevated PSA"},{"region":"EU","year":2017,"indication":"Same"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/fluciclovine-f18/"}
{"id":"fludeoxyglucose-f18","kind":"drug","name":"Fludeoxyglucose F-18 (FDG)","aka":[],"tldr":"The radioactive sugar used in almost every cancer PET scan, approved in the 1990s and made fresh each day by regional cyclotrons.","summary":"Fludeoxyglucose F-18 was the first PET radiopharmaceutical approved by the FDA (1994, initially for epilepsy foci and cardiac viability) and gained its oncology indication in 2000 for assessing abnormal glucose metabolism to assist in evaluating malignancy in patients with known or suspected cancer. It is produced under multiple abbreviated NDAs by commercial and academic cyclotron networks (PETNET, Cardinal Health, SOFIE, hospital sites) and is the tracer behind staging, response assessment (Deauville in lymphoma, PERCIST) and surveillance across most solid tumours. Its weaknesses, uptake in inflammation and poor sensitivity for indolent or low-glucose tumours, drive the development of target-specific tracers.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Fludeoxyglucose_(18F)","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Fludeoxyglucose%20F%2018"}],"tags":["test"],"related":["f-18"],"indications":["nsclc"],"sections":[],"technologies":["fdg-pet","pet-ct","pet"],"targets":[],"drugs":[],"companies":["petnet-solutions","cardinal-health","sofie-biosciences"],"institutions":[],"pathways":[],"terms":["suv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What a result means: 'hot spots' show tissue burning glucose fast; in a person with cancer they usually mark tumour, but infection, healing and brown fat can light up too, so findings are interpreted with CT and biopsy."],"brand":"FDG (multiple manufacturers)","modality":"PET imaging agent (glucose analogue)","mechanism":"18F-labelled glucose analogue taken up through GLUT transporters and trapped after phosphorylation by hexokinase, so metabolically active tumours accumulate signal.","approvals":[{"region":"US","year":1994,"indication":"First FDG NDA (neurology and cardiology indications)"},{"region":"US","year":2000,"indication":"Oncology: assessment of abnormal glucose metabolism to assist in evaluating malignancy"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/fludeoxyglucose-f18/"}
{"id":"fluoroestradiol-f18","kind":"drug","name":"Fluoroestradiol F-18 (FES PET)","aka":[],"tldr":"A PET scan that shows which breast cancer deposits still have oestrogen receptors, helping decide whether hormone therapy will work when biopsy is impractical.","summary":"Fluoroestradiol F-18 is a PET radiotracer in which 18F-labelled oestradiol binds oestrogen receptor alpha, imaging ER expression across every lesion in the body in a single non-invasive scan. It was approved in the US in May 2020 as an adjunct to biopsy for detecting ER-positive lesions in recurrent or metastatic breast cancer, and entered NCCN guidelines in 2024. It is used when biopsy is impractical or when lesions may have lost ER, because it predicts endocrine responsiveness and reveals heterogeneous receptor loss that a single biopsy would miss. It also serves as a pharmacodynamic tool in trials of ER degraders, measuring receptor occupancy, and is under study in ER-positive ovarian and endometrial cancers. Uptake in the liver limits assessment of hepatic metastases. FES PET tells the oncologist whether hormone therapy still has a target.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Fluoroestradiol_F-18","links":[{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Cerianna"}],"tags":["gap-fill","diagnostic"],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Cerianna","modality":"PET radiotracer (oestrogen receptor ligand)","mechanism":"18F-labelled oestradiol binds oestrogen receptor alpha, imaging ER expression across all lesions non-invasively.","approvals":[{"region":"US","year":2020,"indication":"Detection of ER-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/fluoroestradiol-f18/"}
{"id":"fpi-2265","kind":"drug","name":"FPI-2265","aka":["Ac225-PSMA I&T"],"tldr":"FPI-2265 is an experimental radioligand therapy from Fusion Pharmaceuticals in phase 2 trials for prostate cancer, aimed at PSMA.","summary":"FPI-2265 is a radioligand therapy developed by Fusion Pharmaceuticals. Its target is PSMA (the sponsor names PSMA). The sponsor states: A PSMA-targeting ligand (PSMA-I&T) radiolabeled with the alpha-emitter actinium-225, delivering targeted alpha radiotherapy to PSMA-positive prostate cancer cells. ClinicalTrials.gov describes the intervention as: Small molecule capable of binding to the domain of PSMA radiolabeled with Ac225. It is the investigational product in 3 recruiting or active industry-led phase 2 and phase 3 interventional cancer trials, in prostate cancer. The largest, NCT05219500, plans to enrol 115 participants with primary completion was scheduled for 2025-05-30 on the registry. Status reflects the highest phase registered on ClinicalTrials.gov; no efficacy results are recorded here.","status":"phase-2","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov: trials of FPI-2265","url":"https://clinicaltrials.gov/search?intr=FPI-2265"}],"tags":["pipeline","ctgov-ingest"],"related":["ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07611110","nct05219500","nct07590934","nct06909825"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor pipeline pages)","editedOn":"2026-09-11"},"modality":"radioligand","mechanism":"A PSMA-targeting ligand (PSMA-I&T) radiolabeled with the alpha-emitter actinium-225, delivering targeted alpha radiotherapy to PSMA-positive prostate cancer cells.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/fpi-2265/"}
{"id":"ga68-dotatate","kind":"drug","name":"Gallium-68 DOTATATE (and Cu-64 DOTATATE)","aka":[],"tldr":"The PET scan for neuroendocrine tumours that finds far more disease than older scans and confirms eligibility for lutetium radioligand therapy (the theranostic pair).","summary":"Ga-68 DOTATATE (Netspot, kit) approved June 2016; Cu-64 DOTATATE (Detectnet, 12.7-hour half-life allows central production) approved September 2020; Ga-68 DOTATOC (2019, academic). Changes management in about a third of patients; required before Lu-177 DOTATATE (Lutathera). Also images meningioma and paraganglioma.","status":"approved","asOf":"2026-09-08","links":[{"label":"Label: Netspot (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Netspot"},{"label":"Label: Detectnet (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Detectnet"}],"tags":["gap-fill","diagnostic"],"related":["ga-68","cu-64","lu-177"],"indications":["neuroendocrine","small-intestinal-net","pancreatic-net","lung-net"],"sections":[],"technologies":["sstr-pet","pet-ct","prrt","radioligand-therapy"],"targets":["sstr2"],"drugs":[],"companies":["novartis","curium"],"institutions":[],"pathways":[],"terms":["theranostics","prrt-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Netspot / Detectnet","modality":"PET radiotracer (somatostatin receptor ligand)","mechanism":"Radiolabelled somatostatin analogue binding SSTR2 on neuroendocrine tumours; PET replaces the older In-111 octreotide SPECT with higher sensitivity and same-day imaging.","approvals":[{"region":"US","year":2016,"indication":"PET localisation of SSTR-positive neuroendocrine tumours (Ga-68 DOTATATE)"},{"region":"US","year":2020,"indication":"Same (Cu-64 DOTATATE)"},{"region":"EU","year":2017,"indication":"SomaKit TOC (Ga-68 DOTATOC)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ga68-dotatate/"}
{"id":"ga68-psma-11","kind":"drug","name":"Gallium-68 gozetotide (PSMA-11)","aka":[],"tldr":"Gallium-68 PSMA-11 was the first PSMA PET tracer approved in the US (2020), and is made on site from a generator or cyclotron.","summary":"Gallium-68 gozetotide (PSMA-11) is a 68Ga-labelled urea-based ligand that binds prostate-specific membrane antigen, lighting up prostate cancer on PET wherever it has spread. It is made on site from a germanium-68 generator or cyclotron and used for initial staging of higher-risk disease, for biochemical recurrence, and to confirm PSMA expression before 177Lu-PSMA-617 therapy. The UCLA/UCSF academic NDA (2020) established PSMA PET in the US, followed by Telix's Illuccix kit (2021) and Gozellix (2025, longer shelf-life) and Novartis' Locametz (2022, companion for Pluvicto). It competes with 18F agents (Pylarify, Posluma) that offer central distribution and a longer half-life. Whether findings on PSMA PET should change treatment in the absence of outcome trials remains debated. In plain terms, it was the first PSMA PET tracer approved in the US.","status":"approved","asOf":"2026-09-27","links":[{"label":"Drugs@FDA: ANDA 216410, gallium Ga 68 gozetotide (RadioMedix)","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=216410"},{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Gallium-68%20gozetotide"}],"tags":[],"related":["f-18","ga-68","ge-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":[],"companies":["telix","novartis","radiomedix"],"institutions":["ucla-jonsson","ucsf"],"pathways":[],"terms":[],"trials":["nct07052214"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Illuccix / Gozellix / Locametz","modality":"PET imaging agent","mechanism":"68Ga-labelled urea-based PSMA ligand.","approvals":[{"region":"US","year":2020,"indication":"PSMA PET (UCLA/UCSF NDA); kits 2021-2022"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2026-06-08","type":"approval","region":"US","note":"Gallium Ga 68 gozetotide from RadioMedix approved under an abbreviated new drug application, ANDA 216410 (original approval)","source":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=216410"}],"route":"/drugs/ga68-psma-11/"}
{"id":"girentuximab-zr89","kind":"drug","name":"Zirconium-89 girentuximab","aka":["89Zr-DFO-girentuximab","Zircaix"],"tldr":"Zirconium-89 girentuximab is Telix's PET scan that tells whether a kidney mass is clear cell renal cell carcinoma without a biopsy; the phase 3 ZIRCON trial met its endpoints in 2023 and the product is under regulatory review.","summary":"Telix Pharmaceuticals' TLX250-CDx labels the anti-CAIX antibody girentuximab with zirconium-89. In the ZIRCON phase 3 trial of 300 patients with indeterminate renal masses, the scan identified clear cell renal cell carcinoma with high sensitivity and specificity against surgical histology. Telix filed with the FDA, which issued a refusal-to-file letter in 2024 over manufacturing information, and a resubmission followed. A further phase 3 trial is registered.","status":"phase-3","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov: trials of Zirconium-89 girentuximab","url":"https://clinicaltrials.gov/search?intr=TLX250-CDx"}],"tags":["pipeline","ctgov-ingest"],"related":["zr-89"],"indications":["rcc"],"sections":[],"technologies":["immuno-pet","pet"],"targets":[],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06750419"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2, curated)","editedOn":"2026-09-16"},"code":"TLX250-CDx","modality":"PET imaging antibody labelled with zirconium-89","mechanism":"Girentuximab binds carbonic anhydrase IX, expressed by nearly all clear cell renal cell carcinomas but not by normal kidney; the zirconium-89 label shows the tumour on PET days after injection.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/girentuximab-zr89/"}
{"id":"hrs-4357","kind":"drug","name":"HRS-4357","aka":[],"tldr":"HRS-4357 is an experimental investigational agent whose form is not stated in the registry from Jiangsu HengRui Medicine in phase 3 trials for prostate cancer, aimed at PSMA.","summary":"HRS-4357 is an investigational agent whose form is not stated in the registry developed by Jiangsu HengRui Medicine. Its target is PSMA (the sponsor names PSMA (inferred from trial population)). ClinicalTrials.gov describes the intervention as: HRS-4357 injection are administered each time, with dosing for 4 to 6 cycles. It is the investigational product in 1 recruiting or active industry-led phase 2 and phase 3 interventional cancer trial, including the phase 3 study NCT07311694 (A Phase III Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer), in prostate cancer. The largest, NCT07311694, plans to enrol 370 participants with primary completion expected 2027-12. Status reflects the highest phase registered on ClinicalTrials.gov; no efficacy results are recorded here.","status":"phase-3","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov: trials of HRS-4357","url":"https://clinicaltrials.gov/search?intr=HRS-4357"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07311694"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor pipeline pages)","editedOn":"2026-09-11"},"modality":"not stated (registered as a drug or biological on ClinicalTrials.gov)","mechanism":"Investigational agent whose form is not stated in the registry directed at PSMA, as stated in the ClinicalTrials.gov intervention record; the detailed mechanism is not stated.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/hrs-4357/"}
{"id":"i131-mibg","kind":"drug","name":"131I-MIBG (iobenguane I-131) therapy","aka":[],"tldr":"High-dose radioactive MIBG delivers radiation from inside neuroblastoma cells that take up noradrenaline; used for relapsed disease and tested in upfront therapy.","summary":"Response rate ~30-40% in relapsed/refractory MIBG-avid neuroblastoma (NANT, COG studies), with myelosuppression requiring stem-cell support at ≥12 mCi/kg. COG ANBL1531 randomised 131I-MIBG added to induction (primary results pending 2026). Commercial Azedra (for pheochromocytoma) was discontinued in 2024, leaving compounding and academic supply.","status":"established","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Iobenguane","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iobenguane"}],"tags":[],"related":["i-131"],"indications":["neuroblastoma","neuroblastoma-high-risk","metastatic-ppgl"],"sections":[],"technologies":["mibg-theranostics","radioligand-therapy"],"targets":[],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":["anbl1531"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"Radioligand therapy (beta, norepinephrine transporter)","mechanism":"Norepinephrine transporter uptake of radio-iodinated benzylguanidine; 131I beta emission (2 mm range).","approvals":[],"mechanismSteps":[],"dosing":{"route":"IV","schedule":"12-18 mCi/kg single or tandem doses with autologous stem-cell support; thyroid blockade with potassium iodide","monitoring":"Radiation isolation, counts, thyroid function, secondary malignancy"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/i131-mibg/"}
{"id":"ibritumomab-tiuxetan","kind":"drug","name":"Ibritumomab tiuxetan","aka":["Y-90 ibritumomab","Zevalin therapeutic regimen"],"tldr":"Zevalin is an antibody carrying a radioactive isotope that seeks out CD20 on lymphoma cells. It treats follicular lymphoma that has relapsed and is given as a one-off consolidation after chemotherapy.","summary":"Ibritumomab tiuxetan was the first radioimmunotherapy approved by the FDA, in February 2002, for relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin lymphoma including rituximab-refractory disease (Study 106-06: response in a majority of 54 rituximab-refractory patients), and in 2009 for consolidation after first-line chemotherapy in follicular lymphoma with a response (FIT trial: prolonged progression-free survival). The EU authorised Zevalin in 2004. Despite efficacy and a single-day treatment, use collapsed because of logistics between nuclear medicine and haematology, prolonged cytopenias and competition from rituximab maintenance and later agents; tositumomab (Bexxar) was discontinued in 2014. Severe cytopenias and infusion reactions carry boxed warnings.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Ibritumomab_tiuxetan","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ibritumomab%20tiuxetan"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/ibritumomabtiuxetan"},{"label":"EPAR","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/zevalin"}],"tags":["nci-list"],"related":["rituximab","y-90"],"indications":["follicular-lymphoma"],"sections":[],"technologies":["radioimmunotherapy"],"targets":["cd20"],"drugs":[],"companies":["acrotech-biopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Zevalin","modality":"Radioimmunotherapy (yttrium-90 labelled anti-CD20 antibody)","mechanism":"Murine anti-CD20 IgG1 (the parent of rituximab) chelated via tiuxetan to yttrium-90; beta emission delivers radiation to CD20-positive B cells and neighbouring tumour cells (crossfire), given after rituximab to clear circulating B cells.","approvals":[{"region":"US","year":2002,"indication":"Relapsed or refractory low-grade, follicular or transformed B-cell NHL including rituximab-refractory follicular lymphoma"},{"region":"US","year":2009,"indication":"Consolidation after first-line chemotherapy in previously untreated follicular NHL"},{"region":"EU","year":2004,"indication":"Rituximab-relapsed or refractory CD20-positive follicular lymphoma; first-line consolidation added 2008"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ibritumomab-tiuxetan/"}
{"id":"illuccix","kind":"drug","name":"Illuccix (kit for Ga-68 gozetotide)","aka":[],"tldr":"Telix's ready-to-label kit that lets any nuclear medicine department make the gallium PSMA scan for prostate cancer.","summary":"Illuccix was approved by the FDA in December 2021 for PET imaging of PSMA-positive lesions in men with suspected metastasis who are candidates for definitive therapy and in men with suspected recurrence based on rising PSA, and in 2025 the label was extended to selecting patients for PSMA radioligand therapy. Gozellix, a second-generation kit with longer post-labelling shelf life, was approved in 2025. Illuccix is also registered in Australia and several other markets. The kit format made PSMA PET available to centres without access to the cyclotron-produced 18F tracers.","status":"approved","asOf":"2026-09-10","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Illuccix"}],"tags":["test"],"related":["ga68-psma-11","locametz","pylarify","f-18","ga-68"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":["psma"],"drugs":["pluvicto"],"companies":["telix"],"institutions":[],"pathways":[],"terms":["biochemical-recurrence","theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What a result means: PSMA-avid spots on the scan indicate prostate cancer deposits and decide between local treatment, systemic therapy or radioligand therapy."],"brand":"Illuccix / Gozellix","modality":"PET imaging agent kit (PSMA, gallium-68)","mechanism":"Kit for on-site labelling of PSMA-11 (gozetotide) with gallium-68 from a generator or cyclotron; the tracer binds PSMA on prostate cancer cells for PET imaging.","approvals":[{"region":"US","year":2021,"indication":"PSMA PET imaging in prostate cancer (initial staging with suspected metastasis; suspected recurrence)"},{"region":"Australia","year":2021,"indication":"PSMA PET imaging in prostate cancer"},{"region":"US","year":2025,"indication":"Gozellix kit; selection of patients for PSMA-targeted radioligand therapy"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/illuccix/"}
{"id":"iobenguane-i-131","kind":"drug","name":"Iobenguane I-131 (therapeutic)","aka":["131I-MIBG","Ultratrace iobenguane"],"tldr":"Azedra was a radioactive drug that homed in on adrenal-type tumours (phaeochromocytoma and paraganglioma) that could not be removed and delivered radiation from inside. It was approved in 2018 and discontinued by its maker in 2024.","summary":"High-specific-activity iobenguane I-131 (Azedra) was approved by the FDA in July 2018 for adults and children aged 12 and over with iobenguane scan-positive, unresectable, locally advanced or metastatic phaeochromocytoma or paraganglioma requiring systemic therapy, on a single-arm phase 2 study in which a quarter of patients halved their antihypertensive medication for at least six months and most had tumour control. It was the first approved therapy for these tumours. Progenics (later Lantheus) discontinued manufacture in 2024, so patients rely on compounded low-specific-activity 131I-MIBG or lutetium-177 dotatate. Myelosuppression, secondary MDS and leukaemia, hypothyroidism and renal toxicity were the main risks; the diagnostic-dose iobenguane (AdreView) is an imaging agent covered separately.","status":"withdrawn","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Iobenguane","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=iobenguane"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/iobenguanei131"}],"tags":["nci-list"],"related":["lutathera","lu-177","i-131"],"indications":["neuroendocrine"],"sections":[],"technologies":["mibg-theranostics","radioligand-therapy"],"targets":[],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":["radioiodine-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Phaeochromocytoma and paraganglioma have no cancer record yet; linked to neuroendocrine tumours."],"brand":"Azedra","modality":"Radiopharmaceutical therapy (beta and gamma emitter)","mechanism":"Noradrenaline analogue taken up by the noradrenaline transporter into chromaffin and neuroendocrine tumour cells; iodine-131 beta emission delivers targeted radiation.","approvals":[{"region":"US","year":2018,"indication":"Iobenguane scan-positive unresectable, locally advanced or metastatic phaeochromocytoma or paraganglioma in patients 12 and older (discontinued 2024)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/iobenguane-i-131/"}
{"id":"iomab-b","kind":"drug","name":"Iomab-B","aka":["Apamistamab-I131","131I-apamistamab"],"tldr":"Iomab-B is Actinium's radioactive antibody that clears the bone marrow before a transplant for older patients with active relapsed acute myeloid leukaemia; the phase 3 SIERRA trial met its primary endpoint but the FDA asked for another study.","summary":"Iomab-B delivers iodine-131 to CD45-positive cells, allowing patients with relapsed or refractory acute myeloid leukaemia who would not tolerate conventional myeloablative conditioning to proceed to allogeneic transplant. In the phase 3 SIERRA trial, Iomab-B followed by transplant produced durable complete remission at six months in a substantially higher share of patients than conventional care. Actinium reported in 2024 that the FDA requested an additional randomised trial before filing, and it is seeking partners; the trial is recorded here.","status":"phase-3","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov: trials of Iomab-B","url":"https://clinicaltrials.gov/search?intr=Iomab-B"}],"tags":["pipeline","ctgov-ingest"],"related":["i-131"],"indications":[],"sections":[],"technologies":["radioimmunotherapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":["actinium-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["nct02665065"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2, curated)","editedOn":"2026-09-16"},"modality":"Radioimmunotherapy conditioning agent (anti-CD45 antibody labelled with iodine-131)","mechanism":"An antibody against CD45, found on all white blood cells, carries iodine-131 to the marrow and leukaemia cells and ablates them in place of high-dose chemotherapy before a stem cell transplant.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/iomab-b/"}
{"id":"itm-11","kind":"drug","name":"177Lu-edotreotide","aka":[],"tldr":"A second lutetium radioligand for neuroendocrine tumours that beat the standard pill everolimus in a head-to-head trial and is awaiting an FDA decision.","summary":"COMPETE (Lancet 2025; 309 patients, grade 1-2 GEP-NETs): PFS 23.9 vs 14.1 months versus everolimus (HR 0.67); response rate higher; interim OS 63.4 vs 58.7 months, a difference that did not reach statistical significance (HR 0.78). Uses non-carrier-added 177Lu from ITM's own supply. NDA accepted with PDUFA 28 August 2026. COMPOSE (grade 2-3, versus CAPTEM/everolimus/FOLFOX) ongoing.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03049189 (COMPETE)","url":"https://clinicaltrials.gov/study/NCT03049189"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine","grade-3-net"],"sections":[],"technologies":["prrt","radioligand-therapy"],"targets":["sstr2"],"drugs":[],"companies":["itm"],"institutions":[],"pathways":[],"terms":[],"trials":["compete","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"ITM-11, n.c.a. 177Lu-DOTATOC","modality":"Radioligand therapy (beta)","mechanism":"DOTATOC peptide (SSTR2 agonist) chelating 177Lu; four cycles of 7.5 GBq every 3 months.","approvals":[],"mechanismSteps":[],"dosing":{"route":"Intravenous","schedule":"7.5 GBq every 3 months × 4 with amino-acid renal protection"},"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2025-03","type":"designation","region":"US","note":"COMPETE topline at ENETS 2025","source":"https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-presents-positive-topline-phase-3-compete-trial-data-with-nca-177lu-edotreotide-itm-11-a-targeted-radiopharmaceutical-therapy-in-patients-with-grade-1-or-2-gastroenteropancreatic-neuroendocrine-tumors-at-the-enets-2025-conference-688/"},{"date":"2026-08-28","type":"pdufa","region":"US","note":"PDUFA goal date for GEP-NET indication","source":"https://www.cancernetwork.com/view/fda-accepts-new-drug-application-for-177lu-edotreotide-in-gep-nets"}],"route":"/drugs/itm-11/"}
{"id":"jnj-87189401","kind":"drug","name":"JNJ-87189401","aka":[],"tldr":"JNJ-87189401 is an experimental costimulatory agent from Janssen Research & Development in phase 3 trials for prostate cancer, aimed at PSMA.","summary":"JNJ-87189401 is a costimulatory agent developed by Janssen Research & Development. Its target is PSMA (the sponsor names PSMA / CD28). The sponsor states: A PSMA-CD28 costimulatory agent intended to enhance T-cell activation via PSMA engagement plus CD28 costimulation. It is the investigational product in 1 recruiting or active industry-led phase 2 and phase 3 interventional cancer trial, including the phase 3 study NCT07164443 (A Study of Pasritamig With or Without JNJ-87189401 Versus Placebo for Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC)), in prostate cancer. The largest, NCT07164443, plans to enrol 1203 participants with primary completion expected 2028-08-18. Status reflects the highest phase registered on ClinicalTrials.gov; no efficacy results are recorded here.","status":"phase-3","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov: trials of JNJ-87189401","url":"https://clinicaltrials.gov/search?intr=JNJ-87189401"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":["mcrpc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor pipeline pages)","editedOn":"2026-09-11"},"modality":"costimulatory bispecific antibody (PSMA x CD28, per the sponsor's pipeline page)","mechanism":"A PSMA-CD28 costimulatory agent intended to enhance T-cell activation via PSMA engagement plus CD28 costimulation.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/jnj-87189401/"}
{"id":"locametz","kind":"drug","name":"Locametz (kit for Ga-68 gozetotide)","aka":[],"tldr":"Novartis' gallium PSMA scan kit, approved the same day as Pluvicto as the test that qualifies men for that radioactive drug.","summary":"Locametz was approved by the FDA on 23 March 2022, alongside Pluvicto (lutetium-177 vipivotide tetraxetan), with an explicit indication for selecting patients with metastatic castration-resistant prostate cancer for PSMA-directed therapy, as well as for initial staging and biochemical recurrence. The European Commission approved it in December 2022. It is manufactured by Advanced Accelerator Applications, the Novartis radiopharmaceutical unit, and was the first PSMA PET agent approved in the EU. The scan-then-treat pairing is the template for theranostics.","status":"approved","asOf":"2026-09-10","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Locametz"}],"tags":["test"],"related":["ga68-psma-11","illuccix","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","pet-ct","radioligand-therapy"],"targets":["psma"],"drugs":["pluvicto"],"companies":["novartis","advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":["vision"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["What a result means: enough PSMA uptake on the scan is required before Pluvicto can be given; a scan without uptake means the drug is unlikely to work."],"brand":"Locametz","modality":"PET imaging agent kit (PSMA, gallium-68)","mechanism":"Kit for on-site labelling of gozetotide (PSMA-11) with gallium-68; the resulting tracer images PSMA-expressing prostate cancer and identifies candidates for lutetium-177 PSMA therapy.","approvals":[{"region":"US","year":2022,"indication":"PSMA PET in prostate cancer, including selection of patients for PSMA radioligand therapy"},{"region":"EU","year":2022,"indication":"PSMA PET in prostate cancer"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/locametz/"}
{"id":"lu177-psma-it","kind":"drug","name":"177Lu-PSMA-I&T","aka":[],"tldr":"177Lu-PSMA-I&T is a second PSMA radioligand, chemically different from Pluvicto, that has passed two phase 3 trials on progression but has not yet shown a survival benefit.","summary":"SPLASH (Lantheus PNT2002, ESMO 2024): rPFS 9.5 vs 6.0 months (HR 0.71) vs ARPI switch in taxane-naive mCRPC; interim OS HR 1.11 (immature, crossover). ECLIPSE (Curium, 7.4 GBq × 6): met rPFS endpoint vs ARPI in the same setting; OS maturing; FDA submission plan pending. Curium's Japanese registrational trial with PeptiDream started February 2026. Widely used off-protocol in Germany and Australia.","status":"phase-3","asOf":"2026-09-06","links":[{"label":"SPLASH primary analysis (Lantheus, ESMO 2024)","url":"https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-presents-results-primary-analysis-phase-3-pivotal"},{"label":"ECLIPSE meets rPFS (OncLive)","url":"https://www.onclive.com/view/177lu-psma-i-t-meets-rpfs-end-point-in-psma-mcrpc"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma"],"drugs":[],"companies":["lantheus","curium"],"institutions":[],"pathways":[],"terms":[],"trials":["splash","eclipse-psma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"PNT2002 (Lantheus); Curium 177Lu-PSMA-I&T","modality":"Radioligand therapy (beta)","mechanism":"Urea-based PSMA ligand with DOTAGA chelator carrying 177Lu; beta emission.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/lu177-psma-it/"}
{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","aka":[],"tldr":"Lutetium-177 dotatate was the first modern radioligand therapy (2018), for neuroendocrine tumours, and is now used in first line.","summary":"Lutetium-177 dotatate is a radioligand therapy: the somatostatin analogue DOTATATE binds SSTR2 on neuroendocrine tumour cells and carries the beta emitter 177Lu into them, irradiating over a few millimetres. NETTER-1 established it in midgut NETs progressing on octreotide, and NETTER-2 (2024) moved it into first line for higher grade-2 and grade-3 GEP-NETs with PFS 22.8 versus 8.5 months. It was approved in 2018 for SSTR-positive GEP-NETs, with paediatric use from age 12 added in 2024. Dosing is 7.4 GBq every 8 weeks for 4 doses with an amino acid infusion to protect the kidneys; lymphopenia is common, and myelodysplastic syndrome (2.3%) and acute leukaemia (0.5%) are rare late risks. Alpha-emitting successors RYZ101 and AlphaMedix are in phase 3. The first generic is queued behind the patents: on 21 September 2026 FDA tentatively approved Lantheus's ANDA 217060 (Bravnetsa, 10 mCi/mL), finding it bioequivalent to Lutathera (NDA 208700), but withheld final approval because Advanced Accelerator Applications (Novartis) is suing Lantheus over US patent 10,596,276 in the District of Delaware (Civil Action No. 24-00095); final approval waits for the 30-month stay to run out, a court ruling that the patent is invalid or not infringed, or the patent's expiry on 25 January 2039. For a newcomer: the first modern radioligand therapy and the template for a whole class.","status":"approved","asOf":"2026-10-04","wikipedia":"https://en.wikipedia.org/wiki/Lutetium_(177Lu)_oxodotreotide","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lutetium-177%20dotatate"},{"label":"Drugs@FDA: ANDA 217060, Bravnetsa (Lantheus), tentative approval","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217060"},{"label":"FDA tentative approval letter, ANDA 217060 (21 Sep 2026)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/217060Orig1s000TAltr.pdf"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine","small-intestinal-net","pancreatic-net","grade-3-net","metastatic-ppgl"],"sections":[],"technologies":["radioligand-therapy"],"targets":["sstr2"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["prrt-term"],"trials":["netter-1","nct04711135","nct05142696","nct03972488"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Lutathera","code":"177Lu-DOTATATE","modality":"Radioligand therapy (beta)","mechanism":"SSTR2 agonist peptide with 177Lu.","approvals":[{"region":"US","year":2018,"indication":"SSTR+ GEP-NETs"},{"region":"US","year":2024,"indication":"Paediatric ≥12 years; first-line (NETTER-2 label)"},{"region":"EU","year":2017,"indication":"First approval globally (Sep 2017)"}],"mechanismSteps":["Radioligand circulates and binds Somatostatin receptor 2 on tumour cells","Ligand is internalised or retained at the membrane","Beta emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV infusion","schedule":"7.4 GBq (200 mCi) every 8 weeks for 4 doses, with amino acid infusion starting 30 minutes before and continuing ≥3 hours","modifications":"Hold for grade ≥3 haematologic toxicity or renal toxicity; discontinue after 16-week delay","monitoring":"Blood counts, creatinine, LFTs before each dose; long-term MDS/AML surveillance","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55"},"toxicity":[{"event":"Lymphopenia","grade3PlusPct":44,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"GGT increased","grade3PlusPct":20,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"Vomiting","grade3PlusPct":7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"Nausea","grade3PlusPct":5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"AST increased","grade3PlusPct":5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"ALT increased","grade3PlusPct":4,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"Hyperglycaemia","grade3PlusPct":4,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"Hypokalaemia","grade3PlusPct":4,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"},{"event":"Myelodysplastic syndrome","anyGradePct":2.3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"Median onset 29 months"},{"event":"Acute leukaemia","anyGradePct":0.5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","note":"NETTER-1; grade 3-4 rates"}],"access":[{"country":"US","listPrice":"~$47,500 per dose (launch price 2018)","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended for unresectable/metastatic GEP-NETs (TA539)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2017-09-26","type":"approval","region":"EU","note":"EMA approval: first modern PRRT","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2018-01-26","type":"approval","region":"US","note":"SSTR+ gastroenteropancreatic NETs (NETTER-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-04-23","type":"approval","region":"US","note":"Paediatric patients ≥12 years","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-06","type":"label-change","region":"US","note":"First-line label based on NETTER-2","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/lutathera/"}
{"id":"olaparib","kind":"drug","name":"Olaparib","aka":[],"tldr":"Olaparib was the first PARP inhibitor, and turned an inherited BRCA mutation from a risk factor into a drug target, including after surgery in breast cancer.","summary":"Approved 2014 (ovarian), then maintenance first-line (SOLO-1, 7-year OS benefit), with bevacizumab (PAOLA-1, HRD+), metastatic BRCA breast (OlympiAD), adjuvant germline-BRCA HER2-negative early breast cancer (OlympiA, OS HR 0.72), pancreatic maintenance (POLO), and prostate (PROfound; PROpel with abiraterone). AstraZeneca/Merck.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Olaparib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Olaparib"}],"tags":[],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["parp"],"drugs":[],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06909825"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Lynparza","modality":"Small-molecule PARP inhibitor","mechanism":"PARP1/2 inhibitor and trapper; synthetic lethality with HRD.","approvals":[{"region":"US","year":2014,"indication":"gBRCA ovarian cancer ≥3 lines"},{"region":"US","year":2018,"indication":"gBRCA HER2- metastatic breast cancer"},{"region":"US","year":2022,"indication":"Adjuvant gBRCA high-risk HER2- early breast cancer"}],"mechanismSteps":["Olaparib binds PARP1/2 at sites of single-strand DNA breaks","PARP is trapped on DNA and repair of single-strand breaks stops","Replication forks collide with trapped PARP and collapse into double-strand breaks","BRCA-deficient cells cannot repair the breaks by homologous recombination","Genomic catastrophe and apoptosis in tumour cells; normal cells with intact BRCA survive"],"dosing":{"route":"Oral","schedule":"300 mg twice daily; 1 year adjuvant (OlympiA); 2 years first-line ovarian maintenance; until progression otherwise","modifications":"200 mg BID for moderate renal impairment; hold for grade ≥3 anaemia; discontinue for MDS/AML or pneumonitis","monitoring":"Blood counts monthly; respiratory symptoms; embryo-fetal counselling","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa"},"toxicity":[{"event":"Nausea","anyGradePct":57,"grade3PlusPct":0.8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Fatigue","anyGradePct":42,"grade3PlusPct":1.8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Anaemia","anyGradePct":24,"grade3PlusPct":9,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Vomiting","anyGradePct":23,"grade3PlusPct":0.7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Diarrhoea","anyGradePct":18,"grade3PlusPct":0.3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Leukopenia","anyGradePct":17,"grade3PlusPct":3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Neutropenia","anyGradePct":16,"grade3PlusPct":5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"MDS/AML","anyGradePct":1.2,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"Cumulative across trials; 54% fatal"},{"event":"Pneumonitis","anyGradePct":1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"},{"event":"Venous thromboembolism (prostate)","anyGradePct":8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa","note":"OlympiA adjuvant, n=911"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.astrazeneca-us.com/medicines/access-360","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended in ovarian maintenance (TA598, TA620), adjuvant gBRCA breast (TA886), metastatic breast (TA1100), prostate (TA887)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"},{"country":"EU","reimbursement":"EMA approved across indications","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2014-12-19","type":"approval","region":"US","note":"gBRCA advanced ovarian cancer after ≥3 lines: first PARP inhibitor","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2017-08-17","type":"approval","region":"US","note":"Maintenance in platinum-sensitive recurrent ovarian cancer; tablet formulation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2018-01-12","type":"approval","region":"US","note":"gBRCA HER2-negative metastatic breast cancer (OlympiAD)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2018-12-19","type":"approval","region":"US","note":"First-line maintenance in BRCA-mutated ovarian cancer (SOLO-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2019-12-27","type":"approval","region":"US","note":"gBRCA metastatic pancreatic cancer maintenance (POLO)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-05-19","type":"approval","region":"US","note":"HRR-mutant mCRPC (PROfound)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-03-11","type":"approval","region":"US","note":"Adjuvant gBRCA high-risk HER2-negative early breast cancer (OlympiA)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2023-05-31","type":"approval","region":"US","note":"With abiraterone in BRCA-mutated mCRPC (PROpel)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/olaparib/"}
{"id":"pasireotide","kind":"drug","name":"Pasireotide","aka":["SOM230"],"tldr":"Pasireotide is a second-generation somatostatin analogue that hits more receptor types than octreotide. It is approved for Cushing's disease and acromegaly caused by pituitary tumours when surgery has not cured them, at the cost of frequent high blood sugar.","summary":"Pasireotide (SOM230) was developed by Novartis and is now marketed by Recordati. The FDA approved the twice-daily subcutaneous form in 2012 for Cushing's disease when surgery is not an option or has failed, the first drug approved for that indication, and the monthly long-acting depot in 2014 for acromegaly inadequately controlled by surgery. It normalises cortisol in a minority and growth hormone and IGF-1 in a larger fraction of patients, and shrinks tumours in many.\n\nHyperglycaemia, from suppression of insulin and incretins, is the main side effect and often needs treatment. Beyond the pituitary, the phase 2 LUNA trial tested it alone and with everolimus in lung and thymic neuroendocrine tumours and found activity in each arm, without a placebo comparison. The pituitary tumours and lung neuroendocrine tumour pages name it.","status":"approved","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Pasireotide","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pasireotide"}],"tags":["subtype-drugs-wave"],"related":["everolimus"],"indications":["lung-net"],"sections":[],"technologies":[],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Signifor / Signifor LAR","modality":"Multireceptor somatostatin analogue (subcutaneous or monthly depot)","mechanism":"Binds somatostatin receptors 1, 2, 3 and 5, with far higher affinity for SSTR5 than octreotide; SSTR5 dominates on corticotroph adenomas, so it suppresses ACTH in Cushing's disease and growth hormone in acromegaly resistant to first-generation analogues.","approvals":[{"region":"US","year":2012,"indication":"Cushing's disease when pituitary surgery is not an option or has not been curative"},{"region":"US","year":2014,"indication":"Acromegaly inadequately controlled by surgery or for whom surgery is not an option (long-acting depot)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/pasireotide/"}
{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","aka":[],"tldr":"Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.","summary":"Approvals span melanoma, NSCLC, head and neck, Hodgkin, urothelial, MSI-H/dMMR tumours (first tumour-agnostic approval, 2017), gastric, oesophageal, cervical, HCC, RCC, endometrial, TNBC (KEYNOTE-355 metastatic CPS ≥10; KEYNOTE-522 neoadjuvant/adjuvant with 7-year OS benefit), TMB-high, and more. 2026 additions include platinum-resistant PD-L1+ ovarian cancer, adjuvant RCC with belzutifan, and combination labels with sacituzumab govitecan (ASCENT-04) and enfortumab vedotin. Subcutaneous Keytruda Qlex approved 2025. Backbone for neoantigen vaccines (intismeran).","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Pembrolizumab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Pembrolizumab"}],"tags":[],"related":[],"indications":["hcc","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Keytruda / Keytruda Qlex (SC)","modality":"Monoclonal antibody (anti-PD-1)","mechanism":"Humanised IgG4 blocking PD-1; restores T-cell effector function.","approvals":[{"region":"US","year":2014,"indication":"Melanoma (first of >40 indications)"},{"region":"US","year":2017,"indication":"MSI-H/dMMR solid tumours (tumour-agnostic)"},{"region":"US","year":2020,"indication":"Metastatic TNBC, PD-L1 CPS ≥10, with chemotherapy"},{"region":"US","year":2021,"indication":"High-risk early TNBC, neoadjuvant + adjuvant (KEYNOTE-522)"},{"region":"US","year":2026,"indication":"Platinum-resistant PD-L1+ ovarian cancer; adjuvant RCC with belzutifan; with sacituzumab govitecan in 1L TNBC"}],"mechanismSteps":["Antibody binds PD-1 on T cells","PD-1/PD-L1 engagement between T cell and tumour is blocked","Exhausted tumour-reactive T cells regain effector function","Interferon-γ and cytotoxic granules are released at the tumour","Tumour cells are killed; memory T cells persist"],"dosing":{"route":"IV infusion over 30 min (subcutaneous Keytruda Qlex available)","schedule":"200 mg every 3 weeks or 400 mg every 6 weeks; paediatric 2 mg/kg (max 200 mg) every 3 weeks; up to 24 months in most metastatic settings","modifications":"Hold for grade 2 immune-mediated events; permanently discontinue for grade 4 or recurrent grade 3","monitoring":"Thyroid function, LFTs, creatinine, glucose at baseline and periodically; patient education on immune-related symptoms","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287"},"toxicity":[{"event":"Hypothyroidism (immune-mediated)","anyGradePct":8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Pneumonitis (immune-mediated)","anyGradePct":3.4,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Colitis (immune-mediated)","anyGradePct":1.7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Hepatitis (immune-mediated)","anyGradePct":0.7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Fatigue","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Musculoskeletal pain","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Rash","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Diarrhoea","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"},{"event":"Pyrexia","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","note":"Pooled monotherapy data, >2,800 patients"}],"access":[{"country":"US","listPrice":"$11,564 per 200 mg dose (WAC, Merck price disclosure 2024)","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.merckaccessprogram-keytruda.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended across many indications (melanoma, NSCLC, TNBC KEYNOTE-522/355, RCC, HNSCC, cervical, oesophageal and others)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"},{"country":"EU","reimbursement":"EMA approved; reimbursed in all member states for core indications","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2014-09-04","type":"approval","region":"US","note":"Accelerated approval, advanced melanoma after ipilimumab; first PD-1 inhibitor in the US","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2015-10-02","type":"approval","region":"US","note":"PD-L1+ NSCLC after platinum","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2017-05-23","type":"approval","region":"US","note":"MSI-H/dMMR solid tumours: first tumour-agnostic approval","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-06-16","type":"approval","region":"US","note":"TMB-high solid tumours (tumour-agnostic)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-11-13","type":"approval","region":"US","note":"Metastatic TNBC, PD-L1 CPS ≥10, with chemotherapy (KEYNOTE-355)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2021-07-26","type":"approval","region":"US","note":"High-risk early TNBC, neoadjuvant and adjuvant (KEYNOTE-522)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2023-10-16","type":"approval","region":"US","note":"Perioperative NSCLC (KEYNOTE-671)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-09","type":"approval","region":"US","note":"Subcutaneous pembrolizumab (Keytruda Qlex)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-Q1","type":"approval","region":"US","note":"Platinum-resistant PD-L1+ ovarian cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-06-12","type":"approval","region":"US","note":"Adjuvant RCC with belzutifan (LITESPARK-022)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma"},{"date":"2026-06-24","type":"approval","region":"US","note":"First-line PD-L1+ TNBC with sacituzumab govitecan (ASCENT-04)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line"},{"date":"2026-07-10","type":"approval","region":"US","note":"Muscle-invasive bladder cancer with enfortumab vedotin, as pembrolizumab or pembrolizumab with berahyaluronidase alfa","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-or-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-enfortumab-vedotin"}],"route":"/drugs/pembrolizumab/"}
{"id":"phosphorus-32","kind":"drug","name":"Phosphorus-32 (radiophosphorus)","aka":["Radiophosphorus","Sodium phosphate P-32","32P"],"tldr":"Radiophosphorus was one of the first treatments for polycythaemia vera, from the 1940s: a radioactive phosphate injection that quietened the overactive bone marrow for a year or more. It was abandoned when trials showed it raised the risk of leukaemia.","summary":"Phosphorus-32 was introduced by John Lawrence at Berkeley in the late 1930s as the first therapeutic use of an artificial radionuclide, and became a standard treatment for polycythaemia vera and essential thrombocythaemia. A single intravenous dose controlled blood counts for one to two years and was convenient for older patients.\n\nThe Polycythemia Vera Study Group's first randomised trial, launched in 1967, compared phlebotomy alone, phlebotomy plus radiophosphorus and phlebotomy plus chlorambucil, and showed that both radiophosphorus and chlorambucil raised the risk of acute leukaemia several-fold. Radiophosphorus was thereafter restricted to the very elderly and is now rarely used, replaced by hydroxyurea, interferon and JAK inhibitors. The polycythaemia vera page records it in the history of the disease.","status":"historic","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Phosphorus-32","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phosphorus-32"}],"tags":["subtype-drugs-wave"],"related":["p-32"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"Intravenous radiopharmaceutical (beta emitter; historic)","mechanism":"Phosphate labelled with the beta emitter phosphorus-32 is taken up by rapidly dividing marrow cells and incorporated into their DNA, where the radiation suppresses the overactive marrow of polycythaemia vera.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/phosphorus-32/"}
{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","aka":[],"tldr":"A radioactive drug that seeks out PSMA on prostate cancer cells; the best-selling radiopharmaceutical ever.","summary":"VISION (2021): OS 15.3 vs 11.3 months in post-chemotherapy mCRPC. PSMAfore (2023) led to a 2025 label before chemotherapy. July 2026 FDA action further expanded the label (per AACR/FDA roundups). PSMAddition tests it in hormone-sensitive disease. Requires PSMA PET positivity. Six cycles every 6 weeks; xerostomia, cytopenias, renal monitoring.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Lutetium_(177Lu)_vipivotide_tetraxetan","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lutetium-177%20vipivotide%20tetraxetan"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc","prostate-mhspc"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","nct05682443","nct06894511","nct06004661"],"people":["louise-emmett"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Pluvicto","code":"177Lu-PSMA-617","modality":"Radioligand therapy (beta)","mechanism":"Small-molecule PSMA ligand chelated to 177Lu; beta emission with 2 mm range.","approvals":[{"region":"US","year":2022,"indication":"PSMA+ mCRPC after ARPI and taxane"},{"region":"US","year":2025,"indication":"PSMA+ mCRPC after ARPI, before chemotherapy"},{"region":"US","year":2026,"indication":"Label expansion (July 2026)"},{"region":"EU","year":2022,"indication":"mCRPC post-ARPI and taxane; pre-chemo 2025"}],"mechanismSteps":["Radioligand circulates and binds PSMA on tumour cells","Ligand is internalised or retained at the membrane","Beta emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV injection","schedule":"7.4 GBq (200 mCi) every 6 weeks for up to 6 doses","modifications":"Hold for grade ≥3 myelosuppression or renal impairment; permanently discontinue for grade 4 haematologic toxicity","monitoring":"Blood counts and renal function before each dose; hydration; radiation-protection instructions for 7 days","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a"},"toxicity":[{"event":"Lymphocytes decreased","anyGradePct":85,"grade3PlusPct":47,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Haemoglobin decreased","anyGradePct":64,"grade3PlusPct":15,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Fatigue","anyGradePct":48,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Dry mouth","anyGradePct":39,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Nausea","anyGradePct":36,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Decreased appetite","anyGradePct":21,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"},{"event":"Platelets decreased","grade3PlusPct":9,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","note":"VISION"}],"access":[{"country":"US","listPrice":"~$42,500 per dose (Novartis, 2022 launch price)","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.novartis.com/us-en/patient-support","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended for PSMA+ mCRPC after ARPI and taxane (2025); pre-chemotherapy appraisal in progress","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-06","type":"designation","region":"US","note":"Breakthrough Therapy designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-03-23","type":"approval","region":"US","note":"PSMA+ mCRPC after ARPI and taxane (VISION)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-12","type":"approval","region":"EU","note":"EMA approval","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-03-28","type":"approval","region":"US","note":"PSMA+ mCRPC after ARPI, before chemotherapy (PSMAfore)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-07-31","type":"approval","region":"US","note":"PSMA+ metastatic hormone-sensitive prostate cancer with ARPI (PSMAddition)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/pluvicto/"}
{"id":"psma-1007-f18","kind":"drug","name":"PSMA-1007 F-18","aka":["Prostalumin"],"tldr":"PSMA-1007 is a fluorine-18 PSMA PET tracer from ABX in Germany, widely used in Europe for prostate cancer staging because little of it reaches the bladder, and in a phase 3 trial registered by its maker.","summary":"PSMA-1007, developed at Heidelberg and manufactured by ABX advanced biochemical compounds in Radeberg, is a fluorine-18 PSMA ligand whose low urinary excretion improves views of the prostate bed and pelvic nodes. It is authorised in several European countries and Canada and used in many centres alongside gallium-68 PSMA-11 and piflufolastat; a phase 3 trial by ABX is registered on ClinicalTrials.gov. Health Canada's Drug Product Database lists PROSTALUMIN ((18F)PSMA-1007, 3.7 GBq/mL intravenous solution, DIN 02571757) from the Centre for Probe Development and Commercialization in Hamilton, Ontario, with status Approved and a product monograph dated 24 September 2026.","status":"phase-3","asOf":"2026-10-04","links":[{"label":"ClinicalTrials.gov: trials of PSMA-1007 F-18","url":"https://clinicaltrials.gov/search?intr=PSMA-1007%20F-18"},{"label":"Health Canada Drug Product Database: PROSTALUMIN, DIN 02571757","url":"https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=107378"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18","ga-68"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","pet"],"targets":["psma"],"drugs":[],"companies":["abx-advanced-biochemical-compounds"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06122584"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2, curated)","editedOn":"2026-09-16"},"modality":"PSMA-targeted PET radiotracer, fluorine-18","mechanism":"A fluorine-18 PSMA ligand excreted mainly through the liver rather than the kidneys, so the bladder does not obscure the prostate bed on PET.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/psma-1007-f18/"}
{"id":"pylarify","kind":"drug","name":"Piflufolastat F-18 / Pylarify TruVu","aka":[],"tldr":"Piflufolastat F-18 (Pylarify) is the leading PSMA PET tracer for prostate cancer, with a new formulation approved in March 2026.","summary":"Piflufolastat F-18 is a PET tracer: an 18F-labelled urea that binds prostate-specific membrane antigen (PSMA), lighting up prostate cancer deposits that conventional CT and bone scan miss. It was approved in 2021 for PSMA PET in initial staging and biochemical recurrence, and Lantheus' Pylarify TruVu formulation, approved on 9 March 2026, offers an improved formulation and distribution profile. A single 333 MBq dose is injected and imaging follows 60 to 120 minutes later; adverse effects are minor. The 18F label allows central manufacture and shipping, unlike generator-produced 68Ga agents, and it competes with Illuccix/Gozellix (68Ga, Telix), Locametz (Novartis) and Posluma. The open question is whether the management changes PSMA PET triggers translate into longer survival. For a newcomer: the leading tracer for seeing where prostate cancer actually is.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Piflufolastat_F-18","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Piflufolastat%20F-18"}],"tags":[],"related":["f-18","ga-68"],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Pylarify","code":"18F-DCFPyL","modality":"PET imaging agent","mechanism":"18F-labelled PSMA-binding urea.","approvals":[{"region":"US","year":2021,"indication":"PSMA PET imaging in prostate cancer"},{"region":"US","year":2026,"indication":"Pylarify TruVu formulation"},{"region":"EU","year":2023,"indication":"EU brand Pylclari (Curium)"}],"mechanismSteps":["18F-labelled small molecule binds the PSMA active site","Tracer is internalised and retained in prostate cancer cells","Positron emissions are detected by the PET scanner","Whole-body map of PSMA-expressing disease is produced","Result selects patients for PSMA radioligand therapy"],"dosing":{"route":"IV injection (diagnostic)","schedule":"333 MBq (9 mCi) single dose; imaging 60-120 minutes later","monitoring":"Hydration and voiding to reduce bladder dose","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Headache","note":"Rare; diagnostic dose"},{"event":"Dysgeusia"},{"event":"Fatigue"}],"access":[{"country":"US","reimbursement":"Medicare pass-through/payment for PSMA PET; broad commercial coverage for staging and biochemical recurrence","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-05-26","type":"approval","region":"US","note":"PSMA PET imaging in prostate cancer: first 18F PSMA agent","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-03-09","type":"approval","region":"US","note":"Pylarify TruVu formulation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/pylarify/"}
{"id":"radioactive-iodine","kind":"drug","name":"Radioactive iodine (I-131)","aka":[],"tldr":"The original targeted radiotherapy: thyroid cells soak up iodine, so radioactive iodine destroys leftover thyroid tissue and metastases while sparing everything else.","summary":"In use since 1946 for differentiated thyroid cancer; the archetype of theranostics (I-123 or I-131 scans image the same uptake). Roles: remnant ablation after thyroidectomy (now omitted in low-risk disease after ESTIMABL2, IoN, HiLo), adjuvant treatment of intermediate/high-risk disease, and treatment of iodine-avid metastases. Given after TSH stimulation (withdrawal or recombinant TSH). Salivary damage, secondary malignancy at high cumulative doses, and refractoriness in dedifferentiated tumours are the limits.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Iodine-131","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Radioactive%20iodine"}],"tags":[],"related":["i-123","i-131"],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy","radioligand-therapy"],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics","radioiodine-term"],"trials":["hilo","estimabl2","ion-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Sodium iodide I-131","modality":"Radiopharmaceutical (beta/gamma emitter, natural uptake)","mechanism":"Sodium-iodide symporter (NIS) concentrates iodide in thyroid follicular cells; I-131 beta particles (mean path ~0.8 mm) irradiate the cell and neighbours; gamma emission enables imaging.","approvals":[{"region":"US","year":1951,"indication":"Hyperthyroidism and thyroid carcinoma (first radiopharmaceutical approval)"}],"mechanismSteps":["TSH stimulation upregulates the sodium-iodide symporter on thyroid cells","Oral I-131 is absorbed and concentrated in thyroid tissue and iodine-avid metastases","Beta decay deposits radiation within ~1 mm, killing the cells over weeks","Gamma emission allows a post-therapy scan to map uptake"],"dosing":{"route":"Oral capsule or solution","schedule":"1.1 GBq (30 mCi) for remnant ablation (HiLo); 3.7-7.4 GBq for adjuvant or metastatic treatment; low-iodine diet and TSH stimulation beforehand","monitoring":"Post-therapy whole-body scan; thyroglobulin; salivary and marrow function","source":"https://www.thyroid.org/professionals/ata-professional-guidelines/"},"toxicity":[{"event":"Sialadenitis / xerostomia","source":"https://www.thyroid.org/professionals/ata-professional-guidelines/","note":"Dose-dependent; common after repeated high-activity treatment"}],"access":[],"regulatoryEvents":[{"date":"1946","type":"approval","region":"US","note":"First therapeutic use in thyroid cancer (Seidlin); formal approval followed"}],"route":"/drugs/radioactive-iodine/"}
{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","aka":[],"tldr":"Radium-223 was the first alpha-emitting drug ever approved (2013). It homes to bone like calcium and treats prostate cancer that has spread only to bone.","summary":"Radium-223 is a calcium mimetic incorporated into bone matrix at sites of metastatic bone turnover, where each decay chain delivers four alpha emissions over a range of a few cells, killing tumour while largely sparing marrow. It is given intravenously to men with symptomatic castration-resistant prostate cancer whose spread is confined to bone without visceral disease. ALSYMPCA showed overall survival of 14.9 versus 11.3 months (HR 0.70) and fewer skeletal events, and it became the first alpha-emitting drug ever approved (2013). ERA 223 showed excess fractures when combined with abiraterone, now contraindicated without bone protection, while PEACE III (2024) with enzalutamide plus bone-protecting agents was positive for rPFS and overall survival. How to sequence it with 177Lu-PSMA therapy is unresolved. Simply put, it is a radioactive calcium look-alike that homes to bone metastases.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Radium-223","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Radium-223%20dichloride"}],"tags":[],"related":["lu-177","ra-223"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":["bayer"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":["alsympca"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Xofigo","modality":"Targeted alpha therapy (bone-seeking)","mechanism":"Calcium mimetic incorporated into bone matrix at metastases; four alpha emissions per decay chain.","approvals":[{"region":"US","year":2013,"indication":"Symptomatic bone-metastatic CRPC without visceral disease"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/radium-223/"}
{"id":"rituximab","kind":"drug","name":"Rituximab","aka":["Rituximab and Hyaluronidase Human","Rituxan Hycela"],"tldr":"Rituximab was the first antibody ever approved for cancer (1997). It made chemoimmunotherapy the CLL standard for a decade, and biosimilars keep it cheap and everywhere.","summary":"Approved in follicular lymphoma (1997), DLBCL (2006, R-CHOP), CLL (2010, with fludarabine-cyclophosphamide: FCR, the first regimen to show OS benefit in CLL). Superseded in CLL by targeted agents (CLL13, CLL14, ELEVATE-TN) but still used with venetoclax in relapse (MURANO: venetoclax-rituximab 24 months) and in resource-limited settings. Biosimilars (Truxima, Ruxience, Riabni) since 2018.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Rituximab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Rituximab"}],"tags":[],"related":[],"indications":["dlbcl"],"sections":[],"technologies":[],"targets":["cd20"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Rituxan / MabThera (and biosimilars)","modality":"Monoclonal antibody (anti-CD20, chimeric)","mechanism":"Chimeric type I anti-CD20 IgG1: CDC, ADCC, and modest direct signalling.","approvals":[{"region":"US","year":1997,"indication":"Relapsed follicular lymphoma; first antibody approved for cancer"},{"region":"US","year":2010,"indication":"CLL with fludarabine and cyclophosphamide"}],"mechanismSteps":["Binds CD20 and clusters it into lipid rafts","Complement is fixed (CDC) and NK cells recruited (ADCC)","B cells and CLL cells are lysed; normal B cells recover after 6-12 months"],"dosing":{"route":"IV or subcutaneous (Rituxan Hycela)","schedule":"CLL: 375 mg/m² cycle 1 then 500 mg/m² cycles 2-6 with chemotherapy or venetoclax","monitoring":"Infusion reactions, HBV reactivation (boxed), PML (boxed), late-onset neutropenia","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Rituxan"},"toxicity":[{"event":"Infusion-related reactions (first infusion)","anyGradePct":77,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Rituxan","note":"Historic lymphoma data; lower with premedication"},{"event":"Hepatitis B reactivation","note":"Boxed warning; screen all patients"},{"event":"Late-onset neutropenia","anyGradePct":8}],"access":[],"regulatoryEvents":[],"route":"/drugs/rituximab/"}
{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","aka":[],"tldr":"An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version.","summary":"RYZ101 is actinium-225 DOTATATE, a targeted alpha therapy: the same SSTR2-binding peptide as Lutathera but chelating 225Ac, whose alpha decay chain delivers dense, short-range double-strand DNA breaks that beta particles cannot match. Bristol Myers Squibb acquired it with RayzeBio in 2024 for $4.1B. The ACTION-1 phase 3 trial tests it in SSTR-positive GEP-NETs progressing after 177Lu-SSTR therapy, at 10.5 MBq/kg every 8 weeks for 4 cycles, and it is also being combined with chemo-immunotherapy in extensive-stage small-cell lung cancer. Nausea, fatigue and lymphopenia are expected, and renal function is monitored because the kidneys clear the peptide. Whether alpha emission overcomes resistance to beta therapy, and whether 225Ac supply can meet demand, are the open questions. For a newcomer: an alpha-particle upgrade of an approved neuroendocrine radioligand.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Actinium-225 DOTATATE","url":"https://clinicaltrials.gov/search?intr=RYZ101"}],"tags":[],"related":["lu-177","ac-225"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["sstr2"],"drugs":[],"companies":["bms","rayzebio"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06590857"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"RYZ101","modality":"Targeted alpha therapy","mechanism":"DOTATATE chelating 225Ac; alpha decay chain.","approvals":[],"mechanismSteps":["Radioligand circulates and binds Somatostatin receptor 2 on tumour cells","Ligand is internalised or retained at the membrane","Alpha (225Ac) emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV infusion","schedule":"10.5 MBq/kg every 8 weeks for 4 cycles (ACTION-1)","monitoring":"Renal function, blood counts, amino acid co-infusion","source":"https://clinicaltrials.gov/study/NCT05477576"},"toxicity":[{"event":"Nausea"},{"event":"Fatigue"},{"event":"Lymphopenia"},{"event":"Renal toxicity (monitor)"}],"access":[{"country":"US","reimbursement":"Investigational","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-02-26","type":"filing","region":"US","note":"BMS completes RayzeBio acquisition ($4.1B)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}],"route":"/drugs/ryz101/"}
{"id":"samarium-153-lexidronam","kind":"drug","name":"Samarium-153 lexidronam","aka":["153Sm-EDTMP","Samarium Sm 153 lexidronam pentasodium"],"tldr":"Quadramet (samarium-153 lexidronam) is a radioactive bone-seeking injection that lodges in bone metastases and irradiates them from inside, approved in 1997 to relieve pain from prostate, breast and other cancers spread to bone. Most patients get relief within one to two weeks, but marrow suppression follows at three to five weeks, and radium-223 and PSMA radioligands have largely replaced it.","summary":"Samarium-153 lexidronam was approved by the FDA in March 1997 and authorised in the EU in February 1998 for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that take up technetium-labelled bisphosphonate on bone scan, on placebo-controlled trials in which most patients had pain relief within one to two weeks lasting for months. It and strontium-89 (Metastron) were the bone-pain radiopharmaceuticals of the 1990s; radium-223 (Xofigo), which extends survival in prostate cancer, and PSMA radioligands have since taken most of their role. A single intravenous dose is given; transient marrow suppression, with nadir at three to five weeks, is the main toxicity, and a pain flare can occur early. Distributed by Lantheus in the US and Curium in Europe.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Samarium_(153Sm)_lexidronam","links":[{"label":"EPAR (EMA)","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/quadramet"},{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=samarium"}],"tags":["ema-list","supportive"],"related":["radium-223","ra-223","sm-153","sr-89"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":["lantheus","curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Quadramet","modality":"Bone-seeking therapeutic radiopharmaceutical (beta emitter)","mechanism":"Samarium-153 chelated to the tetraphosphonate EDTMP concentrates in areas of high bone turnover around osteoblastic metastases; beta emission (1.9 day half-life) irradiates the metastases and relieves pain, with gamma emission allowing imaging.","approvals":[{"region":"US","year":1997,"indication":"Relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan"},{"region":"EU","year":1998,"indication":"Relief of bone pain from multiple painful osteoblastic skeletal metastases (Quadramet)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/samarium-153-lexidronam/"}
{"id":"sorafenib","kind":"drug","name":"Sorafenib","aka":[],"tldr":"The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.","summary":"SHARP: OS 10.7 vs 7.9 months versus placebo (HR 0.69). Standard first-line therapy for a decade until REFLECT (lenvatinib non-inferior) and IMbrave150 (atezolizumab-bevacizumab superior). Also approved in RCC and radioiodine-refractory thyroid cancer. Hand-foot skin reaction and diarrhoea dominate toxicity.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Sorafenib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Sorafenib"}],"tags":[],"related":[],"indications":["hcc","rcc","thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["bayer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Nexavar","modality":"Small-molecule multi-kinase inhibitor (VEGFR, PDGFR, RAF)","mechanism":"Oral inhibitor of VEGFR1-3, PDGFR-β, KIT, FLT3 and RAF kinases; anti-angiogenic and anti-proliferative.","approvals":[{"region":"US","year":2005,"indication":"Advanced RCC"},{"region":"US","year":2007,"indication":"Unresectable HCC"},{"region":"US","year":2013,"indication":"Radioiodine-refractory differentiated thyroid cancer"}],"mechanismSteps":["Enters tumour and endothelial cells","Blocks VEGFR/PDGFR signalling in vessels, cutting blood supply","Inhibits RAF-MEK-ERK in tumour cells","Tumour growth slows; rarely shrinks"],"dosing":{"route":"Oral","schedule":"400 mg twice daily continuously","modifications":"Dose reduction to 400 mg daily for grade 2-3 hand-foot skin reaction","monitoring":"Blood pressure, skin, liver function"},"toxicity":[{"event":"Diarrhoea","anyGradePct":39,"grade3PlusPct":8,"note":"SHARP"},{"event":"Hand-foot skin reaction","anyGradePct":21,"grade3PlusPct":8,"note":"SHARP"},{"event":"Fatigue","anyGradePct":22,"grade3PlusPct":4,"note":"SHARP"}],"access":[],"regulatoryEvents":[{"date":"2007-11-16","type":"approval","region":"US","note":"Unresectable HCC on SHARP"}],"route":"/drugs/sorafenib/"}
{"id":"sunitinib","kind":"drug","name":"Sunitinib","aka":[],"tldr":"Sunitinib is an anti-angiogenic pill approved for pancreatic neuroendocrine tumours, kidney cancer and GIST.","summary":"Sunitinib is an oral inhibitor of VEGFR1-3, PDGFR, KIT, FLT3 and RET that blocks tumour blood-vessel growth and, in GIST, the KIT driver itself. It is approved for advanced renal cell carcinoma and imatinib-resistant GIST (2006), progressive pancreatic neuroendocrine tumours (2011, 37.5 mg daily continuously) and, little used, as adjuvant therapy in high-risk RCC (S-TRAC, 2017). The pancreatic NET phase 3 (Raymond 2011) showed PFS of 11.4 versus 5.5 months and was stopped early for benefit. In kidney cancer it has been largely displaced by immunotherapy combinations and is the control arm they beat in CheckMate 214, KEYNOTE-426, CheckMate 9ER and CLEAR, while it is still standard second line in GIST. Fatigue, diarrhoea, hand-foot syndrome, hypertension and hypothyroidism are common. For a newcomer, sunitinib defined first-line kidney cancer treatment before immunotherapy.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Sunitinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Sunitinib"}],"tags":[],"related":[],"indications":["neuroendocrine","rcc","metastatic-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In kidney cancer: Motzer 2007 showed PFS 11 versus 5 months against interferon alfa and OS 26.4 versus 21.8 months, and sunitinib then served as the control arm of CheckMate 214, KEYNOTE-426, CheckMate 9ER and CLEAR; it is now mainly used in favourable-risk disease, where immunotherapy doublets show no OS gain, and in GIST, and has been generic since 2021. Resistance runs through alternative angiogenic pathways (FGF, MET, AXL)."],"brand":"Sutent","modality":"Small-molecule multi-kinase inhibitor (VEGFR, PDGFR, KIT)","mechanism":"Oral inhibitor of VEGFR1-3, PDGFR, KIT, FLT3, RET.","approvals":[{"region":"US","year":2006,"indication":"Advanced RCC; GIST after imatinib"},{"region":"US","year":2011,"indication":"Progressive pancreatic NETs"},{"region":"US","year":2017,"indication":"Adjuvant RCC at high risk (S-TRAC), little used"}],"mechanismSteps":[],"dosing":{"route":"Oral","schedule":"37.5 mg daily continuously (pNET)","monitoring":"Blood pressure, thyroid, cardiac function"},"toxicity":[{"event":"Diarrhoea","anyGradePct":59},{"event":"Nausea","anyGradePct":45},{"event":"Hypertension","anyGradePct":26,"grade3PlusPct":10},{"event":"Hand-foot syndrome","anyGradePct":23,"grade3PlusPct":6}],"access":[],"regulatoryEvents":[],"route":"/drugs/sunitinib/"}
{"id":"technetium-sulfur-colloid","kind":"drug","name":"Technetium Tc-99m sulfur colloid","aka":["Tc-99m sulphur colloid"],"tldr":"Technetium sulfur colloid is the radioactive tracer injected around a breast cancer or melanoma before surgery so the surgeon can find the first lymph node the tumour drains to and remove only that node instead of the whole basin.","summary":"Technetium-99m sulfur colloid has been used for liver, spleen and bone marrow scintigraphy since the 1970s, and the FDA label was extended to lymphatic mapping to localise lymph nodes draining a primary breast tumour or melanoma. Sentinel node biopsy guided by the tracer, often with blue dye, replaced routine axillary dissection in breast cancer and elective node dissection in melanoma after the NSABP B-32 and MSLT-I trials, sparing most patients lymphoedema. Tilmanocept (Lymphoseek), a purpose-designed mannose receptor agent, is the newer alternative.","status":"established","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Technetium_(99mTc)_sulfur_colloid","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Technetium_(99mTc)_sulfur_colloid"},{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=technetium%20tc%2099m%20sulfur%20colloid"}],"tags":["gap-fill","chembl-universe"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Technetium Tc 99m Sulfur Colloid Kit","modality":"Radiopharmaceutical for lymphatic mapping and liver, spleen and marrow imaging","mechanism":"Colloidal particles labelled with technetium-99m are taken up by macrophages; injected near a tumour they drain to and lodge in the first (sentinel) lymph nodes, which a gamma probe then finds during surgery.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/technetium-sulfur-colloid/"}
{"id":"temozolomide","kind":"drug","name":"Temozolomide","aka":[],"tldr":"The only chemotherapy proven to extend life in glioblastoma, given during and after radiation. It works best when the tumour has switched off a repair gene called MGMT.","summary":"Stupp/EORTC 26981-NCIC (2005): adding concurrent and adjuvant temozolomide to radiotherapy raised median OS from 12.1 to 14.6 months and 2-year survival from 10% to 27%. Benefit concentrates in MGMT-promoter-methylated tumours (median OS ~23 months vs ~13 months unmethylated). Also standard with radiotherapy in grade 3 astrocytoma (CATNON) and, with PCV as an alternative, in oligodendroglioma. Oral, well tolerated; lymphopenia and hypermutation at recurrence are the costs.","status":"standard-of-care","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Temozolomide","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Temozolomide"}],"tags":[],"related":[],"indications":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04919226"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Temodar","modality":"Oral alkylating chemotherapy","mechanism":"Prodrug of MTIC; methylates O6-guanine; cytotoxicity depends on unrepaired lesions when MGMT is silenced.","approvals":[{"region":"US","year":1999,"indication":"Refractory anaplastic astrocytoma"},{"region":"US","year":2005,"indication":"Newly diagnosed glioblastoma with radiotherapy"},{"region":"EU","year":1999,"indication":"Temodal; malignant glioma (recurrent 1999; newly diagnosed glioblastoma with radiotherapy 2005); 26 Jan 1999"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/temozolomide/"}
{"id":"thyrotropin-alfa","kind":"drug","name":"Thyrotropin alfa","aka":["Recombinant human TSH","rhTSH"],"tldr":"Thyrogen is an injected version of thyroid-stimulating hormone that lets people with thyroid cancer have radioiodine treatment and follow-up blood tests without stopping their thyroid hormone tablets and suffering weeks of hypothyroidism.","summary":"Thyrotropin alfa was approved by the FDA in November 1998 as an adjunctive diagnostic tool for serum thyroglobulin testing with or without radioiodine imaging in the follow-up of well-differentiated thyroid cancer, and in 2007 for pre-therapeutic stimulation before radioiodine remnant ablation after thyroidectomy in patients without distant metastases; the EU authorised Thyrogen in 2000 with the same uses. The HiLo and ESTIMABL trials showed that rhTSH-stimulated low-dose (1.1 GBq) radioiodine ablation is as effective as high-dose ablation after thyroid hormone withdrawal, sparing patients hypothyroid symptoms and reducing radiation exposure. Nausea and headache are the main adverse effects; transient tumour swelling can occur with CNS or spinal metastases. Marketed by Sanofi (Genzyme).","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Thyrotropin_alfa","links":[{"label":"EPAR (EMA)","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/thyrogen"},{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=thyrotropin%20alfa"}],"tags":["ema-list","supportive"],"related":[],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radioiodine-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Thyrogen","modality":"Recombinant human thyroid-stimulating hormone","mechanism":"Recombinant TSH stimulates iodine uptake and thyroglobulin release from thyroid remnants and differentiated thyroid cancer cells, allowing radioiodine ablation and thyroglobulin testing without stopping levothyroxine.","approvals":[{"region":"US","year":1998,"indication":"Adjunctive diagnostic tool for thyroglobulin testing in well-differentiated thyroid cancer; pre-therapeutic stimulation for radioiodine remnant ablation added 2007"},{"region":"EU","year":2000,"indication":"Thyroglobulin testing and radioiodine imaging in thyroid cancer follow-up; pre-therapeutic stimulation for radioiodine ablation"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/thyrotropin-alfa/"}
{"id":"tilmanocept-tc99m","kind":"drug","name":"Technetium-99m tilmanocept","aka":[],"tldr":"The purpose-built tracer for sentinel lymph node mapping in breast cancer, melanoma and oral cancer, replacing off-label sulfur colloid.","summary":"Technetium-99m tilmanocept is a mannosylated dextran labelled with technetium-99m that binds CD206, the mannose receptor on macrophages in lymph nodes. Because it is small it drains rapidly from the injection site, and because it binds a receptor it stays in the sentinel node rather than passing through to second-echelon nodes, which simplifies surgery. It was the first agent purpose-built for sentinel lymph node mapping, replacing off-label sulfur colloid. The FDA approved it in March 2013 for breast cancer and melanoma, in 2014 for sentinel node localisation in oral cavity squamous cell carcinoma, where mapping showed 97.8% sensitivity, and extended it to children in 2017; the EU approved it in 2014. It is detected with a handheld gamma counter in theatre. Tilmanocept finds the first node a cancer would spread to so that only that node needs removal.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Tilmanocept","links":[{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Lymphoseek"}],"tags":["gap-fill","diagnostic"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":["spect"],"targets":[],"drugs":[],"companies":["navidea"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Lymphoseek","modality":"Radiopharmaceutical lymphatic mapping agent","mechanism":"Mannosylated dextran that binds CD206 (mannose receptor) on macrophages in sentinel nodes, giving rapid uptake and low pass-through to second-echelon nodes.","approvals":[{"region":"US","year":2013,"indication":"Lymphatic mapping with a handheld gamma counter in breast cancer and melanoma"},{"region":"US","year":2014,"indication":"Sentinel lymph node localisation in oral cavity squamous cell carcinoma"},{"region":"EU","year":2014,"indication":"Sentinel node imaging in breast cancer, melanoma, oral SCC"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tilmanocept-tc99m/"}
{"id":"abdera-therapeutics","kind":"company","name":"Abdera Therapeutics","aka":[],"tldr":"Abdera Therapeutics engineered antibodies that carry a radioactive isotope to cancer cells, tuning how long they circulate so more radiation reaches the tumour and less reaches healthy tissue. Its first medicine targets a protein on small cell lung cancer.","summary":"Abdera Therapeutics, based in Vancouver and Menlo Park, California, developed antibody-based radiopharmaceuticals using its ROVEr antibody engineering platform, which tunes pharmacokinetic properties so that alpha- or beta-emitting isotopes can be matched to targets with a wide range of antigen expression. Its lead programme targets DLL3 for small cell lung cancer and other solid tumours and was advancing toward the clinic at launch; founding partners were adMare BioInnovations and AbCellera. The company emerged in April 2023 with USD 142 million in combined Series A and B financing, the Series A led by Versant Ventures and Amplitude Ventures and the USD 110 million Series B led by venBio Partners with Viking Global Investors, Qiming Venture Partners USA and RTW Investments.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.biospace.com/abdera-therapeutics-debuts-with-142-million-in-financing-to-engineer-and-advance-best-in-class-antibody-based-radiopharmaceuticals-for-cancer"},{"label":"Endpoints News: Abdera raises $110M Series B","url":"https://endpoints.news/abdera-raises-110m-to-push-targeted-radiotherapies-where-they-havent-gone-before/"}],"tags":[],"related":[],"indications":["sclc"],"sections":[],"technologies":["radioimmunotherapy","targeted-alpha-therapy","radioligand-therapy"],"targets":["dll3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Company website abderatx.com returned HTTP 503 or no response on every attempt, so the website field points to the fetched press release copy instead. Current status is uncertain: search headlines in 2026 refer to an auction of Abdera laboratory equipment and to biotechs that closed, but no fetched primary source confirms a wind-down, so stage is left at startup. Clinical status of the DLL3 programme (a phase 1a start was reported in trade press) not confirmed from fetched pages."],"hq":"Vancouver","country":"CA","companyType":"radiopharma","website":"https://www.biospace.com/abdera-therapeutics-debuts-with-142-million-in-financing-to-engineer-and-advance-best-in-class-antibody-based-radiopharmaceuticals-for-cancer","stage":"startup","investors":[],"funding":[{"round":"Series B","year":2023,"amountUsd":110000000,"source":"https://endpoints.news/abdera-raises-110m-to-push-targeted-radiotherapies-where-they-havent-gone-before/","note":"Led by venBio Partners; the company's launch release reports USD 142 million in combined Series A and B financing"}],"route":"/companies/abdera-therapeutics/"}
{"id":"abx-advanced-biochemical-compounds","kind":"company","name":"ABX advanced biochemical compounds","aka":["ABX advanced biochemical compounds GmbH","ABX GmbH","ABX"],"tldr":"ABX is a German maker of the precursors and kits behind PET imaging tracers, including PSMA agents for prostate cancer, and sponsors the trials that register them.","summary":"ABX advanced biochemical compounds, based in Radeberg near Dresden, manufactures radiopharmaceutical precursors, cold kits and labelling chemistry used to produce PET tracers, among them PSMA-directed agents for prostate cancer imaging developed with the German Cancer Research Center. It acts as lead sponsor of phase 3 diagnostic trials registered on ClinicalTrials.gov.","asOf":"2026-09-11","links":[{"label":"Official website","url":"https://www.abx.de"},{"label":"ClinicalTrials.gov: trials led by ABX advanced biochemical compounds","url":"https://clinicaltrials.gov/search?lead=ABX%20advanced%20biochemical%20compounds"}],"tags":["ctgov-sponsor"],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":["psma-1007-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Radeberg","country":"DE","companyType":"pharma","website":"https://www.abx.de","stage":"private-large","investors":[],"funding":[],"route":"/companies/abx-advanced-biochemical-compounds/"}
{"id":"acrotech-biopharma","kind":"company","name":"Acrotech Biopharma","aka":[],"tldr":"Acrotech Biopharma, part of Aurobindo, owns the former Spectrum Pharmaceuticals haematology portfolio: the radioimmunotherapy Zevalin, pralatrexate (Folotyn), belinostat (Beleodaq) and vincristine liposome (Marqibo).","summary":"Acrotech Biopharma, based in East Windsor, New Jersey, and part of Aurobindo, owns the former Spectrum Pharmaceuticals haematology portfolio: the radioimmunotherapy Zevalin, pralatrexate as Folotyn, belinostat as Beleodaq and vincristine liposome as Marqibo. It acquired Spectrum's marketed products in 2019, including Zevalin, or ibritumomab tiuxetan, for follicular lymphoma, Folotyn and Beleodaq for peripheral T-cell lymphoma, Marqibo and Evomela, a melphalan formulation. Nuclide links it to the ibritumomab tiuxetan drug record. Whether the only approved radioimmunotherapy for lymphoma survives commercially in an owner focused on generics is the open question. Ibritumomab tiuxetan has its own page.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.acrotechbiopharma.com"}],"tags":[],"related":[],"indications":["follicular-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["ibritumomab-tiuxetan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"East Windsor, New Jersey","country":"US","companyType":"pharma","website":"https://www.acrotechbiopharma.com","investors":[],"funding":[],"route":"/companies/acrotech-biopharma/"}
{"id":"actinium-pharmaceuticals","kind":"company","name":"Actinium Pharmaceuticals","aka":[],"tldr":"Actinium Pharmaceuticals attaches the alpha-emitting isotope actinium-225 to antibodies to treat acute myeloid leukaemia and, more recently, solid tumours such as prostate and lung cancer. It is a small listed company whose lead programme is approaching new clinical milestones.","summary":"Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), headquartered in New York, develops targeted radiotherapies based on actinium-225 antibody radioconjugates and holds proprietary Ac-225 manufacturing technology. The lead programme Actimab-A is a CD33-targeting, mutation-agnostic therapy for relapsed or refractory acute myeloid leukaemia, with patents extending to solid tumours via myeloid-derived suppressor cells; the company expects clinical milestones from the fourth quarter of 2026. ATNM-400 is a first-in-class Ac-225 pan-tumour radiotherapy in preclinical development for metastatic castration-resistant prostate cancer, non-small cell lung cancer and breast cancer, with 2026 SNMMI data in androgen receptor inhibitor-resistant prostate models and KRAS and EGFR mutant lung models. Iomab-ACT is a targeted conditioning programme. In 2026 the company received NYSE American listing standards notices and appointed Steffen Heeger as Chief Medical Officer.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.actiniumpharma.com/"},{"label":"August 2026 Actimab-A and listing update","url":"https://ir.actiniumpharma.com/press-releases/detail/525/actinium-pharmaceuticals-announces-actimab-a-intellectual"},{"label":"Press releases","url":"https://ir.actiniumpharma.com/press-releases"}],"tags":[],"related":["ac-225"],"indications":["prostate"],"sections":[],"technologies":["radioimmunotherapy","targeted-alpha-therapy"],"targets":[],"drugs":["iomab-b"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Ticker, exchange and HQ confirmed via SEC EDGAR submissions data (CIK 0001388320). Public company; no private rounds listed. Founding year not sourced."],"hq":"New York, NY","country":"US","companyType":"radiopharma","website":"https://www.actiniumpharma.com/","ticker":"ATNM","stage":"public","investors":[],"funding":[],"route":"/companies/actinium-pharmaceuticals/"}
{"id":"advanced-accelerator-applications","kind":"company","name":"Advanced Accelerator Applications (Novartis)","aka":[],"tldr":"The CERN spin-out that Novartis bought in 2018 for Lutathera, which now makes Pluvicto and the Locametz and Netspot imaging kits.","summary":"Advanced Accelerator Applications, based in Saint-Genis-Pouilly, France, and founded in 2002, is the CERN spin-out that Novartis bought in 2018 for Lutathera, and it now makes Pluvicto and the Locametz and Netspot imaging kits. AAA developed Lutathera, or 177Lu-DOTATATE, and the Netspot gallium-68 DOTATATE kit before its 3.9 billion dollar acquisition, and as Novartis' radioligand unit it manufactures Locametz, the gallium-68 PSMA-11 kit, and Pluvicto and runs the Novartis radioligand production network in Europe and the United States. Nuclide links it to prostate cancer and neuroendocrine tumours, to PSMA PET, somatostatin receptor PET and beta-emitter radioligand therapy, and to Novartis. Whether its production network can meet demand as radioligand indications widen is the open question. Locametz and Pluvicto have their own pages.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.adacap.com"}],"tags":[],"related":["ga-68","lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["psma-pet","sstr-pet","radioligand-therapy"],"targets":[],"drugs":["locametz","ga68-dotatate","pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05849298","nct07047118","nct06784752","nct04939610","nct05658003","nct03972488","nct06247995"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Saint-Genis-Pouilly","country":"FR","companyType":"radiopharma","website":"https://www.adacap.com","founded":2002,"investors":[],"funding":[],"route":"/companies/advanced-accelerator-applications/"}
{"id":"aktis-oncology","kind":"company","name":"Aktis Oncology","aka":[],"tldr":"Miniprotein alpha-radiopharmaceutical company; the first biotech IPO of 2026 (~$365M) funds Ac-225 programmes against Nectin-4 and B7-H3.","summary":"Aktis Oncology, based in Boston and listed as AKTS, is a miniprotein alpha-radiopharmaceutical company whose IPO, closed on 12 January 2026 for about 365 million dollars, was the first biotech IPO of the year and funds actinium-225 programmes against Nectin-4 and B7-H3. Its lead, 225Ac-AKY-1189 against Nectin-4, is in a US phase 1b; 225Ac-AKY-2519 against B7-H3 has an IND planned for the first half of 2026 after diagnostic imaging and dosimetry studies; an in-house cGMP radiopharmaceutical facility is due in the second half of 2026; and large pharma investors back it. Nuclide links it to bladder, small-cell lung and prostate cancer, to targeted alpha therapy and alpha-emitter nanogenerators, and to Nectin-4 and B7-H3 as targets. Whether miniproteins can deliver alpha emitters safely is the open question. The targeted alpha therapy page carries the field.","asOf":"2026-09-04","links":[{"label":"IPO coverage","url":"https://www.fiercebiotech.com/biotech/1st-biotech-ipo-2026-sees-aktis-bring-318m-upsized-offering"}],"tags":["frontier"],"related":["ac-225"],"indications":["sclc","prostate"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["nectin4","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Boston, MA","country":"US","companyType":"radiopharma","website":"https://www.aktisoncology.com","ticker":"AKTS","investors":[],"funding":[],"route":"/companies/aktis-oncology/"}
{"id":"alpha-9-oncology","kind":"company","name":"Alpha-9 Oncology","aka":[],"tldr":"Alpha-9 Oncology designs bespoke molecules that deliver radioactive isotopes to cancer cells, with early human trials under way in melanoma and in breast and other solid tumours.","summary":"Alpha-9 Oncology is a clinical-stage radiopharmaceutical company with offices in Vancouver and Boston. It takes a modular approach, optimising each element of a radiotherapeutic (binder, linker, chelator and isotope) and pairing therapeutic agents with imaging companions. A9-3408, an actinium-225 radiotherapeutic targeting melanocortin 1 receptor (MC1R), began a phase 1 study in melanoma in December 2025, following the 68Ga imaging agent A9-3202 that entered the clinic in 2024. In September 2026 the company dosed the first patient in a phase 1 study of two GRPR-targeting compounds, 225Ac-A9-0642 and 177Lu-A9-0631, in breast cancer and other solid tumours, with data expected in late 2027. Alpha-9 has an actinium-225 supply agreement with ITM (April 2025). In October 2024 it closed an oversubscribed USD 175 million Series C led by Lightspeed Venture Partners and Ascenta Capital. Paul Blanchfield was appointed CEO in November 2025.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.a9oncology.com/"},{"label":"Series C press release","url":"https://www.a9oncology.com/alpha-9-oncology-inc-announces-175-million-oversubscribed-series-c-financing-to-advance-robust-clinical-pipeline-of-radiopharmaceuticals/"},{"label":"GRPR phase 1 first patient dosed","url":"https://www.a9oncology.com/alpha-9-oncology-doses-first-patient-in-phase-1-clinical-trial-evaluating-grpr-targeted-radiotherapeutics-across-multiple-solid-tumors/"}],"tags":[],"related":["ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The older domain alpha9oncology.com is now parked; current site is a9oncology.com. Earlier rounds not fetched."],"hq":"Vancouver","country":"CA","companyType":"radiopharma","website":"https://www.a9oncology.com/","stage":"growth","investors":[],"funding":[{"round":"Series C","year":2024,"amountUsd":175000000,"source":"https://www.a9oncology.com/alpha-9-oncology-inc-announces-175-million-oversubscribed-series-c-financing-to-advance-robust-clinical-pipeline-of-radiopharmaceuticals/"}],"route":"/companies/alpha-9-oncology/"}
{"id":"ansto","kind":"company","name":"ANSTO (Australian Nuclear Science and Technology Organisation)","aka":["ANSTO Nuclear Medicine"],"tldr":"ANSTO runs the OPAL research reactor near Sydney and a molybdenum-99 plant that supplies Australia's nuclear medicine and exports, and produces lutetium-177 for radioligand therapy.","summary":"The Australian Nuclear Science and Technology Organisation operates the OPAL reactor at Lucas Heights, commissioned in 2007, and the ANSTO Nuclear Medicine molybdenum-99 processing plant opened in 2019 to serve domestic technetium generators and export. It also produces non-carrier-added lutetium-177 and other isotopes and runs a national radiopharmaceutical distribution operation. Outages at the processing plant in its first years produced domestic shortages and imports from other processors.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.ansto.gov.au"}],"tags":["manufacturing-wave"],"related":["mo-99","lu-177"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain","radiopharmacy-network"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Lucas Heights, Sydney","country":"AU","companyType":"radiopharma","website":"https://www.ansto.gov.au","founded":1987,"stage":"private-large","investors":[],"funding":[],"route":"/companies/ansto/"}
{"id":"ariceum-therapeutics","kind":"company","name":"Ariceum Therapeutics","aka":[],"tldr":"Ariceum Therapeutics is a Berlin company developing a treatment that carries the alpha-emitting isotope actinium-225 to small cell lung cancer and Merkel cell skin cancer. Its first human trial began in late 2025.","summary":"Ariceum Therapeutics is a Berlin-based targeted radiotherapeutics company. Its lead candidate 225Ac-SSO110 is an actinium-225 labelled radioligand for extensive-stage small cell lung cancer (ES-SCLC) and Merkel cell carcinoma (MCC); the phase 1/2 SANTANA-225 study was planned to start in the second half of 2025, with initial safety data expected in early 2026 and preliminary efficacy findings in 2027. In August 2025 David Schilansky, previously CFO, succeeded co-founder Manfred Rüdiger as CEO alongside a new executive team.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.biospace.com/press-releases/ariceum-therapeutics-appoints-david-schilansky-as-chief-executive-officer-and-announces-new-leadership-to-advance-next-phase-of-development"}],"tags":[],"related":["ac-225"],"indications":["sclc"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Company website ariceum-therapeutics.com returned a certificate error and then an HTTP 500 'Database Error' on every attempt, so the website field points to the fetched release copy. Series A (reported elsewhere as EUR 25 million in 2022) and the Theragnostics acquisition are unsourced and omitted. SSO110 target (SSTR2 antagonist per other reports) not stated in the fetched text."],"hq":"Berlin","country":"DE","companyType":"radiopharma","website":"https://www.biospace.com/press-releases/ariceum-therapeutics-appoints-david-schilansky-as-chief-executive-officer-and-announces-new-leadership-to-advance-next-phase-of-development","stage":"startup","investors":[],"funding":[],"route":"/companies/ariceum-therapeutics/"}
{"id":"artbio","kind":"company","name":"ARTBIO","aka":[],"tldr":"ARTBIO makes cancer treatments that deliver short-range alpha radiation from lead-212 directly to tumour cells, starting with prostate cancer. Its first medicine is in early human trials, currently paused by the company while it reviews data.","summary":"ARTBIO, Inc. (Cambridge, Massachusetts, with engineering and manufacturing in Oslo) develops a new class of 212Pb alpha radioligand therapies (ARTs), together with its AlphaDirect isotope production technology and manufacturing ecosystem. The company was founded in 2021 by Roy Larsen and Øyvind Bruland, the inventors of Xofigo, with F-Prime and Radforsk. The lead asset AB001, a PSMA-targeted 212Pb radioligand for metastatic castration-resistant prostate cancer, is in the phase 1 ARTISAN trial; two cohorts (177Lu-PSMA naive and 177Lu-PSMA experienced) were dosed in January 2026, and in April 2026 the company implemented a voluntary clinical hold of ARTISAN. Jonathan Freeman was appointed interim CEO in July 2026. Further programmes include 212Pb antibody conjugates and the HEARTS discovery platform. ARTBIO raised a USD 90 million Series A in December 2023 and about USD 132 million in July 2025, according to Endpoints News.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://artbio.com/"},{"label":"ARTISAN cohort dosing release (PR Newswire)","url":"https://www.prnewswire.com/news-releases/artbio-announces-dosing-of-two-cohorts-with-ab001-in-artisan-a-phase-1-alpha-radioligand-therapy-clinical-trial-for-metastatic-castration-resistant-prostate-cancer-302657972.html"},{"label":"Endpoints News: Artbio raises $90M","url":"https://endpoints.news/artbio-raises-90m-as-radiopharma-field-finds-its-footing/"},{"label":"Endpoints News: Artbio attracts $132M","url":"https://endpoints.news/artbio-attracts-132m-as-its-alpha-radioligand-program-moves-into-the-clinic/"}],"tags":[],"related":["lu-177","pb-212"],"indications":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Endpoints article bodies are paywalled; amounts come from the visible headline and lede."],"hq":"Cambridge, MA","country":"US","companyType":"radiopharma","website":"https://artbio.com/","founded":2021,"stage":"startup","investors":[],"funding":[{"round":"Series A","year":2023,"amountUsd":90000000,"source":"https://endpoints.news/artbio-raises-90m-as-radiopharma-field-finds-its-footing/"},{"round":"Series B","year":2025,"amountUsd":132000000,"source":"https://endpoints.news/artbio-attracts-132m-as-its-alpha-radioligand-program-moves-into-the-clinic/","note":"Endpoints reports a USD 132 million raise in July 2025; the Series B label comes from the PR Newswire headline seen in search results, not from a fetched page"}],"route":"/companies/artbio/"}
{"id":"astrazeneca","kind":"company","name":"AstraZeneca","aka":["Acerta Pharma","Alexion Pharmaceuticals","MedImmune LLC","MedImmune"],"tldr":"AstraZeneca is the most ADC-committed large pharma, co-owner of Enhertu and Datroway, with deep targeted-therapy and radiopharma bets.","summary":"AstraZeneca's oncology revenue exceeds $20B. ADCs (T-DXd, Dato-DXd with Daiichi Sankyo; AZD0901 CLDN18.2; puxitatug samrotecan B7-H4; tilatamig samrotecan EGFR×MET bsADC), osimertinib, olaparib, capivasertib, durvalumab, camizestrant, saruparib, and radioconjugates via Fusion Pharma (225Ac-PSMA). Also cell therapy (Neogene, GPC3 CAR-T).","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/AstraZeneca","links":[{"label":"Official website","url":"https://www.astrazeneca.com"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib","durvalumab","ac225-psma","fpi-2265"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07611110","nct05219500","nct07590934","nct06909825","nct06040099"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Cambridge","country":"GB","companyType":"pharma","website":"https://www.astrazeneca.com","ticker":"AZN","investors":[],"funding":[],"route":"/companies/astrazeneca/"}
{"id":"atomic-alchemy","kind":"company","name":"Atomic Alchemy","aka":[],"tldr":"Atomic Alchemy set out to build small reactors dedicated to making the radioactive isotopes used in cancer scans and treatments, so hospitals no longer depend on a handful of ageing government reactors. It was bought by the nuclear company Oklo.","summary":"Atomic Alchemy planned the first privately owned reactors dedicated to radioisotope production, starting with molybdenum-99 for technetium imaging and extending to therapeutic isotopes whose scarcity holds back radiopharmaceutical trials. Its YC profile describes a supply chain reliant on six ageing research reactors abroad. The company was acquired by Oklo, an advanced fission developer, which announced the deal in late 2024 and closed it in 2025; Oklo is not an Nuclide record so the acquirer is named only here. Isotope production at scale remains a plan rather than an operating facility.","asOf":"2026-09-10","links":[{"label":"Y Combinator profile","url":"https://www.ycombinator.com/companies/atomic-alchemy"},{"label":"Official website","url":"https://atomicalchemy.us"}],"tags":["isotope-supply"],"related":["mo-99"],"indications":[],"sections":[],"technologies":["spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Idaho Falls, ID","country":"US","companyType":"radiopharma","website":"https://atomicalchemy.us","stage":"acquired","ycBatch":"W19","investors":[],"funding":[],"route":"/companies/atomic-alchemy/"}
{"id":"bayer","kind":"company","name":"Bayer","aka":[],"tldr":"Bayer owns Xofigo, the only approved alpha emitter, and is developing next-generation actinium PSMA agents.","summary":"Bayer, based in Leverkusen and listed as BAYN.DE, owns Xofigo, or radium-223, the only approved alpha emitter, and is developing next-generation actinium-225 PSMA agents. Its oncology portfolio includes 225Ac-PSMA-Trillium, also known as BAY 3563254, darolutamide in prostate cancer, sevabertinib for HER2-mutant non-small-cell lung cancer approved in 2025, larotrectinib, developed earlier with Lilly, and copanlisib, with the AlphaBreak and AcTION actinium trials linked in Nuclide. Nuclide also connects it to colorectal, liver, GIST and desmoid tumour pages, to the Norwegian Radium Hospital in Oslo, and to its venture arm Leaps by Bayer. Whether a targeted alpha emitter can go further than radium-223 did is the open question its PSMA programme will answer. Actinium-225 PSMA agents have their own page.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bayer","links":[{"label":"Official website","url":"https://www.bayer.com"}],"tags":[],"related":["ac-225","ra-223"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["ac225-psma"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Leverkusen","country":"DE","companyType":"pharma","website":"https://www.bayer.com","ticker":"BAYN.DE","investors":[],"funding":[],"route":"/companies/bayer/"}
{"id":"blue-earth-diagnostics","kind":"company","name":"Blue Earth Diagnostics (Bracco)","aka":[],"tldr":"Blue Earth Diagnostics makes Posluma (18F-rhPSMA-7.3) and Axumin (fluciclovine) PET agents for prostate cancer.","summary":"Blue Earth Diagnostics, based in Oxford and a subsidiary of Bracco, makes the PET imaging agents Posluma, or flotufolastat F-18, also written 18F-rhPSMA-7.3, and Axumin, or fluciclovine F-18, for prostate cancer. Posluma was approved in 2023 on the LIGHTHOUSE and SPOTLIGHT trials, and a therapeutic rhPSMA analogue is in development, which would extend the radiohybrid platform from imaging into treatment. Nuclide links it to prostate cancer and to both tracer records. Whether a fluorine-18 PSMA agent with a matched therapeutic can win share from the gallium-68 tracers already established is the open question. Flotufolastat and fluciclovine have their own pages.","asOf":"2026-09-06","links":[{"label":"Official website","url":"https://www.blueearthdiagnostics.com"}],"tags":[],"related":["f-18","ga-68"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["flotufolastat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07432633","nct07702292"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Oxford","country":"GB","companyType":"radiopharma","website":"https://www.blueearthdiagnostics.com","investors":[],"funding":[],"route":"/companies/blue-earth-diagnostics/"}
{"id":"bms","kind":"company","name":"Bristol Myers Squibb","aka":["Bristol-Myers Squibb","Juno Therapeutics","Mirati Therapeutics","Celgene","American Regent, Inc.","American Regent","YM BioSciences"],"tldr":"Pioneer of checkpoint inhibitors (Opdivo, Yervoy), now betting on the first successful bispecific ADC and alpha radiopharmaceuticals.","summary":"Bristol Myers Squibb, based in Princeton and listed as BMY, is the pioneer of checkpoint inhibitors with Opdivo and Yervoy, and it is now betting on the first successful bispecific antibody-drug conjugate and on alpha radiopharmaceuticals. Its portfolio spans nivolumab, ipilimumab and Opdualag, adagrasib from Mirati, the CAR-T products Breyanzi and Abecma, izalontamab brengitecan licensed from SystImmune for 8.4 billion dollars, actinium-225 DOTATATE from the 4.1 billion dollar RayzeBio purchase, and a PD-L1 by VEGF bispecific licensed from BioNTech for 11 billion dollars in 2025. Nuclide links it to the ten-year CheckMate 067 follow-up, CheckMate 649 and CheckMate 816 papers, to luspatercept, and to KRAS inhibitors and protein degradation. Whether its large bets on ADCs and radiopharmaceuticals pay off as the nivolumab franchise ages is the open question.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bristol_Myers_Squibb","links":[{"label":"Official website","url":"https://www.bms.com"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["ryz101"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Princeton, NJ","country":"US","companyType":"pharma","website":"https://www.bms.com","ticker":"BMY","investors":[],"funding":[],"route":"/companies/bms/"}
{"id":"boston-scientific","kind":"company","name":"Boston Scientific","aka":[],"tldr":"Medical device giant whose TheraSphere glass microspheres deliver yttrium-90 radioembolisation in liver cancer.","summary":"Boston Scientific, based in Marlborough, Massachusetts, and listed as BSX, is the medical device company whose TheraSphere glass microspheres deliver yttrium-90 radioembolisation in liver cancer. TheraSphere has held FDA approval for hepatocellular carcinoma since 2021, was studied in the EPOCH trial in colorectal liver metastases, which was positive for progression-free survival, and is being tested in combination with immunotherapy, and the company also sells drug-eluting embolic beads and other interventional oncology devices. Nuclide links it to hepatocellular carcinoma and colorectal cancer and to the radioembolisation and transarterial chemoembolisation technology records. Whether device-based liver-directed therapy keeps its role as systemic options improve is the open question. The technology pages carry the trial detail.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Boston_Scientific","links":[{"label":"Official website","url":"https://www.bostonscientific.com"}],"tags":[],"related":["y-90"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05063565"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Marlborough, MA","country":"US","companyType":"devices","website":"https://www.bostonscientific.com","ticker":"BSX","investors":[],"funding":[],"route":"/companies/boston-scientific/"}
{"id":"canon-medical","kind":"company","name":"Canon Medical Systems","aka":[],"tldr":"Canon Medical is the Japanese imaging vendor (formerly Toshiba Medical) with CT, MRI, ultrasound, and the Cartesion Prime PET/CT.","summary":"Canon Medical Systems, based in Otawara, Japan, is the imaging vendor formerly known as Toshiba Medical, with CT, MRI, ultrasound and the Cartesion Prime PET/CT. Its portfolio includes Aquilion CT and photon-counting development, Vantage MRI and PET/CT with digital detectors. Nuclide links it to nuclear medicine and total-body PET hardware, CT and MRI. Whether a fourth major imaging vendor can differentiate in PET and photon-counting CT against larger rivals is the open question. The PET hardware technology page carries the wider picture.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Canon_Medical_Systems_Corporation","links":[{"label":"Official website","url":"https://global.medical.canon"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["nuclear-medicine-hardware","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Otawara","country":"JP","companyType":"imaging","website":"https://global.medical.canon","investors":[],"funding":[],"route":"/companies/canon-medical/"}
{"id":"cardinal-health","kind":"company","name":"Cardinal Health Nuclear & Precision Health Solutions","aka":[],"tldr":"Nuclear pharmacy network (>130 sites) that compounds and delivers SPECT and PET doses, and a distributor of oncology drugs to community practices.","summary":"Cardinal Health Nuclear and Precision Health Solutions, based in Dublin, Ohio, and part of Cardinal Health, listed as CAH, is a nuclear pharmacy network of more than 130 sites that compounds and delivers SPECT and PET doses, and a distributor of oncology drugs to community practices. It is the largest US nuclear pharmacy chain and also a major distributor and group purchasing organisation for community oncology. Nuclide links it to radiopharmacy and cyclotron networks, PET tracer manufacturing and distribution and community oncology site networks, and to the FDG drug record. Whether its distribution reach can carry therapeutic radioligands to community practices as it does diagnostic doses is the open question. FDG has its own page.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.cardinalhealth.com"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["radiopharmacy-network","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Dublin, OH","country":"US","companyType":"radiopharma","website":"https://www.cardinalhealth.com","ticker":"CAH","investors":[],"funding":[],"route":"/companies/cardinal-health/"}
{"id":"cellectar","kind":"company","name":"Cellectar Biosciences","aka":["Cellectar Biosciences, Inc.","Cellectar"],"tldr":"Cellectar is a New Jersey radiopharmaceutical company whose iodine-131 phospholipid drug conjugate iopofosine targets the lipid rafts of cancer cells, with a pivotal trial (CLOVER-WaM) in relapsed Waldenström macroglobulinaemia.","summary":"Cellectar Biosciences, based in Florham Park, New Jersey and listed on Nasdaq, develops phospholipid drug conjugates that exploit the lipid rafts abundant on cancer cell membranes to deliver radioisotopes or cytotoxics. Its lead, iopofosine I-131 (CLR 131), delivers iodine-131 and reported its pivotal CLOVER-WaM results in relapsed Waldenström macroglobulinaemia in 2024; earlier studies covered multiple myeloma and paediatric high-grade glioma. It appears on Nuclide as a lead sponsor of phase 3 cancer trials on ClinicalTrials.gov.","asOf":"2026-09-11","links":[{"label":"Official website","url":"https://www.cellectar.com"},{"label":"ClinicalTrials.gov: trials led by Cellectar Biosciences","url":"https://clinicaltrials.gov/search?lead=Cellectar%20Biosciences"}],"tags":["ctgov-sponsor"],"related":["i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02952508"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Florham Park, NJ","country":"US","companyType":"radiopharma","website":"https://www.cellectar.com","stage":"public","investors":[],"funding":[],"route":"/companies/cellectar/"}
{"id":"clarity-pharmaceuticals","kind":"company","name":"Clarity Pharmaceuticals","aka":[],"tldr":"Clarity Pharmaceuticals, a Sydney radiopharmaceutical company, pairs copper isotopes with SAR-bisPSMA, a molecule that binds PSMA on prostate cancer cells: copper-64 for PET imaging, in the phase 3 AMPLIFY and CLARIFY trials, and copper-67 for therapy in the SECuRE trial. The copper-67 therapy is still at the dose-finding stage.","summary":"Co-PSMA head-to-head data (EAU 2026) showed Cu-64 SAR-bisPSMA more than doubled lesion and patient detection versus Ga-68 PSMA-11; FDA Fast Track in biochemical recurrence; commercial manufacturing agreement with Nucleus RadioPharma (April 2026). SECuRE therapy trial: 7 of 19 patients at 8 GBq 67Cu reached complete response or undetectable disease (July 2026).","asOf":"2026-09-04","links":[{"label":"SECuRE update","url":"https://www.prnewswire.com/news-releases/clarity-pharmaceuticals-announces-secure-trial-update-on-8-gbq-67cu-sar-bispsma-dose-level-with-two-additional-complete-responses-302843184.html"}],"tags":[],"related":["ga-68","cu-64","cu-67"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":["nct04868604"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Sydney","country":"AU","companyType":"radiopharma","website":"https://www.claritypharmaceuticals.com","ticker":"CU6.AX","investors":[],"funding":[],"route":"/companies/clarity-pharmaceuticals/"}
{"id":"comecer","kind":"company","name":"Comecer (ATS)","aka":[],"tldr":"Comecer, of Castel Bolognese, Italy, and part of ATS Corporation, makes hot cells, isolators and dose calibrators, the shielded enclosures and automation that radiopharmacies need to handle radioactive drugs aseptically. Therapeutic radioligands need more shielding than diagnostic tracers, and whether hospitals build enough of it is the open question.","summary":"Comecer, based in Castel Bolognese, Italy, and part of ATS Corporation, makes hot cells, isolators and dose calibrators for radiopharmacies. Its shielded enclosures and automation serve aseptic processing for radiopharmaceuticals and for cell therapies. Nuclide links it to medical cyclotrons, hot cells and synthesis modules. Whether hospitals build enough shielded capacity for therapeutic radioligands, which need more protection than diagnostic tracers, is the open question its products address. The cyclotron and synthesis technology page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.comecer.com"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["medical-cyclotrons-synthesis-modules"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Castel Bolognese","country":"IT","companyType":"radiopharma","website":"https://www.comecer.com","investors":[],"funding":[],"route":"/companies/comecer/"}
{"id":"convergent-therapeutics","kind":"company","name":"Convergent Therapeutics","aka":[],"tldr":"Convergent Therapeutics attaches an alpha-emitting isotope to an antibody that homes in on prostate cancer cells, for men whose disease has progressed after standard radioligand treatment. Its lead medicine has reported mid-stage trial results.","summary":"Convergent Therapeutics develops alpha radioantibodies: antibodies that deliver alpha-emitting payloads directly into cancer cells while limiting exposure of healthy tissue. The lead candidate CONV01-α is a PSMA-directed actinium-225 radioantibody for metastatic castration-resistant prostate cancer in patients previously treated with 177Lu-PSMA. In June 2026 the company presented what it described as the largest prospective phase 2 dataset for an alpha radiopharmaceutical at ASCO 2026, reporting anti-tumour activity, durability and favourable tolerability in Lu-PSMA-exposed mCRPC.","asOf":"2026-09-10","links":[{"label":"Official website","url":"http://convergentrx.com/"}],"tags":[],"related":["lu-177","ac-225"],"indications":["prostate"],"sections":[],"technologies":["radioimmunotherapy","targeted-alpha-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06549465"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The Business Wire releases (ASCO 2026 data, Series A) returned HTTP 403, so funding is omitted; trade press headlines report a USD 90 million Series A (2023) and a USD 40 million extension, unverified here. The domains convergenttx.com and convergenttherapeutics.com are parked; convergentrx.com blocks scripted requests but was fetched via WebFetch."],"hq":"Cambridge, MA","country":"US","companyType":"radiopharma","website":"http://convergentrx.com/","stage":"startup","investors":[],"funding":[],"route":"/companies/convergent-therapeutics/"}
{"id":"curium","kind":"company","name":"Curium","aka":[],"tldr":"Curium is one of the largest nuclear-medicine companies, developing 177Lu-PSMA-I&T (ECLIPSE) as a competitor to Pluvicto.","summary":"Curium is a Paris-based private radiopharmaceutical group, one of the largest in nuclear medicine, supplying SPECT and PET isotopes and generators and developing 177Lu-PSMA-I&T as a competitor to Pluvicto in prostate cancer. Its ECLIPSE phase 3 trial of 177Lu-PSMA-I&T met its radiographic progression-free survival endpoint in taxane-naive metastatic castration-resistant prostate cancer, a Japanese registrational trial with PeptiDream and PDRadiopharma enrolled its first patient in February 2026, and the regulatory submission plan is under discussion with the FDA. Nuclide links it to DOTATATE imaging agents, samarium-153 lexidronam, radionuclide generators and the therapeutic isotope supply chain. Whether a second lutetium PSMA agent can differentiate on supply and price rather than efficacy is the open question. The manufacturing cost of radioactive medicines is the bottleneck it bears on.","asOf":"2026-09-06","links":[{"label":"Official website","url":"https://www.curiumpharma.com"}],"tags":[],"related":["lu-177","sm-153"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["lu177-psma-it"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06235151"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Paris","country":"FR","companyType":"radiopharma","website":"https://www.curiumpharma.com","investors":[],"funding":[],"route":"/companies/curium/"}
{"id":"eckert-ziegler","kind":"company","name":"Eckert & Ziegler","aka":[],"tldr":"German isotope and radiopharmaceutical services company supplying Lu-177, Ga-68 generators, Ac-225 development, and contract manufacturing.","summary":"Eckert and Ziegler, based in Berlin and listed as EUZ.DE, is a German isotope and radiopharmaceutical services company supplying lutetium-177, gallium-68 generators, actinium-225 development and contract manufacturing. It makes the GalliaPharm gallium-68 generator and non-carrier-added lutetium-177, sold as Theralugand, runs actinium-225 production projects and offers CDMO services to radioligand developers. Nuclide links it to the therapeutic isotope supply chain, radiopharmacy and cyclotron networks and radionuclide generators and cold kits. Whether generator-based gallium-68 keeps its place as cyclotron production and fluorine-18 tracers spread is the open question. The isotope supply chain page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.ezag.com"}],"tags":["supporting"],"related":["f-18","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain","radiopharmacy-network"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Berlin","country":"DE","companyType":"radiopharma","website":"https://www.ezag.com","ticker":"EUZ.DE","investors":[],"funding":[],"route":"/companies/eckert-ziegler/"}
{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","aka":[],"tldr":"Eli Lilly makes Verzenio and Retevmo, as well as the oral SERD imlunestrant and the BTK inhibitor pirtobrutinib.","summary":"Eli Lilly, based in Indianapolis and listed as LLY, makes Verzenio and Retevmo, the oral SERD imlunestrant and the BTK inhibitor pirtobrutinib, and its oncology unit includes Loxo Oncology. The portfolio spans abemaciclib, selpercatinib, imlunestrant, sold as Inluriyo from 2025, pirtobrutinib, olomorasib against KRAS G12C, a PI3K-alpha mutant-selective programme from Scorpion, and older products including cetuximab, gemcitabine and necitumumab. Nuclide links it to the monarchE paper on two years of adjuvant abemaciclib, to CLEAR in kidney cancer, to GLP-1 receptor agonists and obesity-related cancer risk, to ideas for trials of GLP-1 drugs with cancer as the primary outcome, and to partners including Isomorphic Labs and Innovent. Whether Lilly's GLP-1 franchise becomes an oncology story is the question its idea links raise. Abemaciclib and selpercatinib have their own pages.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.lilly.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["point-biopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Indianapolis, IN","country":"US","companyType":"pharma","website":"https://www.lilly.com","ticker":"LLY","investors":[],"funding":[],"route":"/companies/eli-lilly/"}
{"id":"evergreen-theragnostics","kind":"company","name":"Evergreen Theragnostics","aka":[],"tldr":"Evergreen Theragnostics manufactures radioactive cancer medicines for other companies and develops its own imaging agent for neuroendocrine tumours and a treatment for small cell lung cancer. Lantheus agreed to buy it in 2025.","summary":"Evergreen Theragnostics is a Springfield, New Jersey radiopharmaceutical company combining contract development and manufacturing (CDMO) services with proprietary products. Its facility, completed in October 2021, has produced clinical material for partners including Clovis Oncology (225Ac FAP-2286), Clarity (copper theranostics), MTTI and Precirix (CAM-H2). Proprietary programmes include OCTEVY, a registrational-stage PET diagnostic for neuroendocrine tumours, and EVG321, a CCK2 receptor-targeted radioligand licensed from the Medical University of Innsbruck in May 2024 for small cell lung cancer, with the CCK2-VIEW phase 2 trial opened in the EU in October 2024. In January 2025 Lantheus agreed to acquire Evergreen for USD 250 million upfront and up to USD 752.5 million in milestones, to become a fully integrated radiopharmaceutical company.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.evergreentgn.com/"},{"label":"Lantheus acquisition release","url":"https://www.evergreentgn.com/2025/01/28/lantheus-to-acquire-evergreen-theragnostics-for-upfront-payment-of-250-million-to-drive-strategic-evolution-into-fully-integrated-radiopharmaceutical-leader/"},{"label":"News","url":"https://www.evergreentgn.com/news/"}],"tags":[],"related":["ac-225"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":["radioligand-therapy","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Venture financing before the acquisition not fetched and omitted. Completion of the Lantheus deal not confirmed from a fetched page, although the company site now links to Lantheus careers and pipeline."],"hq":"Springfield, NJ","country":"US","companyType":"radiopharma","website":"https://www.evergreentgn.com/","stage":"acquired","investors":[],"funding":[{"round":"Acquisition","year":2025,"amountUsd":250000000,"source":"https://www.evergreentgn.com/2025/01/28/lantheus-to-acquire-evergreen-theragnostics-for-upfront-payment-of-250-million-to-drive-strategic-evolution-into-fully-integrated-radiopharmaceutical-leader/","note":"USD 250 million upfront plus up to USD 752.5 million in milestones; all-cash, announced 28 January 2025"}],"acquiredBy":"lantheus","route":"/companies/evergreen-theragnostics/"}
{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","aka":[],"tldr":"Alpha-emitter company acquired by AstraZeneca ($2.4B, 2024); FPI-2265 (225Ac-PSMA-I&T) in phase 3.","summary":"Fusion Pharmaceuticals, based in Hamilton, Ontario, is the alpha-emitter company acquired by AstraZeneca for 2.4 billion dollars in 2024, and its FPI-2265, an actinium-225 PSMA-I&T agent, is in phase 3. Its pipeline also includes FPI-2068, an EGFR by c-MET bispecific radioconjugate, and the company holds actinium-225 supply agreements. Nuclide links it to the AlphaBreak trial of FPI-2265 and the AcTION trial of 225Ac-PSMA-617, to targeted alpha therapy, to the actinium-225 PSMA agents record and to the radiopharmaceutical roadmap. Whether actinium PSMA therapy can improve on lutetium PSMA therapy is the question AlphaBreak will answer. Actinium-225 PSMA agents have their own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.astrazeneca.com"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["ac225-psma"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Hamilton, ON","country":"CA","companyType":"radiopharma","website":"https://www.astrazeneca.com","investors":[],"funding":[],"route":"/companies/fusion-pharma/"}
{"id":"futurechem","kind":"company","name":"FutureChem","aka":[],"tldr":"FutureChem is a South Korea-based radiopharmaceutical company running 2 late-stage cancer trials of [F-18]Florastamin in prostate cancer.","summary":"FutureChem, based in Seoul, South Korea, is a radiopharmaceutical company. FUTURECHEM is a radiopharmaceutical drug-development company specialising in PET diagnostic imaging agents for neurological and oncological conditions. On ClinicalTrials.gov it is the lead sponsor of 2 recruiting or active phase 2 and phase 3 interventional cancer trials (2 in phase 3), testing [F-18]Florastamin in prostate cancer. The largest, NCT05004285 (Evaluate the Clinical Usefulness of [F-18]Florastamin PET/CT Imaging Diagnosis Compared to MRI Diagnosis), plans to enrol 398 participants. Sponsor and trial facts are from the ClinicalTrials.gov registry; company facts are from the official website.","asOf":"2026-09-11","links":[{"label":"Official website","url":"https://www.futurechem.co.kr"},{"label":"ClinicalTrials.gov: trials led by FutureChem","url":"https://clinicaltrials.gov/search?lead=FutureChem"}],"tags":["ctgov-sponsor"],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Seoul","country":"KR","companyType":"radiopharma","website":"https://www.futurechem.co.kr","stage":"public","investors":[],"funding":[],"route":"/companies/futurechem/"}
{"id":"ge-healthcare","kind":"company","name":"GE HealthCare","aka":[],"tldr":"GE HealthCare, of Chicago, makes PET/CT, MRI and CT scanners (Omni Legend, SIGNA, Revolution) and PET tracers through its Pharmaceutical Diagnostics business, including Cerianna, the fluoroestradiol F-18 agent that images oestrogen receptors in breast cancer. Whether receptor-imaging tracers change treatment decisions often enough to be reimbursed is its tracer business's open question.","summary":"GE HealthCare, based in Chicago and listed as GEHC, makes PET/CT, MRI and CT scanners and PET tracers through its Pharmaceutical Diagnostics business. Its scanners include the Omni Legend PET/CT, SIGNA MRI and Revolution CT, and its tracer business spans flurpiridaz, cyclotrons and Cerianna, the fluoroestradiol F-18 agent for imaging oestrogen receptor expression in breast cancer. Nuclide links it to PET/CT, MRI and CT, to medical cyclotrons and total-body PET hardware, and to the fluoroestradiol F-18 drug record. Whether receptor-imaging tracers such as FES change treatment decisions often enough to be reimbursed widely is the open question for its tracer business. Fluoroestradiol F-18 has its own page.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/GE_HealthCare","links":[{"label":"Official website","url":"https://www.gehealthcare.com"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet-ct","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07219238"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Chicago, IL","country":"US","companyType":"imaging","website":"https://www.gehealthcare.com","ticker":"GEHC","investors":[],"funding":[],"route":"/companies/ge-healthcare/"}
{"id":"hamamatsu","kind":"company","name":"Hamamatsu Photonics","aka":[],"tldr":"Hamamatsu is the photonics company behind the NanoZoomer slide scanners and the photodetectors inside most PET scanners.","summary":"Hamamatsu Photonics, based in Hamamatsu, Japan, and listed as 6965.T, is the photonics company behind the NanoZoomer slide scanners and the photodetectors inside most PET scanners. Its NanoZoomer S360 and S60 whole-slide scanners serve digital pathology, and its silicon photomultipliers and photomultiplier tubes sit inside PET/CT and SPECT systems from many manufacturers. Nuclide links it to whole-slide scanners and image management and to nuclear medicine and total-body PET hardware. Its position as a component supplier means that advances in detector sensitivity reach the whole imaging market through it. Whether that quiet role is recognised when total-body PET costs are debated is the fair question.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hamamatsu_Photonics","links":[{"label":"Official website","url":"https://www.hamamatsu.com"}],"tags":["supporting"],"related":[],"indications":[],"sections":[],"technologies":["nuclear-medicine-hardware"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Hamamatsu","country":"JP","companyType":"imaging","website":"https://www.hamamatsu.com","ticker":"6965.T","investors":[],"funding":[],"route":"/companies/hamamatsu/"}
{"id":"iba","kind":"company","name":"IBA (Ion Beam Applications)","aka":[],"tldr":"IBA (Ion Beam Applications), of Louvain-la-Neuve, Belgium, is the largest supplier of proton therapy equipment: its Proteus One and Proteus Plus systems equip proton centres worldwide, and it also builds cyclotrons for PET isotope production. Proton therapy's capital cost is the problem its compact systems try to answer.","summary":"IBA, Ion Beam Applications, based in Louvain-la-Neuve in Belgium, is the largest supplier of proton therapy equipment. Its Proteus One and Proteus Plus systems equip proton centres worldwide, and it also makes cyclotrons for PET isotope production and supports actinium-225 research. Nuclide links it to proton therapy and proton arc therapy, to medical cyclotrons and synthesis modules, to centres including Centre Antoine Lacassagne, Uppsala, UZ Leuven and the West German Cancer Center in Essen, and to ideas such as compact FLASH and proton systems at the price of a conventional linac and pooled coverage-with-evidence for proton therapy across all centres. Whether proton therapy can be made cheap enough to be judged on evidence rather than capital cost is the open question its compact systems address. The proton therapy page carries the trial detail.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.iba-worldwide.com"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Louvain-la-Neuve","country":"BE","companyType":"devices","website":"https://www.iba-worldwide.com","investors":[],"funding":[],"route":"/companies/iba/"}
{"id":"ire","kind":"company","name":"IRE (Institut national des Radioéléments)","aka":["IRE ELiT"],"tldr":"IRE in Belgium is one of the world's few molybdenum-99 processors, taking irradiated targets from European research reactors, and its IRE ELiT arm makes the Galli Eo gallium-68 generator.","summary":"The Institut national des Radioéléments at Fleurus processes uranium targets irradiated in BR2, the Petten High Flux Reactor, MARIA and LVR-15 into molybdenum-99 and iodine-131 for generator and radiopharmaceutical makers. Its subsidiary IRE ELiT produces the Galli Eo germanium-68/gallium-68 generator used for PSMA and somatostatin PET and non-carrier-added lutetium-177. It is a Belgian public-interest foundation rather than a listed company.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.ire.eu"}],"tags":["manufacturing-wave"],"related":["ga-68","mo-99","ge-68","lu-177","i-131"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","cyclotron-isotope-production","radionuclide-generators-kits","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Fleurus","country":"BE","companyType":"radiopharma","website":"https://www.ire.eu","founded":1971,"stage":"private-large","investors":[],"funding":[],"route":"/companies/ire/"}
{"id":"isotopia","kind":"company","name":"Isotopia Molecular Imaging","aka":[],"tldr":"Isotopia is an Israeli producer of non-carrier-added lutetium-177 and PET tracers that supplies several radioligand developers.","summary":"Isotopia Molecular Imaging produces non-carrier-added lutetium-177 by separating it from irradiated ytterbium-176, and manufactures PET radiopharmaceuticals for Israeli hospitals. It has supply agreements with a number of companies developing lutetium-based radioligands and is one of the independent lutetium sources that grew as demand rose after lutetium-177 vipivotide tetraxetan was approved.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.isotopia.co.il"}],"tags":["manufacturing-wave"],"related":["lu-177"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Petah Tikva","country":"IL","companyType":"radiopharma","website":"https://www.isotopia.co.il","stage":"growth","investors":[],"funding":[],"route":"/companies/isotopia/"}
{"id":"itm","kind":"company","name":"ITM Isotope Technologies Munich","aka":["ITM Solucin GmbH"],"tldr":"ITM is the largest non-carrier-added lutetium-177 supplier and the developer of ITM-11 (177Lu-edotreotide).","summary":"ITM Isotope Technologies Munich is the largest supplier of non-carrier-added lutetium-177, sold as EndolucinBeta, and the developer of ITM-11, or 177Lu-edotreotide. ITM-11 was positive in the COMPETE phase 3 trial in gastroenteropancreatic neuroendocrine tumours in 2025, and the company is investing in actinium-225 supply. Nuclide links it to neuroendocrine tumours, to somatostatin receptor 2 as a target, to peptide receptor radionuclide therapy and the therapeutic isotope supply chain, to the radiopharmaceutical roadmap, and to the idea of building Western ytterbium-176 enrichment so lutetium-177 has more than one supplier. Manufacturing cost and time for radioactive medicines is the bottleneck it sits inside. Whether a supplier can also succeed as a drug developer is the open question.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://itm-radiopharma.com"}],"tags":[],"related":["lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04919226"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Munich","country":"DE","companyType":"radiopharma","website":"https://itm-radiopharma.com","investors":[],"funding":[],"route":"/companies/itm/"}
{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","aka":["Alza Corporation","Janssen","Ortho Biotech Products, L.P.","Ortho Biotech","Sequus Pharmaceuticals","Centocor, Inc.","Centocor","Alza Corporation, DE, USA","Cougar Biotechnology, Inc.","Cougar Biotechnology","McNeil Consumer & Specialty Pharmaceuticals","McNeil"],"tldr":"Johnson & Johnson leads in multiple myeloma (Darzalex, Carvykti, Tecvayli, Talvey) and in bispecific antibodies for lung cancer (Rybrevant).","summary":"Johnson & Johnson, based in New Brunswick, New Jersey, and listed as JNJ, leads in multiple myeloma with Darzalex, Carvykti, Tecvayli and Talvey and in bispecific antibodies for lung cancer with Rybrevant. Its oncology portfolio spans daratumumab, teclistamab, talquetamab, ciltacabtagene autoleucel developed with Legend, amivantamab with lazertinib, abiraterone and apalutamide in prostate cancer, TAR-200 intravesical gemcitabine for bladder cancer approved in 2025, and pasritamig, a KLK2 by CD3 bispecific. Nuclide links it to the CARTITUDE-1 and CARTITUDE-4, MAIA, CEPHEUS and MajesTEC-1 papers, to the LEGEND-2 trial, to robotic bronchoscopy, and to the Yale Open Data Access project. Whether CAR-T and bispecifics move into first-line myeloma and displace daratumumab combinations is the question its own portfolio poses. Teclistamab, cilta-cel and amivantamab have their own pages.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Johnson_%26_Johnson","links":[{"label":"Official website","url":"https://www.jnj.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["jnj-87189401"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04557059"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"New Brunswick, NJ","country":"US","companyType":"pharma","website":"https://www.jnj.com","ticker":"JNJ","investors":[],"funding":[],"route":"/companies/johnson-johnson/"}
{"id":"jubilant-radiopharma","kind":"company","name":"Jubilant Radiopharma","aka":[],"tldr":"Jubilant Radiopharma is a radiopharmacy network and the manufacturer of I-131 MIBG (AdreView), Ruby-Fill, and PET tracers.","summary":"Jubilant Radiopharma, based in Yardley, Pennsylvania, is a radiopharmacy network and the manufacturer of iodine-131 MIBG, sold as AdreView, Ruby-Fill and PET tracers. It is part of India's Jubilant Pharmova and combines US radiopharmacies with a radiopharmaceutical manufacturing business. Nuclide links it to radiopharmacy and cyclotron networks and PET tracer manufacturing and distribution, and to Syngene International as a related company. Whether an Indian-owned network can expand from established diagnostic products into the therapeutic radioligand market is the open question. The radiopharmacy technology page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.jubilantradiopharma.com"}],"tags":["supporting"],"related":["i-131"],"indications":[],"sections":[],"technologies":["radiopharmacy-network","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Yardley, PA","country":"US","companyType":"radiopharma","website":"https://www.jubilantradiopharma.com","investors":[],"funding":[],"route":"/companies/jubilant-radiopharma/"}
{"id":"lantheus","kind":"company","name":"Lantheus","aka":["Progenics Pharmaceuticals, Inc.","Progenics","Molecular Insight Pharmaceuticals, Inc.","Molecular Insight Pharmaceuticals"],"tldr":"Lantheus makes Pylarify, the leading PSMA PET agent, with a new TruVu formulation approved in March 2026.","summary":"Lantheus, based in Bedford, Massachusetts, and listed as LNTH, makes Pylarify, or piflufolastat F-18, the leading PSMA PET agent, with a new TruVu formulation approved in March 2026. Its portfolio also includes Neuraceq for amyloid imaging, PNT2002, a 177Lu-PSMA-I&T therapy whose SPLASH phase 3 missed overall survival, and PNT2003, a generic 177Lu-DOTATATE, and Nuclide also links it to iobenguane I-131 and samarium-153 lexidronam. It connects to prostate cancer, to PET tracer manufacturing and distribution and radionuclide generators, and to Evergreen Theragnostics. Whether an imaging leader can become a therapy company after SPLASH is the open question. Piflufolastat F-18 has its own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.lantheus.com"}],"tags":[],"related":["f-18","lu-177","i-131","sm-153"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["pylarify","i131-mibg"],"companies":["evergreen-theragnostics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06298916","nct07357519"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Bedford, MA","country":"US","companyType":"radiopharma","website":"https://www.lantheus.com","ticker":"LNTH","investors":[],"funding":[],"route":"/companies/lantheus/"}
{"id":"mariana-oncology","kind":"company","name":"Mariana Oncology","aka":[],"tldr":"Mariana Oncology designs small protein fragments that carry a radioactive isotope to tumours, starting with small cell lung cancer. Novartis bought the company in 2024 for 1 billion dollars up front.","summary":"Mariana Oncology, founded in 2021 in Watertown, Massachusetts by Atlas Venture, Access Biotechnology and RA Capital Management, built a fully integrated radiopharmaceutical platform combining peptide discovery, radiochemistry, in-house GMP manufacturing, isotope supply and formulations to extend product shelf life. Its portfolio of peptide-based radioligand therapies addresses a range of solid tumours; the lead candidate MC-339 is a radioligand therapy for small cell lung cancer that was expected to enter the clinic in 2024. The company closed a USD 175 million Series B in September 2023 co-led by Deep Track Capital and Forbion, and in May 2024 agreed to be acquired by Novartis for USD 1 billion upfront and up to USD 750 million in milestones. As a Novartis company it announced a USD 50 million expansion of radioligand R&D facilities in June 2025.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://marianaoncology.com/"},{"label":"Series B press release","url":"https://marianaoncology.com/news/mariana-oncology-announces-usd175-million-series-b-financing/"},{"label":"Novartis acquisition announcement","url":"https://marianaoncology.com/news/mariana-oncology-to-be-acquired-by-novartis-to-advance-precision-radiopharmaceuticals-to-treat-cancer/"}],"tags":[],"related":[],"indications":["sclc"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["MC-339 target not stated on fetched pages. Series A not fetched and omitted."],"hq":"Watertown, MA","country":"US","companyType":"radiopharma","website":"https://marianaoncology.com/","founded":2021,"stage":"acquired","investors":[],"funding":[{"round":"Series B","year":2023,"amountUsd":175000000,"source":"https://marianaoncology.com/news/mariana-oncology-announces-usd175-million-series-b-financing/"},{"round":"Acquisition","year":2024,"amountUsd":1000000000,"source":"https://marianaoncology.com/news/mariana-oncology-to-be-acquired-by-novartis-to-advance-precision-radiopharmaceuticals-to-treat-cancer/","note":"USD 1 billion upfront plus up to USD 750 million in milestones"}],"acquiredBy":"novartis","route":"/companies/mariana-oncology/"}
{"id":"mediso","kind":"company","name":"Mediso","aka":[],"tldr":"Mediso is a Hungarian nuclear medicine company making AnyScan SPECT/CT and PET/CT cameras for hospitals and nanoScan PET/MRI and SPECT/CT scanners for preclinical research.","summary":"Founded in Budapest in 1990, Mediso is one of the few independent makers of clinical gamma cameras and SPECT/CT systems (the AnyScan family, including combined SPECT/CT/PET) and is a leader in small-animal imaging with the nanoScan PET/MRI, PET/CT and SPECT/CT systems used in radiopharmaceutical development. Nuclide links it to SPECT/CT and SPECT.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Mediso","links":[{"label":"Official website","url":"https://mediso.com"}],"tags":["machines-wave"],"related":[],"indications":[],"sections":[],"technologies":["spect-ct","spect","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Budapest","country":"HU","companyType":"imaging","website":"https://mediso.com","founded":1990,"stage":"growth","investors":[],"funding":[],"route":"/companies/mediso/"}
{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","aka":[],"tldr":"Merck & Co. (MSD) makes Keytruda, the world's best-selling cancer drug, and is now building the next act around TROP2 ADCs and personalised vaccines.","summary":"Pembrolizumab anchors >40 indications. Post-2028 patent-cliff strategy: sacituzumab tirumotecan (Kelun licence, >10 phase 3 trials), ifinatamab/patritumab/raludotatug deruxtecan (Daiichi Sankyo alliance, up to $22B), intismeran autogene (Moderna), zilovertamab vedotin, belzutifan, and a PD-1×VEGF bispecific (LaNova).","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.merck.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","olaparib","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Rahway, NJ","country":"US","companyType":"pharma","website":"https://www.merck.com","ticker":"MRK","investors":[],"funding":[],"route":"/companies/merck/"}
{"id":"mim-software","kind":"company","name":"MIM Software (GE HealthCare)","aka":[],"tldr":"Contouring, image fusion, and dosimetry software (MIM Maestro, SurePlan) for radiotherapy and radioligand therapy, acquired by GE HealthCare in 2024.","summary":"MIM Software, based in Cleveland and acquired by GE HealthCare in 2024, makes contouring, image fusion and dosimetry software, including MIM Maestro and SurePlan, for radiotherapy and radioligand therapy. Its Contour ProtégéAI performs auto-contouring, its PET/CT fusion supports planning, and its personalised dosimetry serves lutetium-177 and yttrium-90 therapies. Nuclide links it to AI auto-contouring and adaptive planning, SPECT and bone scan imaging, and radioligand therapy with beta emitters. Whether personalised dosimetry becomes standard for radioligand therapy, rather than fixed dosing, is the open question its tools are built for. The radioligand therapy page carries the wider evidence.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.mimsoftware.com"}],"tags":["supporting"],"related":["lu-177","y-90"],"indications":[],"sections":[],"technologies":["spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Cleveland, OH","country":"US","companyType":"ai-software","website":"https://www.mimsoftware.com","investors":[],"funding":[],"route":"/companies/mim-software/"}
{"id":"monopar","kind":"company","name":"Monopar Therapeutics","aka":["Monopar Therapeutics Inc.","Monopar"],"tldr":"Monopar is a Chicago-area biotech that took the mucositis drug validive into a phase 3 trial in head and neck cancer, which failed in 2023, and now develops radiopharmaceuticals against the uPAR protein.","summary":"Monopar Therapeutics, based in the Chicago area, developed validive (clonidine mucobuccal tablet) to prevent severe oral mucositis in patients having chemoradiotherapy for oropharyngeal cancer; the phase 3 VOICE trial did not meet its endpoint in 2023. The company has since focused on MNPR-101, an antibody against the urokinase receptor uPAR, as an imaging agent and radiotherapeutic, and on a Wilson disease programme. Its trials are registered on ClinicalTrials.gov under Monopar as lead sponsor.","asOf":"2026-09-11","links":[{"label":"Official website","url":"https://www.monopartx.com"},{"label":"ClinicalTrials.gov: trials led by Monopar Therapeutics Inc.","url":"https://clinicaltrials.gov/search?lead=Monopar%20Therapeutics%20Inc."}],"tags":["ctgov-sponsor"],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Chicago, IL","country":"US","companyType":"biotech","website":"https://www.monopartx.com","stage":"public","investors":[],"funding":[],"route":"/companies/monopar/"}
{"id":"navidea","kind":"company","name":"Navidea Biopharmaceuticals","aka":["Navidea","Neoprobe Corporation"],"tldr":"Navidea developed technetium-99m tilmanocept (Lymphoseek), the radiotracer approved in 2013 for mapping sentinel lymph nodes in breast cancer, melanoma and head and neck cancer.","summary":"Navidea Biopharmaceuticals, based in Dublin, Ohio and formerly Neoprobe, developed technetium Tc-99m tilmanocept (Lymphoseek), a receptor-targeted radiotracer that binds CD206 on macrophages in lymph nodes; the FDA approved it in 2013 for sentinel lymph node mapping in breast cancer and melanoma and in 2014 for oral cavity squamous cell carcinoma. The company sold North American rights to Cardinal Health in 2017 and later focused on macrophage imaging in rheumatoid arthritis; its listing was delisted in 2023. It appears on Nuclide as a lead sponsor of phase 3 cancer trials on ClinicalTrials.gov.","asOf":"2026-09-11","wikipedia":"https://en.wikipedia.org/wiki/Navidea_Biopharmaceuticals","links":[{"label":"ClinicalTrials.gov: trials led by Navidea Biopharmaceuticals","url":"https://clinicaltrials.gov/search?lead=Navidea%20Biopharmaceuticals"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Navidea_Biopharmaceuticals"}],"tags":["ctgov-sponsor"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["tilmanocept-tc99m"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Dublin, OH","country":"US","companyType":"diagnostics","website":"https://www.navidea.com","stage":"public","investors":[],"funding":[],"route":"/companies/navidea/"}
{"id":"nordion","kind":"company","name":"Nordion (Sotera Health)","aka":[],"tldr":"Nordion supplies most of the world's cobalt-60, which sterilises single-use bioprocess bags and medical devices and powers Gamma Knife units, and was the largest molybdenum-99 processor until Canada's NRU reactor stopped.","summary":"Nordion, an Ottawa company owned by Sotera Health, sells cobalt-60 sources harvested from Canadian CANDU power reactors operated by Bruce Power and Ontario Power Generation, used for gamma sterilisation of medical products and single-use bioprocess consumables and for Gamma Knife radiosurgery. Until the NRU reactor at Chalk River ceased isotope production in 2016 it processed a large share of the world's molybdenum-99, and its exit reshaped the supply chain described in the reactor record.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.nordion.com"}],"tags":["manufacturing-wave"],"related":["mo-99"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Ottawa","country":"CA","companyType":"radiopharma","website":"https://www.nordion.com","stage":"public","investors":[],"funding":[],"route":"/companies/nordion/"}
{"id":"northstar-medical-radioisotopes","kind":"company","name":"NorthStar Medical Radioisotopes","aka":[],"tldr":"NorthStar is a non-reactor producer of Mo-99 in the US and an emerging supplier of non-carrier-added Lu-177 and Ac-225 made with electron accelerators.","summary":"NorthStar Medical Radioisotopes, based in Beloit, Wisconsin, is a non-reactor producer of molybdenum-99 in the United States and an emerging supplier of non-carrier-added lutetium-177 and actinium-225 made with electron accelerators. Its RadioGenix Mo-99 system was approved in 2018, its accelerator-based actinium-225 production facility came online in 2024 to 2025, and it holds lutetium-177 supply agreements. Nuclide links it to the therapeutic isotope supply chain for Mo-99, Lu-177 and Ac-225. Whether accelerator production can supply actinium-225 at the volumes the alpha therapies in phase 3 will need is the open question. The isotope supply chain page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.northstarnm.com"}],"tags":["supporting"],"related":["mo-99","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Beloit, WI","country":"US","companyType":"radiopharma","website":"https://www.northstarnm.com","investors":[],"funding":[],"route":"/companies/northstar-medical-radioisotopes/"}
{"id":"novartis","kind":"company","name":"Novartis","aka":["Endocyte"],"tldr":"The company that made radioligand therapy a business, with Pluvicto and Lutathera, and the maker of Kisqali and Gleevec.","summary":"Novartis, based in Basel and listed as NOVN.SW, is the company that made radioligand therapy a business with Pluvicto and Lutathera, and the maker of Kisqali, Gleevec, Scemblix and Kymriah, the first approved CAR-T. Pluvicto sells more than 1.5 billion dollars a year, and the pipeline includes actinium-225 PSMA-617, FAP-2286 and the Mariana Oncology acquisition, alongside adjuvant ribociclib, imatinib and asciminib. Nuclide links it to the first imatinib trial and IRIS, to ELIANA and JULIET for tisagenlecleucel, to peptide receptor radionuclide therapy, to the AlphaBreak and AcTION actinium trials, and to ideas on Western ytterbium-176 enrichment and two-day CAR-T manufacture. Manufacturing cost and time for living and radioactive medicines is the bottleneck its two flagship modalities share. Lutetium-177 vipivotide tetraxetan and lutetium-177 dotatate have their own pages.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Novartis","links":[{"label":"Official website","url":"https://www.novartis.com"}],"tags":[],"related":["lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto","lutathera","ac225-psma","fap-2286","aaa817"],"companies":["mariana-oncology"],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1","nct05939414","nct04711135","nct06894511","nct06004661","nct05142696"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Basel","country":"CH","companyType":"pharma","website":"https://www.novartis.com","ticker":"NOVN.SW","investors":[],"funding":[],"route":"/companies/novartis/"}
{"id":"ntp-radioisotopes","kind":"company","name":"NTP Radioisotopes","aka":["NTP"],"tldr":"NTP, part of South Africa's state nuclear corporation, processes molybdenum-99 and other isotopes from the SAFARI-1 reactor and was the first major producer to switch to low-enriched uranium targets.","summary":"NTP Radioisotopes, a subsidiary of the South African Nuclear Energy Corporation, irradiates targets in the SAFARI-1 research reactor at Pelindaba and processes molybdenum-99, iodine-131 and lutetium-177 for export to generator makers and radiopharmacies worldwide. It converted its molybdenum production to low-enriched uranium targets ahead of other producers. Regulator-ordered shutdowns of its processing facility in 2017 and 2018 removed a large share of world molybdenum-99 supply for months and showed how few processors there are.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.ntp.co.za"}],"tags":["manufacturing-wave"],"related":["mo-99","lu-177","i-131"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Pelindaba, near Pretoria","country":"ZA","companyType":"radiopharma","website":"https://www.ntp.co.za","stage":"private-large","investors":[],"funding":[],"route":"/companies/ntp-radioisotopes/"}
{"id":"nucleus-radiopharma","kind":"company","name":"Nucleus RadioPharma","aka":[],"tldr":"Nucleus RadioPharma does not make its own cancer drugs; it manufactures and ships radioactive cancer medicines for other companies, which is hard because the drugs decay within days. It is expanding its plants in Minnesota and Pennsylvania.","summary":"Nucleus RadioPharma is a Rochester, Minnesota contract development and manufacturing organisation (CDMO) dedicated to targeted radiotherapies, offering formulation and analytical development, isotope-flexible supply chain, GMP manufacturing and regulatory support. Its Rochester facility can produce around 50,000 patient doses per year and a 47,000 square foot Spring House, Pennsylvania site is planned to open in 2028. Customers include Clarity Pharmaceuticals, with a commercial manufacturing agreement for 64Cu-SAR-bisPSMA signed in April 2026, and the company has a Thermo Fisher Scientific alliance and a BWXT Medical isotope supply agreement (June 2026). Former FDA Commissioner Stephen Hahn became CEO in August 2025. In April 2026 the company secured USD 50 million from OrbiMed to expand manufacturing capacity; earlier backers listed in partner releases include Eclipse, Mayo Clinic, AstraZeneca and GE HealthCare.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://nucleusrad.com/"},{"label":"OrbiMed financing release (PDF)","url":"https://nucleusrad.com/wp-content/uploads/Nucleus-RadioPharma-Secures-50-Million-Financing-from-OrbiMed-to-Expand-Radiopharmaceutical-Manufacturing-Capacity.pdf"},{"label":"News and events","url":"https://nucleusrad.com/news-events/"}],"tags":[],"related":["cu-64"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Not a therapeutics developer; companyType set to cro-services. Backer list other than OrbiMed comes from the 'About Nucleus RadioPharma' boilerplate in a Clarity Pharmaceuticals PR Newswire release. Founding (2022, Eclipse and Mayo Clinic) and earlier financing not fetched from a primary page; the old domain nucleusradiopharma.com is for sale."],"hq":"Rochester, MN","country":"US","companyType":"cro-services","website":"https://nucleusrad.com/","stage":"startup","investors":[],"funding":[{"round":"Series B","year":2026,"amountUsd":50000000,"source":"https://nucleusrad.com/wp-content/uploads/Nucleus-RadioPharma-Secures-50-Million-Financing-from-OrbiMed-to-Expand-Radiopharmaceutical-Manufacturing-Capacity.pdf","note":"USD 50 million financing from OrbiMed announced 20 April 2026; the company did not name the round, labelled Series B here for schema purposes only"}],"route":"/companies/nucleus-radiopharma/"}
{"id":"nusano","kind":"company","name":"Nusano","aka":[],"tldr":"Nusano is a Utah company building an isotope production plant around its own ion beam technology, aiming at actinium-225 and other therapeutic isotopes that are in short supply.","summary":"Nusano has developed an ion source and accelerator platform intended to produce a range of medical isotopes at commercial scale and is building a production facility in West Valley City, Utah. Its announced targets include actinium-225 and other alpha and beta emitters for radioligand therapy, and it has signed supply agreements with radiopharmaceutical developers. It is privately funded.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://www.nusano.com"}],"tags":["manufacturing-wave"],"related":["ac-225"],"indications":[],"sections":[],"technologies":["actinium-225-supply","cyclotron-isotope-production","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"West Valley City, Utah","country":"US","companyType":"radiopharma","website":"https://www.nusano.com","stage":"growth","investors":[],"funding":[],"route":"/companies/nusano/"}
{"id":"orano-med","kind":"company","name":"Orano Med","aka":[],"tldr":"Orano Med is the leading lead-212 producer and the developer of 212Pb-DOTAMTATE (AlphaMedix).","summary":"Orano Med, based in Paris and Plano, Texas, is the leading producer of lead-212 and the developer of 212Pb-DOTAMTATE, known as AlphaMedix, an alpha-emitting radioligand for somatostatin-receptor-positive neuroendocrine tumours. AlphaMedix reported a 56 percent objective response rate in its phase 2, the company builds lead-212 generators, and it works with Sanofi and RadioMedix. Nuclide links it to neuroendocrine tumours, to somatostatin receptor 2 as a target, to peptide receptor radionuclide therapy, targeted alpha therapy and the isotope supply chain, and to the idea of funding alpha emitters beyond actinium-225, including lead-212, terbium-149 and astatine-211. Manufacturing cost and time for radioactive medicines is the bottleneck it sits inside. Whether lead-212 can be delivered to enough hospitals to matter is the open question.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.oranomed.com"}],"tags":[],"related":["ac-225","pb-212","at-211"],"indications":[],"sections":[],"technologies":[],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07278479"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Paris / Plano, TX","country":"FR","companyType":"radiopharma","website":"https://www.oranomed.com","investors":[],"funding":[],"route":"/companies/orano-med/"}
{"id":"perspective-therapeutics","kind":"company","name":"Perspective Therapeutics","aka":[],"tldr":"Lead-212 alpha-therapy company whose SSTR2 agent [212Pb]VMT-α-NET reported a 43% response rate in neuroendocrine tumours and is heading for phase 3.","summary":"Phase 1/2a of [212Pb]VMT-α-NET (NCT05636618): 43% ORR in cohort 2 with 72% progression-free/alive at the 2026 update; 76 NET patients treated by July 2026; first meningioma patient dosed June 2026; EU orphan designation July 2026. Phase 3 planned at a cumulative 20 mCi dose. Also developing PSMA and melanocortin-1 receptor 212Pb agents. Its FAP-alpha agent PSV359, paired with the 203Pb/68Ga imaging analogue PSV377, is in a phase 1/2 first-in-human study (NCT06710756); on 14 September 2026 the company announced a collaboration and supply agreement with Merck to add cohorts combining [212Pb]PSV359 with pembrolizumab in FAP-alpha-positive non-small cell lung cancer and colorectal cancer, which is the first time an alpha-emitting radioligand has been taken into NSCLC. The dose-expansion part of the VMT-alpha-NET trial also enrols bronchial neuroendocrine tumours.","asOf":"2026-09-04","links":[{"label":"Q2 2026 highlights","url":"https://www.globenewswire.com/news-release/2026/08/10/3342260/0/en/perspective-therapeutics-provides-recent-business-highlights-and-reports-2q-2026-results.html"},{"label":"Clinical collaboration and supply agreement with Merck to evaluate [212Pb]PSV359 with Keytruda in FAP-alpha positive solid tumours, including NSCLC (14 September 2026)","url":"https://www.perspectivetherapeutics.com/pr/perspective-therapeutics-announces-clinical-collaboration-and-supply-agreement-with-merck-to-evaluate-212pbpsv359-in-combination-with-keytruda-pembrolizumab-in-fap-a-positive-solid-tumors"}],"tags":[],"related":["nsclc","lung-net","ga-68","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["sstr2","psma"],"drugs":["pb-212-vmt-alpha-net","pb-212-psv359"],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":["nct05655312","nct05636618","nct06710756"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Seattle, WA","country":"US","companyType":"radiopharma","website":"https://perspectivetherapeutics.com","ticker":"CATX","investors":[],"funding":[],"route":"/companies/perspective-therapeutics/"}
{"id":"petnet-solutions","kind":"company","name":"PETNET Solutions (Siemens Healthineers)","aka":[],"tldr":"PETNET Solutions is the largest network of PET radiopharmacies in the US, producing FDG and PSMA tracers daily.","summary":"PETNET Solutions, part of Siemens Healthineers and based in Knoxville, Tennessee, is the largest network of PET radiopharmacies in the United States, producing FDG and PSMA tracers every day. It operates about fifty cyclotron sites in the United States plus international operations and is the commercial distributor for several FDA-approved PET drugs. Nuclide links it to radiopharmacy and cyclotron networks and PET tracer manufacturing and distribution, and to the fludeoxyglucose F-18 drug record. Whether a network built for FDG can adapt to the many new PSMA, FAP and receptor tracers coming through is the open question. FDG has its own page.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.siemens-healthineers.com/molecular-imaging/petnet"}],"tags":["supporting"],"related":["f-18"],"indications":[],"sections":[],"technologies":["radiopharmacy-network","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Knoxville, TN","country":"US","companyType":"radiopharma","website":"https://www.siemens-healthineers.com/molecular-imaging/petnet","investors":[],"funding":[],"route":"/companies/petnet-solutions/"}
{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","aka":["Seagen","Seagen (Pfizer)","Seattle Genetics"],"tldr":"Bought Seagen for $43B to become an ADC leader; also makes Ibrance, Lorbrena, Braftovi, and the first PROTAC.","summary":"Pfizer, based in New York and listed as PFE, bought Seagen for 43 billion dollars to become an antibody-drug conjugate leader, and it also makes Ibrance, Lorbrena and Braftovi and developed the first PROTAC, vepdegestrant, with Arvinas. The ADC portfolio covers Padcev, Adcetris, Tivdak, Tukysa, disitamab vedotin outside China and sigvotatug vedotin; the small-molecule side includes palbociclib, atirmociclib, lorlatinib, encorafenib and talazoparib; and a PD-1 by VEGF bispecific was licensed from 3SBio in 2025 with 1.25 billion dollars upfront. Nuclide links it to the EV-302, CROWN, BREAKWATER, ECHELON-1 and INO-VATE papers, to ponsegromab and cachexia as a treatable disease, to LIV-1 as a target and to Pfizer Ventures. Whether Seagen's platform yields new ADCs rather than only sustaining the acquired ones is the open question. Each product has its own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.pfizer.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["dexrazoxane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"New York, NY","country":"US","companyType":"pharma","website":"https://www.pfizer.com","ticker":"PFE","investors":[],"funding":[],"route":"/companies/pfizer/"}
{"id":"point-biopharma","kind":"company","name":"POINT Biopharma","aka":[],"tldr":"POINT Biopharma developed radioactive medicines that home in on prostate cancer and neuroendocrine tumours, and built a large manufacturing campus in Indianapolis. Eli Lilly bought the company at the end of 2023.","summary":"POINT Biopharma Global Inc. (formerly Nasdaq: PNT) was an Indianapolis radiopharmaceutical company with late-stage radioligand therapies: PNT2002, a PSMA-targeted therapy for metastatic castration-resistant prostate cancer after progression on hormonal treatment, and PNT2003, a somatostatin receptor (SSTR)-targeted therapy for gastroenteropancreatic neuroendocrine tumours, both partnered with Lantheus outside certain Asian territories, plus earlier clinical and preclinical programmes. It operated a 180,000 square foot radiopharmaceutical manufacturing campus in Indianapolis and an R&D centre in Toronto. On 2 October 2023 Eli Lilly agreed to acquire POINT through a cash tender offer of USD 12.50 per share, and the merger was completed in late December 2023; the company website now redirects to lilly.com.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.lilly.com/"},{"label":"Form 8-K: merger agreement with Eli Lilly","url":"https://www.sec.gov/Archives/edgar/data/1811764/000110465923106146/tm2327397d1_8k.htm"},{"label":"Lilly press release (8-K exhibit 99.4)","url":"https://www.sec.gov/Archives/edgar/data/1811764/000110465923106146/tm2327397d1_ex99-4.htm"},{"label":"Form 8-K: completion of merger","url":"https://www.sec.gov/Archives/edgar/data/1811764/000119312523303512/d594310d8k.htm"}],"tags":[],"related":[],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma","sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["pointbiopharma.com redirects to lilly.com, recorded as the website. Deal value and pipeline details come from the Lilly press release filed as exhibit 99.4 to POINT's 8-K of 3 October 2023."],"hq":"Indianapolis, IN","country":"US","companyType":"radiopharma","website":"https://www.lilly.com/","stage":"acquired","investors":[],"funding":[{"round":"Acquisition","year":2023,"amountUsd":1400000000,"source":"https://www.sec.gov/Archives/edgar/data/1811764/000110465923106146/tm2327397d1_ex99-4.htm","note":"Cash tender offer at USD 12.50 per share, an aggregate of approximately USD 1.4 billion, under a merger agreement dated 2 October 2023; completion reported in an 8-K filed 27 December 2023"}],"acquiredBy":"eli-lilly","route":"/companies/point-biopharma/"}
{"id":"precirix","kind":"company","name":"Precirix","aka":[],"tldr":"Precirix, of Brussels, develops radiopharmaceuticals built on small single-domain antibody fragments that carry a radioactive isotope to HER2-positive cancers. Its lead, CAM-H2, is in a phase 1/2 trial in HER2-positive breast, gastric and gastro-oesophageal cancer, including patients with brain metastases, with an imaging dose given first to confirm HER2 in the lesions.","summary":"Precirix is a clinical-stage Brussels biotechnology company developing precision radiopharmaceuticals in oncology based on single-domain antibody (sdAb) targeting. Its lead candidate CAM-H2 is a HER2-directed radiopharmaceutical in a phase 1/2 trial, initially in Canada, evaluating safety, tolerability and efficacy in HER2-positive metastatic breast, gastric and gastro-oesophageal cancer, including patients with brain metastases. Patients first receive an imaging dose to confirm HER2 expression in lesions before therapeutic dosing. In June 2023 Precirix announced production of a first clinical trial batch of CAM-H2 at Evergreen Theragnostics in New Jersey to support expansion of the trial to the United States.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.evergreentgn.com/2023/06/08/cam-h2-production-at-evergreen-marks-the-expansion-of-precirix-clinical-trial-to-the-us/"}],"tags":[],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":["radioligand-therapy"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Financing (a EUR 80 million Series B reported by Fierce Biotech, whose page returned HTTP 403) is omitted as unsourced. Current operating status is uncertain given the offline website."],"hq":"Brussels","country":"BE","companyType":"radiopharma","website":"https://www.evergreentgn.com/2023/06/08/cam-h2-production-at-evergreen-marks-the-expansion-of-precirix-clinical-trial-to-the-us/","stage":"startup","investors":[],"funding":[],"route":"/companies/precirix/"}
{"id":"radiomedix","kind":"company","name":"RadioMedix","aka":[],"tldr":"RadioMedix is developing AlphaMedix (212Pb-DOTAMTATE) with Orano Med, the first targeted alpha therapy to receive FDA Breakthrough designation.","summary":"RadioMedix, based in Houston, is developing AlphaMedix, or 212Pb-DOTAMTATE, with Orano Med, the first targeted alpha therapy to receive FDA Breakthrough designation. AlphaMedix met all primary efficacy endpoints in phase 2, with a 60 percent objective response rate in PRRT-naive gastroenteropancreatic neuroendocrine tumour patients reported at ESMO 2025, was licensed to Sanofi with Orano Med in 2024, and has its next trial planned for late 2026; the company marked twenty years at SNMMI 2026. Nuclide links it to neuroendocrine tumours, to targeted alpha therapy and peptide receptor radionuclide therapy, to somatostatin receptor 2 as a target, and to Orano Med and Sanofi. Whether a lead-212 alpha emitter beats existing beta-emitter PRRT in a randomised trial is the open question. 212Pb-DOTAMTATE has its own page.","asOf":"2026-09-04","links":[{"label":"Sanofi licensing agreement","url":"https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-12-05-00-00-2944919"}],"tags":[],"related":["pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["sstr2"],"drugs":[],"companies":["orano-med"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Houston, TX","country":"US","companyType":"radiopharma","website":"https://www.radiomedix.com","investors":[],"funding":[],"route":"/companies/radiomedix/"}
{"id":"radionetics-oncology","kind":"company","name":"Radionetics Oncology","aka":[],"tldr":"Radionetics Oncology makes small-molecule drugs that carry a radioactive isotope to receptors on the surface of cancer cells that have rarely been targeted before. Eli Lilly paid 140 million dollars in 2024 for the right to buy the company for 1 billion dollars.","summary":"Radionetics Oncology, a San Diego company that emerged from Crinetics Pharmaceuticals in October 2021, discovers and develops small-molecule radiopharmaceuticals against G protein-coupled receptor (GPCR) targets not previously pursued by radiopharmaceuticals, identified through AI-driven multi-omics. Its first phase 1 radiopharmaceutical programme, against a novel target for adrenocortical carcinoma, was initiated in October 2023. In January 2024 the company raised a USD 52.5 million Series A led by Frazier Life Sciences, 5AM Ventures and DCVC Bio, appointing Paul Grayson as CEO. In July 2024 it entered a strategic agreement with Eli Lilly under which Radionetics received a USD 140 million upfront payment and Lilly obtained the exclusive right to acquire the company for USD 1 billion after an exercise period, during which Radionetics continues to build its GPCR-targeted pipeline.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://radionetics.com/"},{"label":"Series A press release","url":"https://radionetics.com/news/radionetics-oncology-raises-52-5m-series-a"},{"label":"Lilly strategic agreement release","url":"https://radionetics.com/news/radionetics-oncology-enters-into-strategic-agreement-with-lilly"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The USD 140 million Lilly upfront payment is a strategic agreement, not an equity round, so it is described in the summary rather than in funding."],"hq":"San Diego, CA","country":"US","companyType":"radiopharma","website":"https://radionetics.com/","founded":2021,"stage":"startup","investors":[],"funding":[{"round":"Series A","year":2024,"amountUsd":52500000,"source":"https://radionetics.com/news/radionetics-oncology-raises-52-5m-series-a","note":"Brought total raised to USD 82.5 million"}],"route":"/companies/radionetics-oncology/"}
{"id":"radiopharm-theranostics","kind":"company","name":"Radiopharm Theranostics","aka":["Radiopharm Theranostics, Ltd"],"tldr":"Radiopharm Theranostics is an Australia-based radiopharmaceutical company that leads 3 cancer trials in Nuclide, testing the radiopharmaceuticals 161Tb-RAD402, 177Lu-BetaBart and the PET tracer RAD101 in prostate cancer, colorectal cancer, non-small-cell lung cancer and ovarian cancer.","summary":"Radiopharm Theranostics is a clinical-stage company developing radiopharmaceuticals for the diagnosis and treatment of cancer, using nanobody, antibody, small-molecule and peptide platforms directed at targets other than PSMA, FAP and SSTR2. It has a joint venture with MD Anderson Cancer Center and is listed in Australia and on Nasdaq. On ClinicalTrials.gov it is the lead sponsor of 3 trials recorded in Nuclide: NCT07189871 (phase 1/2, 177Lu-BetaBart in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Me...), NCT07259213 (phase 1/2, A Study of Terbium 161 (161Tb)-RAD402 in Participants With CRPC) and NCT06777433 (phase 2, Phase 2b Imaging Study of RAD101 in Participants With Suspected Recurrent Brain Metastases). Sponsor and trial facts are from the ClinicalTrials.gov registry; company facts are from the official website.","asOf":"2026-09-17","links":[{"label":"Official website","url":"https://radiopharmtheranostics.com/"},{"label":"ClinicalTrials.gov: trials led by Radiopharm Theranostics","url":"https://clinicaltrials.gov/search?lead=Radiopharm%20Theranostics%2C%20Ltd"}],"tags":["ctgov-sponsor"],"related":["lu-177","tb-161"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07189871","nct07259213","nct06777433"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide orphan-trial linking round (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-17"},"hq":"Melbourne","country":"AU","companyType":"radiopharma","website":"https://radiopharmtheranostics.com/","ticker":"ASX:RAD, NASDAQ:RADX","founded":2021,"stage":"public","investors":[],"funding":[],"route":"/companies/radiopharm-theranostics/"}
{"id":"ratio-therapeutics","kind":"company","name":"Ratio Therapeutics","aka":[],"tldr":"Ratio Therapeutics, of Boston, designs small molecules that carry a radioactive isotope to fibroblast activation protein, a protein on the supporting tissue of sarcomas and other solid tumours, so radiation is delivered from inside the body. Its lead, an actinium-225 radioligand, is in the ATLAS phase 1/2 trial in advanced sarcomas.","summary":"Ratio Therapeutics is a clinical-stage Boston radiopharmaceutical company whose Trillium targeting scaffold combines pharmacokinetic modulation with chelation chemistry to create small-molecule radioligands that can be paired with imaging or therapeutic isotopes (theranostics). The lead programme [Ac-225]RTX-2358 is a fibroblast activation protein (FAP)-targeted actinium-225 therapeutic in the ATLAS phase 1/2 trial in advanced sarcomas; the pipeline also includes a next-generation GRPR programme and additional mono- and bispecific radioligands, with a fifth IND filing in preparation. In July 2026 Ratio closed a USD 70 million Series C with Duquesne Family Office, Bristol Myers Squibb, Catalio Capital, Eli Lilly and Wasatch Group, taking total capital raised above USD 240 million. It has manufacturing collaborations with PharmaLogic, an actinium-225 supply agreement with PanTera (June 2026) and, in September 2026, a research collaboration and licence agreement with RayzeBio.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://ratiotx.com/"},{"label":"Series C press release","url":"https://ratiotx.com/2026/07/31/ratio-therapeutics-closes-70-million-series-c-financing-to-advance-clinical-development-of-targeted-radiotherapeutics-pipeline-and-expand-manufacturing-infrastructure/"},{"label":"News","url":"https://ratiotx.com/news1/"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Earlier rounds (Series A and B) not fetched and omitted."],"hq":"Boston, MA","country":"US","companyType":"radiopharma","website":"https://ratiotx.com/","stage":"growth","investors":[],"funding":[{"round":"Series C","year":2026,"amountUsd":70000000,"source":"https://ratiotx.com/2026/07/31/ratio-therapeutics-closes-70-million-series-c-financing-to-advance-clinical-development-of-targeted-radiotherapeutics-pipeline-and-expand-manufacturing-infrastructure/","note":"Brings total capital raised to over USD 240 million"}],"route":"/companies/ratio-therapeutics/"}
{"id":"rayzebio","kind":"company","name":"RayzeBio (BMS)","aka":[],"tldr":"RayzeBio is the actinium-225 radiopharma company that BMS bought for $4.1B; its RYZ101 is in phase 3.","summary":"RayzeBio, based in San Diego, is the actinium-225 radiopharmaceutical company that Bristol Myers Squibb bought for 4.1 billion dollars, and its RYZ101 is in phase 3. RYZ101 is actinium-225 DOTATATE for somatostatin-receptor-positive neuroendocrine tumours, RYZ801 is an actinium-225 PSMA agent, and the company built in-house actinium-225 manufacturing. Nuclide links it to neuroendocrine tumours, to peptide receptor radionuclide therapy and targeted alpha therapy, to the actinium-225 DOTATATE drug record, and to the radiopharmaceutical roadmap from iodine through lutetium to actinium. Whether an alpha emitter can improve on lutetium-based radioligand therapy is the question RYZ101's phase 3 will answer. Actinium-225 DOTATATE has its own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.rayzebio.com"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["ryz101"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06590857","nct06726161"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"San Diego, CA","country":"US","companyType":"radiopharma","website":"https://www.rayzebio.com","investors":[],"funding":[],"route":"/companies/rayzebio/"}
{"id":"shine-technologies","kind":"company","name":"SHINE Technologies","aka":[],"tldr":"SHINE Technologies is a fusion-based isotope company that produces non-carrier-added Lu-177 (Ilumira) and is building the Chrysalis Mo-99 plant.","summary":"SHINE Technologies, based in Janesville, Wisconsin, is a fusion-based isotope company that produces non-carrier-added lutetium-177, sold as Ilumira, and is building the Chrysalis molybdenum-99 plant. It has supplied lutetium-177 to radiopharmaceutical developers since 2022, its large-scale Mo-99 facility is under construction, and it holds long-term fusion energy ambitions. Nuclide links it to the therapeutic isotope supply chain for Mo-99, Lu-177 and Ac-225. Whether a second Western source of lutetium-177 makes supply resilient enough for radioligand therapy to scale is the open question. The isotope supply chain page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.shinefusion.com"}],"tags":["supporting"],"related":["mo-99","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Janesville, WI","country":"US","companyType":"radiopharma","website":"https://www.shinefusion.com","investors":[],"funding":[],"route":"/companies/shine-technologies/"}
{"id":"siemens-healthineers","kind":"company","name":"Siemens Healthineers","aka":[],"tldr":"Siemens Healthineers makes the Biograph Vision Quadra total-body PET and photon-counting CT, and owns Varian.","summary":"Siemens Healthineers, based in Erlangen, makes the Biograph Vision Quadra total-body PET scanner and the NAEOTOM Alpha photon-counting CT, alongside MAGNETOM MRI, and it owns the radiotherapy company Varian. Nuclide links it to PET/CT, CT and MRI as technologies, to nuclear medicine and total-body PET hardware, total-body PET for screening and ultra-low-dose imaging, AI auto-contouring and medical cyclotrons, and to ideas on total-body PET for personalised radioligand dosing and on validating and reimbursing AI contouring to expand radiotherapy capacity. Owning both imaging and radiotherapy gives it a position across the treatment pathway that few rivals share. Whether total-body PET moves from research instrument to routine clinical tool is the open question. Varian has its own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.siemens-healthineers.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-ct","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Erlangen","country":"DE","companyType":"imaging","website":"https://www.siemens-healthineers.com","investors":[],"funding":[],"route":"/companies/siemens-healthineers/"}
{"id":"sinotau-pharmaceutical","kind":"company","name":"Sinotau Pharmaceutical","aka":["Sinotau Pharmaceutical Group"],"tldr":"Sinotau Pharmaceutical is a China-based radiopharmaceutical company running 2 late-stage cancer trials of Octreotide LAR in neuroendocrine tumours.","summary":"Sinotau Pharmaceutical, based in Beijing, China, is a radiopharmaceutical company. Sinotau specialises in the research and development, production, clinical application and academic promotion of radiopharmaceutical drugs, with therapeutic focus areas in oncology, neurology and cardiology. On ClinicalTrials.gov it is the lead sponsor of 2 recruiting or active phase 2 and phase 3 interventional cancer trials (2 in phase 3), testing Octreotide LAR in neuroendocrine tumours. The largest, NCT05459844 (A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs), plans to enrol 196 participants (actual). Sponsor and trial facts are from the ClinicalTrials.gov registry; company facts are from the official website.","asOf":"2026-09-11","links":[{"label":"Official website","url":"https://www.sinotau.com/"},{"label":"ClinicalTrials.gov: trials led by Sinotau Pharmaceutical","url":"https://clinicaltrials.gov/search?lead=Sinotau%20Pharmaceutical%20Group"}],"tags":["ctgov-sponsor"],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05459844","nct06398444"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Beijing","country":"CN","companyType":"radiopharma","website":"https://www.sinotau.com/","founded":2014,"stage":"private-large","investors":[],"funding":[],"route":"/companies/sinotau-pharmaceutical/"}
{"id":"sirtex","kind":"company","name":"Sirtex Medical","aka":[],"tldr":"Sirtex makes SIR-Spheres, yttrium-90 resin microspheres used for radioembolisation of liver tumours.","summary":"Sirtex Medical, based in Woburn, Massachusetts, and owned by China Grand Pharmaceutical, makes SIR-Spheres, yttrium-90 resin microspheres used for radioembolisation of liver tumours. SIR-Spheres are indicated in the United States for unresectable colorectal cancer metastatic to the liver and carry a CE mark for hepatocellular carcinoma, with the DOORwaY90 trial supporting a US indication in liver cancer, and they compete with Boston Scientific's TheraSphere glass microspheres. Nuclide links it to hepatocellular carcinoma and colorectal cancer and to the radioembolisation technology record. Whether radioembolisation earns a place alongside systemic immunotherapy combinations in liver cancer, rather than being displaced by them, is the open question. The technology page covers the evidence.","asOf":"2026-09-07","links":[{"label":"Official website","url":"https://www.sirtex.com"}],"tags":[],"related":["y-90"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Woburn, MA","country":"US","companyType":"devices","website":"https://www.sirtex.com","investors":[],"funding":[],"route":"/companies/sirtex/"}
{"id":"sofie-biosciences","kind":"company","name":"SOFIE Biosciences","aka":[],"tldr":"SOFIE Biosciences is a US radiopharmacy network running two phase 3 trials of the FAP PET tracer [18F]FAPI-74 in pancreatic and gastro-oesophageal cancer.","summary":"SOFIE Biosciences, based in Dulles, Virginia, is a US radiopharmacy network running two phase 3 trials of the FAP PET tracer 18F-FAPI-74 in pancreatic and gastro-oesophageal cancer. First patients were dosed in the FAPI-GO gastro-oesophageal trial in December 2025 and the pancreatic trial in February 2026, seven radiopharmacies have been cleared to manufacture 18F-FAPI-74 with twelve-hour shelf-life distribution planned in 2026, and the FAPI chemistry originated at Heidelberg. Nuclide links it to pancreatic, gastric and oesophageal cancer, to FAPI PET and PET, to FAP as a target, to Heidelberg University Hospital and the DKFZ, and to PET tracer manufacturing and radiopharmacy networks. Whether FAP imaging changes staging and treatment in cancers where FDG PET falls short is the question the phase 3 trials will answer. The FAPI PET technology page carries the evidence.","asOf":"2026-09-04","links":[{"label":"Phase 3 first patient","url":"https://sofie.com/2026/02/11/sofie-biosciences-announces-first-patient-dosed-in-18ffapi-74-phase-3-study-for-pancreatic-cancer/"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["fapi-pet","pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":["nct07217704"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Dulles, VA","country":"US","companyType":"radiopharma","website":"https://sofie.com","investors":[],"funding":[],"route":"/companies/sofie-biosciences/"}
{"id":"spectrum-pharmaceuticals","kind":"company","name":"Spectrum Pharmaceuticals","aka":["Spectrum Pharmaceuticals, Inc","Spectrum Pharmaceuticals, Inc."],"tldr":"Spectrum Pharmaceuticals was a US cancer company that sold its haematology portfolio to Acrotech in 2019, won approval for the long-acting G-CSF eflapegrastim (Rolvedon) in 2022, and was acquired by Assertio in 2023.","summary":"Spectrum Pharmaceuticals, latterly based in Boston after years in Henderson, Nevada, marketed a haematology portfolio (Zevalin, Folotyn, Beleodaq, Marqibo and Evomela) that it sold to Acrotech Biopharma in 2019 to concentrate on two development programmes: poziotinib, an EGFR and HER2 exon 20 inhibitor that received a complete response letter in 2022, and eflapegrastim (Rolvedon), a long-acting G-CSF for chemotherapy-induced neutropenia approved by the FDA in September 2022. Assertio Holdings acquired the company in 2023. It appears on Nuclide as one of the most frequent industry sponsors of phase 3 cancer trials on the registry.","asOf":"2026-09-11","wikipedia":"https://en.wikipedia.org/wiki/Spectrum_Pharmaceuticals","links":[{"label":"ClinicalTrials.gov: trials led by Spectrum Pharmaceuticals","url":"https://clinicaltrials.gov/search?lead=Spectrum%20Pharmaceuticals"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Spectrum_Pharmaceuticals"}],"tags":["ctgov-sponsor"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["acrotech-biopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"Nuclide ingestion (ClinicalTrials.gov v2 + sponsor websites)","editedOn":"2026-09-11"},"hq":"Boston, MA","country":"US","companyType":"biotech","website":"https://www.spectrumpharm.com","stage":"acquired","investors":[],"funding":[],"route":"/companies/spectrum-pharmaceuticals/"}
{"id":"telix","kind":"company","name":"Telix Pharmaceuticals","aka":[],"tldr":"Telix is the Australian theranostics company behind Illuccix and Gozellix PSMA imaging and a broad therapeutic pipeline.","summary":"Telix Pharmaceuticals, based in Melbourne and listed as TLX.AX, is the Australian theranostics company behind the Illuccix and Gozellix kits for gallium-68 PSMA-11 imaging and a broad therapeutic pipeline. TLX250-CDx, or zirconium-89 girentuximab for carbonic anhydrase IX PET in kidney cancer, received an FDA complete response letter in 2025, TLX591, or lutetium-177 rosopatamab, a PSMA antibody in the ProstACT phase 3, and TLX101 for glioma follow. Nuclide links it to prostate cancer and renal cell carcinoma, to PSMA as a target, to CAIX PET and PET tracer manufacturing, and to the idea of CAIX theranostics pairing girentuximab imaging with lutetium or actinium therapy. Whether an antibody-based PSMA therapy can compete with small-molecule ligands is the open question. Illuccix has its own page.\n\nIts lung-cancer position is entirely pre-clinical, which is worth stating plainly because the company is often named in the same breath as lung radiopharmaceuticals. No asset on the published pipeline carries a lung indication, and ClinicalTrials.gov returns no recruiting Telix lung-cancer study. What exists is two commitments. In January 2025 Telix bought a pipeline of early-stage therapeutic candidates and a biologics platform from ImaginAb for US$45 million plus up to US$185 million in milestones, including a discovery-stage programme against DLL3, the surface protein of small-cell lung cancer, with no TLX code or isotope assigned. In April 2026 it signed a collaboration with Regeneron covering four initial programmes built on Regeneron antibodies, for US$40 million upfront, an equal share of costs and profits and up to US$2.1 billion in milestones; Telix’s own second-quarter 2026 results describe that collaboration as initially focused on lung cancer.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://telixpharma.com"},{"label":"Telix and Regeneron announce strategic radiopharma collaboration (13 April 2026)","url":"https://telixpharma.com/news-views/telix-and-regeneron-announce-strategic-radiopharma-collaboration/"},{"label":"Telix Q2 2026 results: the Regeneron collaboration is \"initially focused on lung cancer\" (21 July 2026)","url":"https://telixpharma.com/news-views/telix-q2-2026-revenue-us247m-strong-momentum-and-pipeline-progress/"},{"label":"Telix asset purchase from ImaginAb, including a discovery-stage DLL3 programme for small-cell lung cancer (13 January 2025)","url":"https://www.sec.gov/Archives/edgar/data/2007191/000200719125000003/frelease.htm"},{"label":"Telix pipeline (no lung indication listed)","url":"https://telixpharma.com/our-pipeline/"}],"tags":[],"related":["sclc","nsclc","ga-68","zr-89","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":["psma","dll3"],"drugs":["girentuximab-zr89"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06520345","nct07052214"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Melbourne","country":"AU","companyType":"radiopharma","website":"https://telixpharma.com","ticker":"TLX.AX","investors":[],"funding":[],"route":"/companies/telix/"}
{"id":"terrapower-isotopes","kind":"company","name":"TerraPower Isotopes","aka":[],"tldr":"Bill Gates-backed producer of actinium-225 from thorium-229, building a Philadelphia facility to raise supply 20-fold.","summary":"TerraPower Isotopes, based in Bellevue, Washington, is the Bill Gates-backed producer of actinium-225 from thorium-229, building a Philadelphia facility intended to raise supply twenty-fold. It obtains actinium-225 from the decay of thorium-229 recovered from a legacy uranium-233 stockpile and holds supply agreements with Bayer, Bristol Myers Squibb and others. Nuclide links it to targeted alpha therapy, alpha-emitter nanogenerators and the therapeutic isotope supply chain, to the radiopharmaceutical roadmap from iodine to actinium, and to the idea of recovering legacy radium-226 sources worldwide as feedstock. Manufacturing cost and time for radioactive medicines is the bottleneck it exists to relieve. Whether supply can grow fast enough for the alpha therapies now in phase 3 is the open question.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.terrapower.com/isotopes"}],"tags":["isotope-supply"],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Bellevue, WA","country":"US","companyType":"radiopharma","website":"https://www.terrapower.com/isotopes","investors":[],"funding":[],"route":"/companies/terrapower-isotopes/"}
{"id":"trasis","kind":"company","name":"Trasis","aka":[],"tldr":"Belgian maker of radiopharmaceutical synthesis modules (AllinOne, miniAiO) and dose dispensers used in PET and therapy radiopharmacies.","summary":"Trasis, based in Ans, Belgium, makes radiopharmaceutical synthesis modules, including AllinOne and miniAiO, and dose dispensers used in PET and therapy radiopharmacies. Its cassette-based automated radiochemistry and cyclotron target solutions are widely used for gallium-68, fluorine-18 and lutetium-177 labelling. Nuclide links it to medical cyclotrons, hot cells and synthesis modules. Whether synthesis automation can keep pace with the many new tracers and therapeutic ligands entering the clinic is the open question for its market. The cyclotron and synthesis technology page carries the wider picture.","asOf":"2026-09-08","links":[{"label":"Official website","url":"https://www.trasis.com"}],"tags":["supporting"],"related":["f-18","ga-68","lu-177"],"indications":[],"sections":[],"technologies":["medical-cyclotrons-synthesis-modules"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Ans","country":"BE","companyType":"radiopharma","website":"https://www.trasis.com","investors":[],"funding":[],"route":"/companies/trasis/"}
{"id":"united-imaging","kind":"company","name":"United Imaging","aka":[],"tldr":"Chinese imaging company that built uEXPLORER, the first total-body PET scanner.","summary":"United Imaging, based in Shanghai and listed as 688271.SS, is the Chinese imaging company that built uEXPLORER, the first total-body PET scanner. The uEXPLORER has a 194 centimetre axial field of view and about forty times the sensitivity of a conventional scanner, the uMI Panorama is its other PET platform, and the company has a growing presence in the United States. Nuclide links it to PET/CT, to nuclear medicine and total-body PET hardware and total-body PET for screening and ultra-low-dose imaging, to the molecular imaging roadmap, and to ideas on total-body PET for personalised radioligand dosing and on open-hardware machines for difficult environments. Whether ultra-sensitive scanners lead to lower-dose or cheaper imaging in practice is the open question. The total-body PET technology page carries the detail.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.united-imaging.com"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Shanghai","country":"CN","companyType":"imaging","website":"https://www.united-imaging.com","ticker":"688271.SS","investors":[],"funding":[],"route":"/companies/united-imaging/"}
{"id":"y-mabs","kind":"company","name":"Y-mAbs Therapeutics","aka":[],"tldr":"MSK spin-out that commercialises naxitamab, the humanised anti-GD2 antibody for relapsed neuroblastoma, and develops pretargeted radioimmunotherapy.","summary":"Y-mAbs Therapeutics, based in New York and listed as YMAB, is a Memorial Sloan Kettering spin-out that commercialises naxitamab, the humanised anti-GD2 antibody for relapsed neuroblastoma, and develops pretargeted radioimmunotherapy. Naxitamab, sold as Danyelza, received accelerated approval in November 2020; omburtamab, a B7-H3 antibody carrying iodine-131, was rejected by the FDA in 2022; and the SADA pretargeted radioimmunotherapy platform, with a GD2-SADA and lutetium-177 pairing, is in phase 1. Nuclide links it to paediatric neuroblastoma, to GD2 as a target and to the bottleneck of rare and paediatric cancers without markets. Whether pretargeting can deliver radiation to paediatric tumours with less marrow toxicity than direct radioimmunotherapy is the open question. Naxitamab has its own page.","asOf":"2026-09-07","links":[{"label":"Official website","url":"https://www.ymabs.com"}],"tags":[],"related":["lu-177","i-131"],"indications":["neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"New York, NY","country":"US","companyType":"biotech","website":"https://www.ymabs.com","ticker":"YMAB","investors":[],"funding":[],"route":"/companies/y-mabs/"}
{"id":"aiims-delhi","kind":"institution","name":"All India Institute of Medical Sciences, New Delhi","aka":["AIIMS","Dr B.R. Ambedkar Institute Rotary Cancer Hospital","National Cancer Institute Jhajjar"],"tldr":"AIIMS New Delhi is India's flagship public medical institute; its Rotary Cancer Hospital and the National Cancer Institute campus at Jhajjar anchor government cancer research, and its investigators lead Indian studies in paediatric oncology, gallbladder cancer, PSMA radioligand therapy and low-cost CAR-T.","summary":"AIIMS New Delhi was created by an Act of Parliament in 1956 as India's flagship medical institute and hospital. Cancer care is concentrated in the Dr B.R. Ambedkar Institute Rotary Cancer Hospital, opened in 1983, and in the National Cancer Institute at Jhajjar, Haryana, a large AIIMS-run cancer campus commissioned from 2019 with proton therapy planned and a national biobank and screening research mandate. AIIMS investigators lead Indian studies in paediatric oncology, gallbladder cancer (unusually common in northern India), oral and cervical cancer screening, radiation oncology and nuclear medicine (PSMA and FAPI PET, radioligand therapy), and haematology including low-cost CAR-T development with IIT Bombay partners. It sets national training standards and publishes the largest volume of oncology research of any Indian public institution.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/All_India_Institute_of_Medical_Sciences,_Delhi","links":[{"label":"AIIMS New Delhi","url":"https://www.aiims.edu"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet","fapi-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"New Delhi","country":"IN","lat":28.567,"lng":77.21,"institutionType":"hospital","website":"https://www.aiims.edu","programs":["Rotary Cancer Hospital","National Cancer Institute Jhajjar","Nuclear medicine and theranostics","Paediatric oncology","Gallbladder cancer"],"route":"/institutions/aiims-delhi/"}
{"id":"anzup","kind":"institution","name":"ANZUP Cancer Trials Group","aka":["Australian and New Zealand Urogenital and Prostate Cancer Trials Group","ANZUP"],"tldr":"The Australian genitourinary trials group behind TheraP and proPSMA, the trials that put PSMA imaging and lutetium-PSMA therapy on the map.","summary":"Formed in 2008 to unite Australia and New Zealand's prostate, kidney, bladder, testicular and penile cancer researchers. ANZUP 1603 TheraP was the first randomised trial of lutetium-177 PSMA-617, showing higher PSA response than cabazitaxel and paving the way for VISION and the Pluvicto approval, and proPSMA (ANZUP 1702) showed PSMA PET-CT outperforms conventional imaging for staging high-risk prostate cancer. ENZAMET and ENZARAD tested enzalutamide with docetaxel and with radiotherapy. Trials are run through the NHMRC Clinical Trials Centre at the University of Sydney, and consumer advisory panels are built into every study.","asOf":"2026-09-09","links":[{"label":"ANZUP","url":"https://anzup.org.au"},{"label":"Trials","url":"https://anzup.org.au/trials/"}],"tags":[],"related":["lu-177"],"indications":["prostate","rcc"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":["peter-mac"],"pathways":[],"terms":["theranostics"],"trials":["therap","propsma"],"people":["hofman-michael","sandhu-shahneen"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Sydney","country":"AU","lat":-33.868,"lng":151.209,"institutionType":"consortium","website":"https://anzup.org.au","programs":["TheraP (Lu-PSMA vs cabazitaxel)","proPSMA (PSMA PET staging)","ENZAMET / ENZARAD","Bladder and kidney cancer trials","Consumer involvement"],"route":"/institutions/anzup/"}
{"id":"ccc-wuerzburg","kind":"institution","name":"Comprehensive Cancer Center Mainfranken, University Hospital Würzburg","aka":["CCC Mainfranken","Universitätsklinikum Würzburg","NCT WERA"],"tldr":"The university where Röntgen discovered X-rays, now a world centre for CAR-T and bispecific antibodies in multiple myeloma under Hermann Einsele.","summary":"Wilhelm Conrad Röntgen discovered X-rays at Würzburg in 1895, the founding moment of radiation medicine. Today the CCC Mainfranken is a German Cancer Aid Oncology Center of Excellence and, with Erlangen, Regensburg and Augsburg, one of the National Center for Tumor Diseases sites (NCT WERA) since 2023. Hermann Einsele's Department of Internal Medicine II has been a leading European site for BCMA-directed CAR-T and bispecific antibodies in myeloma, including the CARTITUDE and MajesTEC programmes, and was among the first in Europe to treat patients with these agents. The centre also has strong programmes in stem cell transplantation, neuro-oncology, nuclear medicine and theranostics, and translational immunology.","asOf":"2026-09-09","links":[{"label":"CCC Mainfranken","url":"https://www.ccc.ukw.de"},{"label":"Universitätsklinikum Würzburg","url":"https://www.ukw.de"},{"label":"NCT WERA","url":"https://www.nct-wera.de"}],"tags":[],"related":[],"indications":["dlbcl"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Würzburg","country":"DE","lat":49.802,"lng":9.957,"institutionType":"cancer-center","website":"https://www.ccc.ukw.de","university":"Julius-Maximilians-Universität Würzburg","programs":["Multiple myeloma CAR-T and bispecifics","Stem cell transplantation","Theranostics","NCT WERA"],"route":"/institutions/ccc-wuerzburg/"}
{"id":"centre-eugene-marquis","kind":"institution","name":"Centre Eugène Marquis","aka":[],"tldr":"The Unicancer cancer centre for Brittany in Rennes, accredited by OECI as a Comprehensive Cancer Centre.","summary":"Centre Eugène Marquis is the Centre de Lutte Contre le Cancer for Rennes and Brittany, one of the 18 Unicancer centres in France. It provides medical oncology, radiotherapy, nuclear medicine and supportive care on the Pontchaillou campus shared with the CHU de Rennes, and its research groups work with Inserm and the University of Rennes on radiotherapy physics, medical imaging and cancer genomics. The centre is accredited by the Organisation of European Cancer Institutes as a Comprehensive Cancer Centre and coordinates regional cancer research through the Breton cancer network.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.centre-eugene-marquis.fr"}],"tags":["oeci-accredited","oeci-comprehensive-cancer-centre","unicancer"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Rennes","country":"FR","lat":48.117,"lng":-1.68,"institutionType":"cancer-center","website":"https://www.centre-eugene-marquis.fr","programs":["Radiotherapy physics","Nuclear medicine","Cancer genomics"],"route":"/institutions/centre-eugene-marquis/"}
{"id":"charite","kind":"institution","name":"Charité Universitätsmedizin Berlin","aka":["Charité Comprehensive Cancer Center","Charité Comprehensive Cancer Center (CCCC)"],"tldr":"Charité is Europe's largest university hospital, with a Comprehensive Cancer Center and the Berlin Institute of Health.","summary":"Charité, Universitätsmedizin Berlin, is Europe's largest university hospital and hosts the Charité Comprehensive Cancer Center and the Berlin Institute of Health; it ranks twelfth in the Newsweek/Statista oncology list. Its cancer strengths lie in haematology, cell therapy and translational research carried out with the Max Delbrück Center for Molecular Medicine, with Ulrich Keilholz, Christof von Kalle, Lars Bullinger and the paediatric oncologist Angelika Eggert among its leaders. Nuclide links it to the Atlas pathology foundation model developed with Aignostics and Mayo Clinic, to Deutsche Krebshilfe and SIOP Europe, and to the idea of hospital-exemption cell therapies made at scale with a shared registry. Whether academic cell therapy manufacturing can match industry on quality and cost is the open question. Its cell therapy programme is the place to start.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.charite.de"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Berlin","country":"DE","lat":52.527,"lng":13.377,"institutionType":"university","website":"https://www.charite.de","newsweekOncology2026":12,"programs":["Cell therapy","Haematology","Precision oncology"],"route":"/institutions/charite/"}
{"id":"curanosticum","kind":"institution","name":"Curanosticum Wiesbaden-Frankfurt","aka":[],"tldr":"Curanosticum is a nuclear medicine practice in Wiesbaden and Frankfurt led by Richard Baum, one of the pioneers of peptide receptor radionuclide therapy, offering FAPI PET and investigational radioligand therapies.","summary":"Curanosticum Wiesbaden-Frankfurt describes itself as modern nuclear medicine in the Rhine-Main region: precise diagnostics and individual therapy from an experienced team. Led by Richard Baum, it offers FAPI PET imaging and investigational radioligand therapies alongside established theranostics, and is patient-bookable through an oncology referral.","asOf":"2026-09-09","links":[{"label":"Official website","url":"https://www.curanosticum.de/"},{"label":"Listed on Future of Cancer Care Today (Sijbrandij Foundation)","url":"https://sijbrandijfoundation.org/fcct"}],"tags":["fcct-directory"],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy","fapi-pet","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["richard-baum"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Wiesbaden","country":"DE","lat":50.08,"lng":8.24,"institutionType":"hospital","website":"https://www.curanosticum.de/","programs":[],"route":"/institutions/curanosticum/"}
{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","aka":[],"tldr":"Where chemotherapy began (Farber, 1948) and where much of modern breast, lung, and myeloma oncology was defined.","summary":"Dana-Farber Brigham Cancer Center in Boston is where chemotherapy began, with Farber's aminopterin remissions in 1948, and through Dana-Farber/Harvard Cancer Center it is the largest NCI-designated centre by grant funding and fifteenth in the Newsweek/Statista oncology list. Its firsts include the discovery of EGFR mutations in lung cancer by Jänne and Johnson, KEYNOTE-522 leadership by Tolaney with Schmid in triple-negative breast cancer, Anderson's myeloma drug development and the Profile genomic testing programme. Nuclide links it to BWEL and RASolute 302, to pathology foundation models from the Mahmood and Yu labs, to the Cancer Dependency Map and clonal haematopoiesis papers, and to people including Paul G. Richardson, Benjamin L. Ebert and Ann H. Partridge. Data silos are the bottleneck Nuclide records against it. Its breast, lung, myeloma and paediatric programmes are listed below.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.dana-farber.org"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Boston","country":"US","lat":42.338,"lng":-71.108,"institutionType":"cancer-center","website":"https://www.dana-farber.org","nci":"comprehensive","newsweekOncology2026":15,"university":"Harvard University","programs":["Breast oncology (KEYNOTE-522, ADCs)","Lung cancer genomics","Myeloma","Paediatric oncology"],"route":"/institutions/dana-farber/"}
{"id":"eanm","kind":"institution","name":"European Association of Nuclear Medicine","aka":["EANM"],"tldr":"Europe's nuclear medicine society, whose congress and guidelines shaped the clinical adoption of PSMA PET and lutetium radioligand therapy that began in European centres.","summary":"Founded in 1985 and based in Vienna, EANM represents nuclear medicine across Europe and publishes the European Journal of Nuclear Medicine and Molecular Imaging. Its annual congress is the largest nuclear medicine meeting in Europe and was the early forum for PSMA-PET and Lu-177 PSMA work from Heidelberg, Munich, Bad Berka and other centres before the VISION trial. EANM issues procedure guidelines with SNMMI on PSMA PET, PRRT for neuroendocrine tumours, dosimetry and FDG PET response criteria, runs the EARL accreditation programme that harmonises PET scanners across trial sites, and operates the European School of Multimodality Imaging and Therapy. It advocates on isotope supply and reimbursement for theranostics in Europe.","asOf":"2026-09-09","links":[{"label":"EANM","url":"https://www.eanm.org"}],"tags":[],"related":["lu-177"],"indications":[],"sections":[],"technologies":["psma-pet","fapi-pet","pet-ct","radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":["snmmi","heidelberg-nct","lmu-munich"],"pathways":[],"terms":["theranostics","dosimetry"],"trials":[],"people":["uwe-haberkorn","frederik-giesel","clemens-kratochwil","paola-anna-erba"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Vienna","country":"AT","lat":48.208,"lng":16.373,"institutionType":"consortium","website":"https://www.eanm.org","programs":["EANM Congress","EARL PET accreditation","Procedure guidelines (with SNMMI)","European Journal of Nuclear Medicine and Molecular Imaging","ESMIT education"],"route":"/institutions/eanm/"}
{"id":"ema","kind":"institution","name":"European Medicines Agency","aka":["EMA","CHMP"],"tldr":"The EU agency whose Committee for Medicinal Products for Human Use recommends the marketing authorisations for cancer drugs across all member states.","summary":"Founded in 1995 in London and relocated to Amsterdam in 2019, the EMA coordinates the scientific evaluation of medicines for the European Union through the centralised procedure, which is mandatory for cancer drugs and advanced therapies. The Committee for Medicinal Products for Human Use (CHMP) issues opinions that the European Commission converts into EU-wide authorisations, while the Committee for Advanced Therapies handles CAR-T and gene therapies and PRIME gives early support to promising medicines. The agency publishes European Public Assessment Reports and clinical data, runs conditional marketing authorisation for unmet need, and since 2025 works alongside the EU Health Technology Assessment Regulation's joint clinical assessments, which begin with oncology medicines. Trial registration runs through CTIS.","asOf":"2026-09-09","links":[{"label":"EMA","url":"https://www.ema.europa.eu"},{"label":"CHMP","url":"https://www.ema.europa.eu/en/committees/committee-medicinal-products-human-use-chmp"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mhra"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Amsterdam","country":"NL","lat":52.339,"lng":4.873,"institutionType":"government","website":"https://www.ema.europa.eu","programs":["Centralised procedure and CHMP opinions","Committee for Advanced Therapies","PRIME and conditional marketing authorisation","Clinical data publication and CTIS"],"route":"/institutions/ema/"}
{"id":"erasmus-mc","kind":"institution","name":"Erasmus MC Cancer Institute","aka":["Erasmus MC","Daniel den Hoed","Erasmus University Medical Center"],"tldr":"Rotterdam's OECI-accredited comprehensive cancer centre, where peptide receptor radionuclide therapy with lutetium-177 was pioneered and Europe's largest screening trials were led.","summary":"Erasmus MC Cancer Institute unites the former Daniel den Hoed cancer clinic with the oncology departments of Erasmus University Medical Center and holds OECI comprehensive cancer centre accreditation. Its nuclear medicine group under Eric Krenning and Dik Kwekkeboom developed somatostatin-receptor imaging and then 177Lu-DOTATATE peptide receptor radionuclide therapy for neuroendocrine tumours, the treatment later validated in NETTER-1 and approved as Lutathera. Erasmus MC epidemiologists coordinated the European Randomized Study of Screening for Prostate Cancer and the NELSON lung screening trial, which showed a mortality reduction from low-dose CT screening. The institute co-founded the Holland Proton Therapy Centre in Delft with LUMC and TU Delft, and is a leading sarcoma, breast and neuro-oncology trial site under Stefan Sleijfer.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.erasmusmc.nl/en/cancer-institute"},{"label":"HollandPTC","url":"https://www.hollandptc.nl"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine","prostate","glioblastoma"],"sections":[],"technologies":["radioligand-therapy","spect","pet-ct","ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Rotterdam","country":"NL","lat":51.91,"lng":4.468,"institutionType":"cancer-center","website":"https://www.erasmusmc.nl/en/cancer-institute","university":"Erasmus University Rotterdam","programs":["Peptide receptor radionuclide therapy","Cancer screening trials (ERSPC, NELSON)","Holland Proton Therapy Centre","Sarcoma","Neuro-oncology"],"route":"/institutions/erasmus-mc/"}
{"id":"essen-wtz","kind":"institution","name":"West German Cancer Center (WTZ), University Hospital Essen","aka":["Westdeutsches Tumorzentrum","Universitätsklinikum Essen","NCT West"],"tldr":"One of Germany's oldest and largest cancer centres, home to the West German Proton Therapy Centre and a leading melanoma and theranostics programme.","summary":"Founded in 1967, the Westdeutsches Tumorzentrum at University Hospital Essen was among the first German Cancer Aid Oncology Centers of Excellence and became a National Center for Tumor Diseases site (NCT West, with Cologne) in 2023. It operates the West German Proton Therapy Centre Essen (WPE), Europe's largest university-based proton facility, treating many paediatric patients. The dermato-oncology group under Dirk Schadendorf has led melanoma immunotherapy and adjuvant trials, and the nuclear medicine department under Ken Herrmann is a high-volume theranostics centre for PSMA and somatostatin-receptor radioligands. Other strengths include sarcoma, uveal melanoma, stem cell transplantation and neuro-oncology.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.wtz-essen.de"},{"label":"WPE proton centre","url":"https://www.wpe-uk.de"},{"label":"NCT West","url":"https://www.nct-west.de"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":["iba"],"institutions":[],"pathways":[],"terms":[],"trials":["vision"],"people":["ken-herrmann"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Essen","country":"DE","lat":51.437,"lng":6.992,"institutionType":"cancer-center","website":"https://www.wtz-essen.de","university":"Universität Duisburg-Essen","programs":["West German Proton Therapy Centre","Melanoma and dermato-oncology","Theranostics and nuclear medicine","Stem cell transplantation","NCT West"],"route":"/institutions/essen-wtz/"}
{"id":"excel-diagnostics-nuclear-oncology","kind":"institution","name":"Excel Diagnostics and Nuclear Oncology Center","aka":[],"tldr":"Excel Diagnostics is a Houston nuclear medicine centre offering molecular imaging and radioligand therapies, bookable through an oncology referral.","summary":"Excel Diagnostics and Nuclear Oncology Center in Houston provides molecular imaging and theranostic treatments, the pairing of a targeted scan with a matched radioactive drug, for patients referred by their oncologists.","asOf":"2026-09-09","links":[{"label":"Official website","url":"https://exceldiagnostics.com/"},{"label":"Listed on Future of Cancer Care Today (Sijbrandij Foundation)","url":"https://sijbrandijfoundation.org/fcct"}],"tags":["fcct-directory"],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["ebrahim-delpassand"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Houston","country":"US","lat":29.74,"lng":-95.56,"institutionType":"hospital","website":"https://exceldiagnostics.com/","programs":[],"route":"/institutions/excel-diagnostics-nuclear-oncology/"}
{"id":"fuscc","kind":"institution","name":"Fudan University Shanghai Cancer Center","aka":[],"tldr":"Fudan University Shanghai Cancer Center is China's leading breast cancer centre and the site of first-in-human TROP2 PET imaging.","summary":"Fudan University Shanghai Cancer Center is China's leading breast cancer centre, ranked fifty-fifth in the Newsweek/Statista oncology list, and the site of the first-in-human TROP2 PET imaging study. Shao Zhimin's molecular subtyping of triple-negative breast cancer and the FUTURE umbrella trial built on it, the gallium-68 TROP2 nanobody PET tracer from Shaoli Song, and the highest breast cancer surgical volume in the world are its distinguishing contributions, with Yi-Zhou Jiang, Xichun Hu and Dingwei Ye also listed. Nuclide links it to triple-negative breast cancer, to TROP2 as a target and TROP2 PET as a technology, and to Zhongshan Hospital and the Chinese Society of Clinical Oncology. Whether subtype-directed treatment of TNBC improves on a single standard is the question FUTURE was designed to answer. Its TNBC, TROP2 PET and surgery programmes are listed below.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Shanghai_Cancer_Center","links":[{"label":"Official website","url":"https://www.shca.org.cn"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":["ga-68"],"indications":[],"sections":[],"technologies":["trop2-pet"],"targets":["trop2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["song-shaoli"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Shanghai","country":"CN","lat":31.191,"lng":121.437,"institutionType":"cancer-center","website":"https://www.shca.org.cn","newsweekOncology2026":55,"programs":["TNBC subtyping (FUTURE trial)","TROP2 PET","Breast surgery"],"route":"/institutions/fuscc/"}
{"id":"heidelberg-nct","kind":"institution","name":"Heidelberg University Hospital / NCT / DKFZ","aka":[],"tldr":"Heidelberg is Germany's cancer research capital, home to the DKFZ (largest cancer research institute in Germany) and the NCT, and the birthplace of FAPI PET and the brain tumour methylation classifier.","summary":"Heidelberg University Hospital, with the National Center for Tumor Diseases and the German Cancer Research Center (DKFZ), is Germany's cancer research capital and ranks eighteenth in the Newsweek/Statista oncology list. Its record includes the FAPI PET tracers from Haberkorn, Giesel and Kratochwil, the first-in-human actinium-225 PSMA therapy, the Heidelberg Ion-Beam Therapy Center for carbon ions, the DKFZ brain tumour methylation classifier from Pfister and von Deimling, and the MASTER precision oncology programme, with Stefan Fröhling among its leaders. Nuclide links it to FAP and PSMA as targets, to SOFIE Biosciences, to the first vaccine trial against shared neoantigens of mismatch-repair-deficient cancers, and to ideas for a university cyclotron network and core-funded radiotherapy trials. Turning tracers into approved therapies at scale is the open problem. The DKFZ has its own page.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.nct-heidelberg.de"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":["fapi-pet","targeted-alpha-therapy"],"targets":["fap","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["clemens-kratochwil","frederik-giesel","uwe-haberkorn"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Heidelberg","country":"DE","lat":49.417,"lng":8.67,"institutionType":"cancer-center","website":"https://www.nct-heidelberg.de","newsweekOncology2026":18,"university":"Heidelberg University","programs":["FAPI PET","Alpha PSMA therapy","Carbon-ion therapy","CNS methylation classifier","DKFZ basic research"],"route":"/institutions/heidelberg-nct/"}
{"id":"iaea","kind":"institution","name":"International Atomic Energy Agency: Rays of Hope","aka":["IAEA","Rays of Hope","PACT"],"tldr":"The UN nuclear agency's programme to bring radiotherapy and nuclear medicine to the dozens of countries that have no or too few treatment machines.","summary":"The IAEA has supported radiotherapy and nuclear medicine in member states for decades through technical cooperation, dosimetry audits and the Human Health Programme, and in 2022 launched Rays of Hope to close the gap in countries where most cancer patients who need radiotherapy cannot get it. Rays of Hope funds equipment, training and quality assurance, working first in African countries with no linear accelerators, and creates Anchor Centres of expertise. The agency's Programme of Action for Cancer Therapy (PACT) runs imPACT reviews of national cancer control capacity with WHO and IARC, and its Dosimetry Laboratory underpins radiotherapy calibration worldwide. The IAEA also supports radiopharmaceutical production capacity for theranostics.","asOf":"2026-09-09","links":[{"label":"Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"},{"label":"IAEA cancer","url":"https://www.iaea.org/topics/cancer"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":["rafael-mariano-grossi"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Vienna","country":"AT","lat":48.234,"lng":16.416,"institutionType":"government","website":"https://www.iaea.org/services/rays-of-hope","programs":["Rays of Hope (radiotherapy access)","imPACT reviews (with WHO and IARC)","Dosimetry and quality audit services","Radiopharmaceutical capacity building"],"route":"/institutions/iaea/"}
{"id":"ico-angers-nantes","kind":"institution","name":"Institut de Cancérologie de l'Ouest (ICO)","aka":["ICO Paul Papin","ICO René Gauducheau","Integrated Center for Oncology"],"tldr":"The Unicancer cancer centre for western France, with sites in Angers and Nantes, accredited by OECI as a Comprehensive Cancer Centre.","summary":"The Institut de Cancérologie de l'Ouest was created by merging the Centre Paul Papin in Angers and the Centre René Gauducheau in Saint-Herblain near Nantes, and is one of the 18 Centres de Lutte Contre le Cancer of the Unicancer network. It delivers surgery, radiotherapy, medical oncology and nuclear medicine across the Pays de la Loire, hosts an early-phase trials unit, and works with the universities of Angers and Nantes and Inserm on radiopharmaceuticals, alpha-emitter therapy and immuno-oncology, drawing on the Nantes nuclear medicine and cyclotron infrastructure. The ICO is accredited by the Organisation of European Cancer Institutes as a Comprehensive Cancer Centre.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.institut-cancerologie-ouest.com"}],"tags":["oeci-accredited","oeci-comprehensive-cancer-centre","unicancer"],"related":[],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Angers","country":"FR","lat":47.478,"lng":-0.563,"institutionType":"cancer-center","website":"https://www.institut-cancerologie-ouest.com","programs":["Radiopharmaceuticals and alpha therapy","Early-phase trials","Radiotherapy"],"route":"/institutions/ico-angers-nantes/"}
{"id":"inselspital-bern","kind":"institution","name":"Inselspital, Bern University Hospital / University Cancer Center Inselspital","aka":["Inselspital","UCI Bern","Bern Center for Precision Medicine"],"tldr":"Bern's university hospital, a high-volume radioligand therapy centre and home to the Bern Center for Precision Medicine and the SAKK trial group.","summary":"The University Cancer Center Inselspital coordinates cancer care at Switzerland's capital university hospital. Its nuclear medicine department under Axel Rominger is one of Europe's largest PSMA and somatostatin-receptor radioligand therapy centres with a strong dosimetry programme, and Mark Rubin, co-discoverer of the TMPRSS2-ERG fusion in prostate cancer, directs the Department for BioMedical Research and the Bern Center for Precision Medicine. The hospital runs neuro-oncology and neurosurgery, thoracic and gastrointestinal surgery, haematology and CAR-T, and is a lead site for the Swiss Group for Clinical Cancer Research (SAKK), whose coordinating centre is in Bern. The Insel Gruppe covers a large catchment across the Bernese region.","asOf":"2026-09-09","links":[{"label":"Tumorzentrum Inselspital","url":"https://www.tumorzentrum.insel.ch"},{"label":"Bern Center for Precision Medicine","url":"https://www.bcpm.unibe.ch"},{"label":"SAKK","url":"https://www.sakk.ch"}],"tags":[],"related":[],"indications":["prostate","neuroendocrine","glioblastoma"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma","sstr2"],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":["usz-zurich"],"pathways":[],"terms":["dosimetry","theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Bern","country":"CH","lat":46.948,"lng":7.423,"institutionType":"hospital","website":"https://www.tumorzentrum.insel.ch","university":"Universität Bern","programs":["Radioligand therapy and dosimetry","Bern Center for Precision Medicine","Prostate cancer genomics","Neuro-oncology","SAKK trials"],"route":"/institutions/inselspital-bern/"}
{"id":"institut-jules-bordet","kind":"institution","name":"Institut Jules Bordet","aka":["Jules Bordet Institute","Bordet","Hôpital Universitaire de Bruxelles"],"tldr":"Belgium's only hospital devoted entirely to cancer, birthplace of the Breast International Group and a world centre for breast cancer trials.","summary":"The Institut Jules Bordet opened in 1939, named after the Nobel laureate immunologist Jules Bordet, and moved to a new building beside Erasme Hospital in Anderlecht in 2021 as part of the Hôpital Universitaire de Bruxelles. It is OECI-accredited as a comprehensive cancer centre. Martine Piccart co-founded the Breast International Group here and led the HERA trial of adjuvant trastuzumab; Christos Sotiriou's laboratory developed gene expression signatures for breast cancer and Michail Ignatiadis leads circulating tumour DNA studies, while Ahmad Awada's early-phase unit tests new agents. Bordet is also strong in haematology, nuclear medicine and surgical oncology, and Brussels hosts both BIG and EORTC headquarters.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Institut_Jules_Bordet","links":[{"label":"Homepage","url":"https://www.bordet.be"},{"label":"Breast International Group","url":"https://www.bigagainstbreastcancer.org"}],"tags":[],"related":[],"indications":["breast-her2-positive","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Brussels","country":"BE","lat":50.813,"lng":4.265,"institutionType":"cancer-center","website":"https://www.bordet.be","university":"Université libre de Bruxelles","programs":["Breast International Group","Breast cancer genomics and ctDNA","Early-phase trials","Haematology","Nuclear medicine"],"route":"/institutions/institut-jules-bordet/"}
{"id":"iov-veneto","kind":"institution","name":"Istituto Oncologico Veneto IRCCS","aka":["IOV","Veneto Institute of Oncology"],"tldr":"The Veneto region's OECI-accredited comprehensive cancer centre in Padua, strong in breast cancer trials, melanoma and tumour immunology.","summary":"Founded in 2005, the Istituto Oncologico Veneto is the IRCCS cancer institute of the Veneto region and coordinates the regional oncology network; it is accredited by the OECI as a comprehensive cancer centre. Pierfranco Conte and Valentina Guarneri's breast oncology group led the ShortHER trial of trastuzumab duration and many neoadjuvant studies, the melanoma unit is a leading Italian immunotherapy trial site, and Vincenzo Bronte's immunology programme is known for myeloid-derived suppressor cells. The institute runs gastrointestinal, thoracic and gynaecological oncology, radiotherapy and nuclear medicine across Padua and Castelfranco Veneto, with a phase 1 unit and the University of Padua's oncology school.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.ioveneto.it"},{"label":"Research","url":"https://www.ioveneto.it/ricerca/"}],"tags":[],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Padua","country":"IT","lat":45.407,"lng":11.894,"institutionType":"cancer-center","website":"https://www.ioveneto.it","university":"Università degli Studi di Padova","programs":["Breast cancer trials","Melanoma immunotherapy","Tumour immunology (myeloid cells)","Veneto oncology network","Phase 1 unit"],"route":"/institutions/iov-veneto/"}
{"id":"irst-meldola","kind":"institution","name":"IRCCS Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori' (IRST)","aka":["IRST Meldola","IRST IRCCS"],"tldr":"The Romagna cancer institute, known for radioligand therapy, nuclear medicine and genitourinary and sarcoma trials.","summary":"IRST opened in 2007 in Meldola near Forlì as the cancer research institute for the Romagna area of Emilia-Romagna and was named after its founder, the oncologist Dino Amadori. Its nuclear medicine department under Giovanni Paganelli, a pioneer of peptide receptor radionuclide therapy with yttrium-90 and lutetium-177 DOTATOC, is one of Italy's leading radioligand therapy centres, and Ugo De Giorgi's genitourinary and sarcoma unit runs PSMA and immunotherapy trials. The institute has an osteoncology and rare tumour centre, a bioscience laboratory for genomics and liquid biopsy, and an early-phase unit, and delivers medical oncology across the Romagna hospital network.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.irst.emr.it"}],"tags":[],"related":["lu-177","y-90"],"indications":["neuroendocrine","prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["sstr2","psma"],"drugs":["lutathera","pluvicto"],"companies":[],"institutions":["sant-orsola-bologna"],"pathways":[],"terms":["theranostics","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Meldola","country":"IT","lat":44.129,"lng":12.061,"institutionType":"cancer-center","website":"https://www.irst.emr.it","university":"Università di Bologna","programs":["Radioligand therapy and nuclear medicine","Genitourinary oncology","Osteoncology and rare tumours","Liquid biopsy laboratory"],"route":"/institutions/irst-meldola/"}
{"id":"ivo-valencia","kind":"institution","name":"Fundación Instituto Valenciano de Oncología (IVO)","aka":["IVO"],"tldr":"A private non-profit dedicated cancer hospital in Valencia, accredited by OECI as a Cancer Centre.","summary":"The Instituto Valenciano de Oncología is a non-profit foundation hospital devoted entirely to cancer, providing surgical oncology, medical oncology, radiation oncology, nuclear medicine, diagnostic imaging and pathology for patients from the Valencian Community and beyond under agreements with the public health system. It runs a clinical trials unit and research programmes in breast, urological and gastrointestinal cancers, radiotherapy techniques and hereditary cancer, and is accredited by the Organisation of European Cancer Institutes as a Cancer Centre.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.ivo.es"}],"tags":["oeci-accredited","oeci-cancer-centre"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["la-fe-valencia"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Valencia","country":"ES","lat":39.481,"lng":-0.389,"institutionType":"cancer-center","website":"https://www.ivo.es","programs":["Dedicated cancer hospital","Radiation oncology","Clinical trials unit"],"route":"/institutions/ivo-valencia/"}
{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","aka":[],"tldr":"Johns Hopkins is the birthplace of cancer genomics (Vogelstein), MSI-high immunotherapy (Le, Diaz), and liquid biopsy and MCED science (CancerSEEK).","summary":"Johns Hopkins Hospital and its Sidney Kimmel Comprehensive Cancer Center in Baltimore are where cancer genomics began with Vogelstein and Kinzler, and the centre holds NCI comprehensive designation and tenth place in the Newsweek/Statista oncology ranking. Its record includes pembrolizumab in mismatch-repair-deficient tumours, the first tumour-agnostic approval, led by Le and Diaz, the CancerSEEK liquid biopsy that fed Exact Sciences' multi-cancer early detection programme, and the Bloomberg-Kimmel Institute for Cancer Immunotherapy under Drew M. Pardoll and Elizabeth M. Jaffee. Nuclide links it to DELFI Diagnostics, to the DETECT-A, DYNAMIC and CheckMate 816 papers, and to pathways from epigenetic reprogramming to telomere maintenance. Whether blood-based early detection lowers harm as well as finding cancers is the question its own work posed. Programmes and people are listed below.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.hopkinsmedicine.org/kimmel-cancer-center"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Baltimore","country":"US","lat":39.297,"lng":-76.593,"institutionType":"cancer-center","website":"https://www.hopkinsmedicine.org/kimmel-cancer-center","nci":"comprehensive","newsweekOncology2026":10,"university":"Johns Hopkins University","programs":["Cancer genomics","MSI-H immunotherapy","Liquid biopsy / MCED","Bloomberg-Kimmel Immunotherapy"],"route":"/institutions/johns-hopkins/"}
{"id":"karolinska","kind":"institution","name":"Karolinska University Hospital","aka":["Karolinska Comprehensive Cancer Center"],"tldr":"Sweden's leading cancer hospital, linked to the Karolinska Institutet and Nobel Assembly, with strong registry-based research.","summary":"Karolinska University Hospital in Stockholm is Sweden's leading cancer hospital, linked to the Karolinska Institutet and the Nobel Assembly, and ranks thirty-ninth in the Newsweek/Statista oncology list. Its Comprehensive Cancer Centre is known for registry-based research, because Sweden's national quality registries make real-world evidence and registry-randomised trials possible, and it collaborates with the Skandion proton clinic in Uppsala; Per Hall, Jonas Bergh and Thomas Helleday are among the people Nuclide lists. Nuclide links it to the ALASCCA aspirin trial, to the Swedish registry study of HPV vaccination and cervical cancer, and to ideas on randomising inside cancer registries and a registry-based MCED trial. Whether registry designs can carry regulatory weight outside the Nordics is the open question. Its registry and haematology programmes are listed below.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Karolinska_University_Hospital","links":[{"label":"Official website","url":"https://www.karolinska.se"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Stockholm","country":"SE","lat":59.35,"lng":18.034,"institutionType":"university","website":"https://www.karolinska.se","newsweekOncology2026":39,"university":"Karolinska Institutet","programs":["Registry research","Haematology"],"route":"/institutions/karolinska/"}
{"id":"kfshrc","kind":"institution","name":"King Faisal Specialist Hospital and Research Centre","aka":["KFSH&RC","KFSHRC","مستشفى الملك فيصل التخصصي"],"tldr":"Saudi Arabia's flagship tertiary hospital, whose Oncology Centre runs the Gulf's largest transplant, CAR-T and proton therapy programmes.","summary":"King Faisal Specialist Hospital and Research Centre opened in Riyadh in 1975 and, with campuses in Jeddah and Madinah, is the leading referral hospital of Saudi Arabia and the wider Gulf. Its Oncology Centre and King Fahad National Centre for Children's Cancer deliver high-volume adult and paediatric cancer care, including one of the largest haematopoietic stem cell transplant programmes in the region, locally manufactured CAR-T therapy, robotic surgery, radioligand therapy and the first proton therapy facility in the Middle East, opened in Riyadh. The Research Centre hosts genomics under the Saudi Human Genome Program, cancer biology and clinical trials units, and the hospital houses the Saudi Cancer Registry's largest contributing service and pioneering work on thyroid, breast and hereditary cancers common in the Kingdom.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/King_Faisal_Specialist_Hospital_and_Research_Centre","links":[{"label":"KFSH&RC","url":"https://www.kfshrc.edu.sa"}],"tags":[],"related":[],"indications":["thyroid","dlbcl"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Riyadh","country":"SA","lat":24.69,"lng":46.674,"institutionType":"hospital","website":"https://www.kfshrc.edu.sa","programs":["Oncology Centre and children's cancer centre","Stem cell transplant and CAR-T","Proton therapy","Saudi Human Genome Program"],"route":"/institutions/kfshrc/"}
{"id":"la-fe-valencia","kind":"institution","name":"Hospital Universitari i Politècnic La Fe","aka":["Hospital La Fe","IIS La Fe"],"tldr":"Valencia's flagship public hospital, with a haematology department that shaped the treatment of acute promyelocytic leukaemia through the PETHEMA group.","summary":"La Fe is the largest hospital complex of the Valencian region and hosts the IIS La Fe research institute. Its haematology department, long led by Miguel Ángel Sanz, designed the PETHEMA protocols that established risk-adapted all-trans retinoic acid and anthracycline therapy for acute promyelocytic leukaemia and remains a reference for acute leukaemias and transplantation within Spain's PETHEMA cooperative group. The hospital runs a large medical oncology service, paediatric oncology, radiotherapy including stereotactic programmes, a nuclear medicine and PET unit and an early-phase trials unit. It is a regional hub for molecular diagnostics and hereditary cancer counselling.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.lafe.san.gva.es"},{"label":"IIS La Fe","url":"https://www.iislafe.es"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Valencia","country":"ES","lat":39.443,"lng":-0.376,"institutionType":"hospital","website":"https://www.lafe.san.gva.es","university":"Universitat de València","programs":["Acute leukaemia (PETHEMA)","Transplantation","Paediatric oncology","Radiotherapy","Molecular diagnostics"],"route":"/institutions/la-fe-valencia/"}
{"id":"lmu-munich","kind":"institution","name":"LMU Klinikum München","aka":[],"tldr":"LMU Klinikum is Munich's university cancer centre, with strengths in PSMA theranostics and haematology.","summary":"LMU Klinikum München is the university hospital of Ludwig-Maximilians-Universität and, with TUM, forms the Comprehensive Cancer Center Munich; it ranks thirty-first in the Newsweek/Statista World's Best Specialized Hospitals list for oncology. Its nuclear medicine leadership in PSMA imaging and radioligand therapy is the reason it appears on theranostics pages, and haematology is its other declared strength, with Peter Bartenstein, Michael von Bergwelt, Martin Dreyling, Nadia Harbeck, Volker Heinemann and Claus Belka among the people Nuclide lists. Nuclide links it to PSMA PET, to the European Association of Nuclear Medicine and Deutsche Krebshilfe, and to its partner TUM Klinikum rechts der Isar. How theranostics scales from a few academic centres to routine care is the open question. Its theranostics and haematology programmes are listed below.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.lmu-klinikum.de"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["peter-bartenstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Munich","country":"DE","lat":48.11,"lng":11.47,"institutionType":"university","website":"https://www.lmu-klinikum.de","newsweekOncology2026":31,"university":"Ludwig-Maximilians-Universität","programs":["Theranostics","Haematology"],"route":"/institutions/lmu-munich/"}
{"id":"mayo-clinic","kind":"institution","name":"Mayo Clinic","aka":[],"tldr":"Consistently the top-ranked US hospital overall, with strong proton therapy and the first US carbon-ion centre under construction.","summary":"Mayo Clinic, headquartered in Rochester, Minnesota, is consistently the top-ranked US hospital overall and holds NCI comprehensive designation through the Mayo Clinic Comprehensive Cancer Center, which spans Rochester, Phoenix and Jacksonville; it sits fifth in the Newsweek/Statista oncology ranking. Its cancer strengths are multiple myeloma, lymphoma and individualised medicine, with proton therapy and the first US carbon-ion facility under construction in Jacksonville. Nuclide links it to the Atlas pathology model built with Aignostics and Charité, to liver transplantation for cancer, to senescence and JAK-STAT pathway work, and to people including S. Vincent Rajkumar, Shaji K. Kumar and Matthew P. Goetz. Whether carbon-ion therapy earns its cost against protons is the open question its new centre will help answer. The Arizona and Florida campuses have their own Nuclide pages.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Mayo_Clinic","links":[{"label":"Official website","url":"https://www.mayoclinic.org"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oliver-sartor"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Rochester, MN","country":"US","lat":44.022,"lng":-92.467,"institutionType":"hospital","website":"https://www.mayoclinic.org","nci":"comprehensive","newsweekOncology2026":5,"programs":["Carbon-ion therapy (Jacksonville)","Myeloma","Proton therapy"],"route":"/institutions/mayo-clinic/"}
{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","aka":[],"tldr":"MD Anderson is the largest cancer centre in the world by patient volume, with the biggest phase 1 programme and a leading CAR-NK effort.","summary":"MD Anderson Cancer Center in Houston, part of the University of Texas and founded in 1941, is the largest cancer centre in the world by patient volume and holds NCI comprehensive designation and second place in the Newsweek/Statista oncology ranking. It runs the biggest early-phase trial unit anywhere, the Moon Shots programme, a proton therapy centre and a leading CAR-NK effort with Takeda, and its breast group under Symmans defined the Residual Cancer Burden index used to grade response after neoadjuvant treatment. Nuclide links it to LACC in cervical cancer and the ROAR anaplastic thyroid cohort, to work on the gut microbiome and dietary fibre in immunotherapy response, and to pathways from cancer neuroscience to cachexia. Whether its scale translates into faster answers than smaller centres remains a fair question. The people listed here show who leads which programme.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/MD_Anderson_Cancer_Center","links":[{"label":"Official website","url":"https://www.mdanderson.org"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Houston","country":"US","lat":29.707,"lng":-95.397,"institutionType":"cancer-center","website":"https://www.mdanderson.org","nci":"comprehensive","newsweekOncology2026":2,"university":"University of Texas","programs":["Phase 1 trials","CAR-NK","Residual Cancer Burden index","Proton therapy","Moon Shots"],"route":"/institutions/md-anderson/"}
{"id":"mhra","kind":"institution","name":"Medicines and Healthcare products Regulatory Agency","aka":["MHRA"],"tldr":"The UK medicines and devices regulator, which since Brexit runs its own approvals, joins Project Orbis and uses international reliance routes to speed cancer drug access.","summary":"Formed in 2003 by merging the Medicines Control Agency and the Medical Devices Agency, the MHRA became the UK's standalone regulator for new medicines after the UK left the EU in 2021. It participates in the FDA-led Project Orbis and the Access Consortium (with Australia, Canada, Singapore and Switzerland), uses the International Recognition Procedure to rely on approvals by trusted regulators, and runs the Innovative Licensing and Access Pathway with NICE and the Scottish Medicines Consortium to align licensing and reimbursement. The MHRA also regulates clinical trials, devices including AI software, and blood and tissue products, and operates the Yellow Card safety scheme.","asOf":"2026-09-09","links":[{"label":"MHRA","url":"https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"London","country":"GB","lat":51.503,"lng":-0.02,"institutionType":"government","website":"https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency","programs":["Project Orbis and Access Consortium","International Recognition Procedure","Innovative Licensing and Access Pathway (with NICE and SMC)","Clinical trials and device regulation"],"route":"/institutions/mhra/"}
{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","aka":[],"tldr":"The world's top-ranked cancer hospital, home of MSK-IMPACT sequencing, the dostarlimab rectal cancer study, and CAR-T pioneers.","summary":"Memorial Sloan Kettering Cancer Center is a New York cancer centre founded in 1884, NCI-designated as comprehensive and ranked first in the Newsweek/Statista World's Best Specialized Hospitals list for oncology, which makes it the reference point against which other cancer hospitals are measured. Its firsts include MSK-IMPACT, an FDA-authorised tumour sequencing panel that feeds OncoKB and cBioPortal, co-development of CD19 CAR-T cell therapy with Sadelain's group, the dostarlimab study in mismatch-repair-deficient rectal cancer led by Andrea Cercek, and the Paige AI digital pathology spin-out. It runs one of the largest oncology trial portfolios in the United States. The open question for a centre this large is how quickly its knowledge reaches practice elsewhere, a bottleneck Nuclide tracks explicitly. Its people and trials pages are the best way into the detail.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Memorial_Sloan_Kettering_Cancer_Center","links":[{"label":"Official website","url":"https://www.mskcc.org"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jason-lewis","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"New York","country":"US","lat":40.764,"lng":-73.956,"institutionType":"cancer-center","website":"https://www.mskcc.org","nci":"comprehensive","newsweekOncology2026":1,"programs":["MSK-IMPACT / OncoKB","CAR-T (Sadelain)","dMMR rectal organ preservation","Paige AI","Radiopharmaceutical development"],"route":"/institutions/mskcc/"}
{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","aka":[],"tldr":"The NCI is the US government's cancer research agency, spending ~$7B a year and running the Cancer Centers Program, TCGA, and Rosenberg's cell therapy lab.","summary":"The National Cancer Institute, part of the US National Institutes of Health in Bethesda, is the US government's cancer research agency; it runs the Cancer Centers Program that designates seventy-four centres, The Cancer Genome Atlas and its Genomic Data Commons, the RAS Initiative, the SEER registry and the cooperative groups NRG, SWOG, Alliance and ECOG-ACRIN. Its Surgery Branch under Rosenberg developed tumour-infiltrating lymphocyte therapy and neoantigen TCR-T, and its Pediatric MATCH and myeloMATCH trials, its CPTAC and PDQ resources and the JNCI journal all sit in Nuclide. It is linked to bottlenecks on data silos, hidden failures, funding that follows fashion and slow translation, and to ideas for a national non-profit CRO and perpetual platform trials. Whether it can fund infrastructure rather than projects is the standing question. Douglas R. Lowy is among the people listed. The institutions linked below are the NCI-designated cancer centres in Nuclide, its intramural Center for Cancer Research and the Frederick National Laboratory; the trials are those whose sponsor field names the NCI.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.cancer.gov"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber","johns-hopkins","mayo-clinic","md-anderson","mskcc","penn-abramson","ucla-jonsson","ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Bethesda, MD","country":"US","lat":39.003,"lng":-77.104,"institutionType":"government","website":"https://www.cancer.gov","programs":["Cancer Centers Program (74 centres)","TCGA / GDC","Cooperative groups","Surgery Branch cell therapy"],"route":"/institutions/nci/"}
{"id":"nct-dresden","kind":"institution","name":"NCT/UCC Dresden, University Hospital Carl Gustav Carus","aka":["National Center for Tumor Diseases Dresden","University Cancer Center Dresden","OncoRay","National Cancer Center Dresden","NCT Dresden"],"tldr":"The second National Center for Tumor Diseases site, known for proton therapy research at OncoRay and AI in pathology and surgery.","summary":"NCT/UCC Dresden was founded in 2015 as a partnership between the DKFZ, the University Hospital Carl Gustav Carus, TU Dresden's medical faculty and the Helmholtz-Zentrum Dresden-Rossendorf. The OncoRay centre and the University Proton Therapy Dresden facility (treating since 2014) pursue biologically adapted, image-guided and laser-driven particle therapy; the DKFZ's chairman Michael Baumann previously directed radiation oncology there. The Else Kröner Fresenius Center for Digital Health hosts groups such as Jakob Nikolas Kather's on deep learning in pathology, and the hospital's surgical oncology programme develops AI-assisted surgery. Clinical strengths include haematology and transplantation, gastrointestinal surgery and precision oncology through a DKTK-wide molecular tumour board.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.nct-dresden.de"},{"label":"OncoRay","url":"https://www.oncoray.de"},{"label":"EKFZ for Digital Health","url":"https://digitalhealth.tu-dresden.de"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Dresden","country":"DE","lat":51.056,"lng":13.78,"institutionType":"cancer-center","website":"https://www.nct-dresden.de","university":"Technische Universität Dresden","programs":["OncoRay and proton therapy","Digital health and computational pathology","Haematology","Surgical oncology","Precision oncology (DKTK MASTER)"],"route":"/institutions/nct-dresden/"}
{"id":"oslo-radium-hospital","kind":"institution","name":"Oslo University Hospital, The Norwegian Radium Hospital","aka":["Radiumhospitalet","Institute for Cancer Research Oslo","OUS"],"tldr":"Norway's national cancer hospital and research institute, where the alpha emitter radium-223 (Xofigo) and Photocure's bladder imaging agent were born.","summary":"The Norwegian Radium Hospital opened in 1932 as Norway's specialist cancer hospital and became part of Oslo University Hospital in 2009; its Institute for Cancer Research dates from 1954 and is a European reference for cancer genomics, immunology and radiation biology. Roy Larsen and Øyvind Bruland developed radium-223 there and founded Algeta, whose Xofigo became the first approved targeted alpha therapy after Bayer's acquisition, and the hospital also spun out Photocure and Ultimovacs. Current groups include Johanna Olweus on T-cell receptor therapies, Ragnhild Lothe on colorectal genomics, Ola Myklebost on sarcoma and Åslaug Helland, who leads the national IMPRESS-Norway precision medicine trial. The campus is being rebuilt with a new clinic and Norway's first proton therapy centre, and it anchors the Oslo Cancer Cluster innovation park.","asOf":"2026-09-09","links":[{"label":"Institute for Cancer Research","url":"https://www.ous-research.no/institute/"},{"label":"Oslo University Hospital","url":"https://www.oslo-universitetssykehus.no"},{"label":"Oslo Cancer Cluster","url":"https://oslocancercluster.no"}],"tags":[],"related":["ra-223"],"indications":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":["bayer"],"institutions":["karolinska"],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Oslo","country":"NO","lat":59.933,"lng":10.66,"institutionType":"cancer-center","website":"https://www.ous-research.no/institute/","university":"University of Oslo","programs":["Institute for Cancer Research","Targeted alpha therapy heritage (radium-223)","IMPRESS-Norway precision medicine","Sarcoma and rare cancers","Proton therapy centre"],"route":"/institutions/oslo-radium-hospital/"}
{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","aka":[],"tldr":"Where CAR-T became a drug (June, Levine; Emily Whitehead), mRNA was made druggable (Karikó, Weissman), and PARP PET was invented.","summary":"The Abramson Cancer Center at the University of Pennsylvania in Philadelphia, NCI-designated as comprehensive, is where CAR-T became a drug through Carl H. June, Bruce L. Levine and the treatment of Emily Whitehead, where Karikó and Drew Weissman made mRNA druggable, recognised by the 2023 Nobel Prize, and where PARP PET was invented. Its record covers CTL019, now tisagenlecleucel, proved in ELIANA and JULIET, the in vivo CAR-T origins behind Capstan and Interius BioTherapeutics, 18F-FluorThanatrace PARP PET, proton therapy and the Basser Center for BRCA, with Robert H. Vonderheide and Robert H. Mach among its people. Nuclide links it to CAR-T for glioma, to the PROSE paper on preventive surgery in BRCA carriers, and to Children's Hospital of Philadelphia. Whether in vivo CAR-T can match ex vivo products is the question its spin-outs now test. Programmes are listed below.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.pennmedicine.org/cancer"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["parp-pet"],"targets":["parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-mach"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Philadelphia","country":"US","lat":39.949,"lng":-75.194,"institutionType":"cancer-center","website":"https://www.pennmedicine.org/cancer","nci":"comprehensive","university":"University of Pennsylvania","programs":["CAR-T and in vivo CAR","mRNA","PARP PET","BRCA (Basser Center)"],"route":"/institutions/penn-abramson/"}
{"id":"peter-mac","kind":"institution","name":"Peter MacCallum Cancer Centre","aka":[],"tldr":"Peter Mac is Australia's only dedicated cancer hospital and a leader in theranostics, CAR-T, and radiation oncology.","summary":"Peter MacCallum Cancer Centre in Melbourne is Australia's only dedicated cancer hospital, the core of the Victorian Comprehensive Cancer Centre, and ranks fourteenth in the Newsweek/Statista oncology list. It pioneered PSMA PET imaging and lutetium-177 PSMA radioligand therapy through Hofman's TheraP and proPSMA trials, became Australia's first CAR-T centre, and has a strong radiation oncology programme, with Sarah-Jane Dawson, Joseph Trapani, Declan G. Murphy, Andrew H. Wei and Grant McArthur among its people. Nuclide links it to prostate cancer, to the CROWN and DYNAMIC papers, to ANZUP and other Australian trial groups, and to ideas for a rapid research autopsy network and a shared cyclotron network for new tracers. Getting radioligand supply and regulation to match demand is the open problem its theranostics work exposes. Its trial and people pages carry the detail.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Peter_MacCallum_Cancer_Centre","links":[{"label":"Official website","url":"https://www.petermac.org"}],"tags":[],"related":["lu-177"],"indications":[],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["declan-murphy","hofman-michael","sandhu-shahneen"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Melbourne","country":"AU","lat":-37.799,"lng":144.956,"institutionType":"cancer-center","website":"https://www.petermac.org","newsweekOncology2026":14,"programs":["PSMA theranostics (TheraP, proPSMA)","CAR-T","Radiation oncology"],"route":"/institutions/peter-mac/"}
{"id":"pla-general-hospital","kind":"institution","name":"Chinese PLA General Hospital","aka":["301 Hospital","解放军总医院"],"tldr":"China's military flagship hospital, known in oncology for early CAR-T and gene-edited T-cell trials, minimally invasive liver surgery and nuclear medicine.","summary":"The Chinese PLA General Hospital, commonly called 301 Hospital, is the largest military hospital in China and a comprehensive tertiary centre in Beijing. Its Department of Bio-therapeutics under Weidong Han ran some of the earliest Chinese CAR-T and CRISPR-edited T-cell studies in lymphoma and solid tumours, and its haematology, hepatobiliary surgery (including laparoscopic and robotic hepatectomy), urology and interventional radiology departments are national leaders. The hospital has a large PET/CT and nuclear medicine service and serves as a national referral centre for complex cases from across China.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/People's_Liberation_Army_General_Hospital_and_Medical_School","links":[{"label":"Chinese PLA General Hospital","url":"https://www.301hospital.com.cn"}],"tags":[],"related":[],"indications":["dlbcl","hcc","prostate"],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Beijing","country":"CN","lat":39.907,"lng":116.283,"institutionType":"hospital","website":"https://www.301hospital.com.cn","programs":["CAR-T and gene-edited T-cell trials","Hepatobiliary and robotic surgery","Nuclear medicine","Haematology"],"route":"/institutions/pla-general-hospital/"}
{"id":"pmda","kind":"institution","name":"Pharmaceuticals and Medical Devices Agency","aka":["PMDA","独立行政法人医薬品医療機器総合機構"],"tldr":"Japan's drug and device review agency, which works with the health ministry to approve cancer drugs and has largely closed the historical 'drug lag' with the US and Europe.","summary":"Established in 2004, the PMDA conducts scientific review of new drugs, devices and regenerative medicine products, with final approval by the Ministry of Health, Labour and Welfare. It introduced the SAKIGAKE fast-track designation, conditional early approval for regenerative medicines, and the Orphan and Conditional approval pathways, and it has been a full participant in ICH harmonisation. Japan approved many antibody-drug conjugates and targeted lung cancer agents at or near the same time as the FDA, and its requirements for Japanese patient data shaped global trial designs. The PMDA also runs post-marketing safety surveillance and the relief system for adverse drug reactions.","asOf":"2026-09-09","links":[{"label":"PMDA","url":"https://www.pmda.go.jp/english/"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Tokyo","country":"JP","lat":35.674,"lng":139.762,"institutionType":"government","website":"https://www.pmda.go.jp/english/","programs":["New drug and device review","SAKIGAKE designation","Conditional and time-limited approval for regenerative medicine","Post-marketing safety"],"route":"/institutions/pmda/"}
{"id":"qst-hospital","kind":"institution","name":"QST Hospital (National Institutes for Quantum Science and Technology)","aka":["NIRS Hospital","HIMAC","QST病院"],"tldr":"The world's first carbon-ion therapy hospital (HIMAC, 1994), which established the clinical evidence base for heavy-ion radiotherapy.","summary":"QST Hospital, formerly the National Institute of Radiological Sciences hospital, began treating patients with carbon ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in 1994, the first dedicated medical heavy-ion facility. Over three decades it has treated more carbon-ion patients than any other centre, developed hypofractionated protocols for prostate, lung, liver, pancreatic, bone and soft-tissue sarcoma and head and neck tumours, and pioneered scanning beam delivery, respiratory gating and the rotating gantry now used in newer facilities. The institute leads Japan's quantum-scanning carbon-ion programme, radiopharmaceutical research including astatine-211 targeted alpha therapy, and international training for centres in Europe and Asia.","asOf":"2026-09-09","links":[{"label":"QST Hospital (page moved; nearest live section)","url":"https://www.qst.go.jp/"},{"label":"QST","url":"https://www.qst.go.jp/site/qst-english/"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":[],"related":["at-211"],"indications":["prostate","hcc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Chiba","country":"JP","lat":35.634,"lng":140.104,"institutionType":"research-institute","website":"https://www.qst.go.jp/","programs":["Carbon-ion therapy (HIMAC)","Compact carbon-ion technology","Astatine-211 alpha therapy","Radiation biology"],"route":"/institutions/qst-hospital/"}
{"id":"radboudumc","kind":"institution","name":"Radboudumc Centre for Oncology","aka":["Radboud University Medical Center"],"tldr":"The university hospital of Nijmegen, a leading Dutch centre for prostate imaging, dendritic cell vaccines and tumour immunology, currently in OECI accreditation.","summary":"Radboud University Medical Center is the academic hospital of Radboud University and a tertiary cancer centre for the east of the Netherlands. Its Centre for Oncology integrates medical oncology, radiotherapy, haematology, surgical oncology and urology, and its research is internationally recognised in prostate MRI and PSMA imaging, dendritic cell vaccination and tumour immunology (Radboud Institute for Molecular Life Sciences), hereditary cancer, and hepatobiliary and pancreatic surgery. Radboudumc is listed by the Organisation of European Cancer Institutes as in accreditation.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.radboudumc.nl"}],"tags":["oeci-in-accreditation"],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Nijmegen","country":"NL","lat":51.824,"lng":5.86,"institutionType":"hospital","website":"https://www.radboudumc.nl","university":"Radboud University","programs":["Prostate imaging and PSMA","Dendritic cell vaccines","Tumour immunology","Hereditary cancer"],"route":"/institutions/radboudumc/"}
{"id":"royal-marsden","kind":"institution","name":"The Royal Marsden","aka":[],"tldr":"The Royal Marsden was the world's first hospital dedicated to cancer (1851) and is paired with the Institute of Cancer Research.","summary":"The Royal Marsden in London was the world's first hospital dedicated to cancer, opened in 1851, and works as a pair with The Institute of Cancer Research; it ranks seventh in the Newsweek/Statista oncology list. Together they discovered abiraterone and worked out the clinical path for olaparib and PARP inhibition in BRCA-mutated cancers, with Johann de Bono and Andrew Tutt central, and the hospital leads the STAMPEDE prostate platform and breast trials while pioneering MR-linac adaptive radiotherapy. Nuclide links it to the KEYNOTE-048 head and neck paper, to prostate, mesothelioma, sarcoma and neuroendocrine tumour pages, and to bottlenecks about surgery and radiotherapy being under-funded relative to drugs. The question it keeps raising is how to fund trials of treatments no company owns. Stephen Johnston and James Larkin are among the people listed here.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.royalmarsden.nhs.uk"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"London","country":"GB","lat":51.49,"lng":-0.172,"institutionType":"cancer-center","website":"https://www.royalmarsden.nhs.uk","newsweekOncology2026":7,"programs":["Prostate cancer (abiraterone, PARP)","MR-linac","Breast cancer"],"route":"/institutions/royal-marsden/"}
{"id":"sacro-cuore-don-calabria","kind":"institution","name":"IRCCS Sacro Cuore Don Calabria Hospital","aka":["Ospedale Sacro Cuore Don Calabria, Negrar"],"tldr":"Sacro Cuore Don Calabria Hospital in Negrar, near Verona, is a Catholic non-profit hospital recognised as an IRCCS research hospital; it runs medical oncology, radiotherapy, robotic and hepatobiliary surgery and an early-phase trials unit, and OECI accredits it as a Cancer Centre.","summary":"The Sacro Cuore Don Calabria Hospital in Negrar, run by the Opera Don Calabria, is a private non-profit hospital recognised by the Italian Ministry of Health as an IRCCS (scientific research hospital). It has a large oncology department with medical oncology, radiotherapy, oncological surgery including robotic and hepatobiliary surgery, nuclear medicine and an early-phase trials unit, and is accredited by the Organisation of European Cancer Institutes as a Cancer Centre. Its research also covers infectious and tropical diseases, and the hospital collaborates with the University of Verona.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.sacrocuore.it"}],"tags":["oeci-accredited","oeci-cancer-centre","irccs"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Negrar di Valpolicella (Verona)","country":"IT","lat":45.53,"lng":10.938,"institutionType":"hospital","website":"https://www.sacrocuore.it","programs":["Medical oncology and early-phase trials","Robotic and hepatobiliary surgery","Radiotherapy"],"route":"/institutions/sacro-cuore-don-calabria/"}
{"id":"sahlgrenska","kind":"institution","name":"Sahlgrenska University Hospital / Sahlgrenska Center for Cancer Research","aka":["Sahlgrenska","Gothenburg University Hospital"],"tldr":"Western Sweden's university hospital, with a cancer research centre known for melanoma models, radionuclide dosimetry and childhood cancer.","summary":"Sahlgrenska University Hospital is one of the largest hospitals in northern Europe and the cancer centre for the Västra Götaland region. The Sahlgrenska Center for Cancer Research at the University of Gothenburg hosts groups including Jonas Nilsson's on patient-derived melanoma models and immunotherapy, Eva Forssell-Aronsson's on radionuclide therapy dosimetry and Göran Landberg's on breast cancer microenvironment, and the Queen Silvia Children's Hospital is a national paediatric oncology centre. The hospital runs regional radiotherapy, surgical oncology including high-volume colorectal and oesophageal surgery, and haematology with CAR-T, and contributes to Swedish quality registers used in outcomes research.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.sahlgrenska.se/en/"}],"tags":[],"related":[],"indications":["neuroblastoma"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska"],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Gothenburg","country":"SE","lat":57.683,"lng":11.96,"institutionType":"hospital","website":"https://www.sahlgrenska.se/en/","university":"University of Gothenburg","programs":["Melanoma patient-derived models","Radionuclide therapy dosimetry","Paediatric oncology","Surgical oncology","Quality registers"],"route":"/institutions/sahlgrenska/"}
{"id":"sant-orsola-bologna","kind":"institution","name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola","aka":["Sant'Orsola-Malpighi","Policlinico Sant'Orsola","Istituto di Ematologia Seràgnoli"],"tldr":"Bologna's university hospital, home of the Seràgnoli haematology institute and a leading Italian centre for myeloma, lymphoma and CAR-T.","summary":"The Policlinico Sant'Orsola is the university hospital of the world's oldest university and an IRCCS for transplant and oncology. Its Seràgnoli Institute of Haematology, associated with Michele Cavo (myeloma), Pier Luigi Zinzani (lymphoma) and the GIMEMA cooperative group, has run pivotal Italian trials in myeloma transplantation and lymphoma and is one of Italy's principal CAR-T and allogeneic transplant centres. Medical oncology under Andrea Ardizzoni is active in thoracic and gastrointestinal trials, and the hospital has large paediatric oncology, surgical oncology and nuclear medicine departments. The Emilia-Romagna regional network links it with IRST Meldola.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.aosp.bo.it"},{"label":"Haematology","url":"https://www.aosp.bo.it/content/ematologia"}],"tags":[],"related":[],"indications":["dlbcl"],"sections":[],"technologies":[],"targets":["cd20"],"drugs":[],"companies":[],"institutions":["irst-meldola"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Bologna","country":"IT","lat":44.496,"lng":11.36,"institutionType":"hospital","website":"https://www.aosp.bo.it","university":"Università di Bologna","programs":["Seràgnoli haematology institute","Myeloma and lymphoma trials (GIMEMA)","CAR-T and transplantation","Thoracic oncology","Paediatric oncology"],"route":"/institutions/sant-orsola-bologna/"}
{"id":"shandong-cancer-hospital","kind":"institution","name":"Shandong Cancer Hospital and Institute","aka":["Shandong First Medical University Affiliated Cancer Hospital","山东省肿瘤医院"],"tldr":"Shandong Cancer Hospital runs one of China's largest radiotherapy departments under Jinming Yu, with a proton therapy centre and PET-guided adaptive radiotherapy; it has led Chinese trials combining radiotherapy with immunotherapy in lung and oesophageal cancer and studies of brain metastasis management.","summary":"Shandong Cancer Hospital and Institute, founded in 1958 and affiliated to Shandong First Medical University and the Shandong Academy of Medical Sciences, is best known for radiation oncology under Jinming Yu, with one of the largest radiotherapy departments in China, a proton therapy centre and heavy investment in PET-guided and adaptive radiotherapy. It has led Chinese trials combining radiotherapy with immunotherapy in lung and oesophageal cancer and studies of brain metastasis management. The hospital also runs strong thoracic surgery, breast and gynaecological programmes and a provincial cancer registry.","asOf":"2026-09-09","links":[{"label":"Shandong Cancer Hospital","url":"https://www.sdzlyy.org.cn"},{"label":"Shandong First Medical University","url":"https://www.sdfmu.edu.cn"}],"tags":[],"related":[],"indications":["sclc"],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Jinan","country":"CN","lat":36.651,"lng":117.12,"institutionType":"cancer-center","website":"https://www.sdzlyy.org.cn","university":"Shandong First Medical University","programs":["Radiation oncology","Proton therapy","Radio-immunotherapy trials","Thoracic oncology"],"route":"/institutions/shandong-cancer-hospital/"}
{"id":"snmmi","kind":"institution","name":"Society of Nuclear Medicine and Molecular Imaging","aka":["SNMMI","Society of Nuclear Medicine"],"tldr":"The Society of Nuclear Medicine and Molecular Imaging represents US nuclear medicine and publishes the Journal of Nuclear Medicine; its annual meeting is where new PET tracers and radioligand therapy results are presented, and its procedure standards guide PSMA and somatostatin receptor imaging.","summary":"Founded in 1954 as the Society of Nuclear Medicine, SNMMI represents physicians, technologists and scientists in nuclear medicine and molecular imaging and publishes the Journal of Nuclear Medicine and the Journal of Nuclear Medicine Technology. Its annual meeting is where new PET tracers and radioligand therapy results are presented, its procedure standards and appropriate use criteria guide PSMA PET, FDG PET and somatostatin receptor imaging, and its Clinical Trials Network qualifies sites and scanners for multicentre trials. SNMMI runs the Mars Shot fund for radiopharmaceutical research, the Value Initiative on access and reimbursement, and dosimetry and radiation safety education, and it partners with EANM on joint guidelines and the theranostics centres of excellence programme.","asOf":"2026-09-09","links":[{"label":"SNMMI","url":"https://www.snmmi.org"}],"tags":[],"related":["src-snmmi"],"indications":[],"sections":[],"technologies":["pet","pet-ct","psma-pet","fdg-pet","radioligand-therapy","targeted-alpha-therapy","spect"],"targets":[],"drugs":["pluvicto","lutathera","pylarify"],"companies":[],"institutions":["eanm"],"pathways":[],"terms":["theranostics","dosimetry","suv"],"trials":[],"people":["virginia-pappas"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Reston, VA","country":"US","lat":38.958,"lng":-77.357,"institutionType":"consortium","website":"https://www.snmmi.org","programs":["SNMMI Annual Meeting","Journal of Nuclear Medicine","Clinical Trials Network","Appropriate use criteria and procedure standards","Mars Shot Fund"],"route":"/institutions/snmmi/"}
{"id":"tum-munich","kind":"institution","name":"TUM Klinikum rechts der Isar / CCC München","aka":["Klinikum rechts der Isar","Technical University of Munich","Comprehensive Cancer Center Munich (TUM)"],"tldr":"Munich's technical university hospital, one half of the Comprehensive Cancer Center Munich and a leader in PSMA imaging and radiopharmaceutical chemistry.","summary":"The Klinikum rechts der Isar is the university hospital of the Technical University of Munich and, with the LMU, forms the CCC München, a German Cancer Aid Oncology Center of Excellence and DKTK partner site. Its nuclear medicine and radiopharmacy groups developed the radiohybrid PSMA ligands (rhPSMA) that became flotufolastat F-18, and run large theranostic programmes in prostate and neuroendocrine cancer. The TranslaTUM centre houses translational oncology, imaging and immunology, and the hospital has strong pancreatic surgery, haematology and gastrointestinal oncology programmes. Patients access molecular tumour boards and early-phase trials across both Munich university sites.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.mri.tum.de"},{"label":"CCC München","url":"https://www.ccc-muenchen.de"},{"label":"TranslaTUM","url":"https://www.translatum.tum.de"}],"tags":[],"related":["f-18"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["psma-pet","radioligand-therapy","pet-mri","fapi-pet"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":["lmu-munich"],"pathways":[],"terms":["theranostics"],"trials":[],"people":["wolfgang-weber"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Munich","country":"DE","lat":48.137,"lng":11.6,"institutionType":"university","website":"https://www.mri.tum.de","university":"Technische Universität München","programs":["Radiopharmaceutical chemistry and PSMA theranostics","TranslaTUM","Pancreatic surgery","Haematology","CCC München (with LMU)"],"route":"/institutions/tum-munich/"}
{"id":"turku-university-hospital","kind":"institution","name":"Turku University Hospital Cancer Centre","aka":["Tyks","FICAN West"],"tldr":"The university hospital of south-west Finland and host of FICAN West, with OECI Cancer Centre accreditation and a strong PET imaging tradition.","summary":"Turku University Hospital (Tyks) is the tertiary hospital for the Wellbeing Services County of Southwest Finland and the teaching hospital of the University of Turku. Its Cancer Centre hosts the Western Finland Cancer Centre (FICAN West) within the national Finnish Cancer Centre network and is accredited by the Organisation of European Cancer Institutes as a Cancer Centre. Turku is home to the national Turku PET Centre, which supports molecular imaging and radiopharmaceutical research in oncology, and the hospital's research groups are active in prostate cancer, breast cancer and haematological malignancies alongside the University of Turku's Institute of Biomedicine.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.varha.fi"}],"tags":["oeci-accredited","oeci-cancer-centre"],"related":[],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Turku","country":"FI","lat":60.451,"lng":22.267,"institutionType":"hospital","website":"https://www.varha.fi","university":"University of Turku","programs":["FICAN West regional cancer centre","PET imaging (Turku PET Centre)","Prostate and breast cancer research"],"route":"/institutions/turku-university-hospital/"}
{"id":"ucla-jonsson","kind":"institution","name":"UCLA Jonsson Comprehensive Cancer Center","aka":[],"tldr":"Where trastuzumab (Slamon) and palbociclib were developed clinically, and a leader in PSMA PET and melanoma immunotherapy (Ribas).","summary":"The UCLA Jonsson Comprehensive Cancer Center in Los Angeles holds NCI comprehensive designation and is where trastuzumab was developed clinically through Slamon's HER2 work, where palbociclib entered the clinic, and where Antoni Ribas built a leading melanoma immunotherapy programme in checkpoint and TIL research. Johannes Czernin and Jeremie Calais made it a centre for PSMA PET, Hurvitz ran its breast trials programme before moving to Fred Hutch, and Michael A. Teitell, Amar U. Kishan, Aditya Bardia, Denise R. Aberle and the patient Barbara Bradfield are also listed. Nuclide links it to HER2 and PSMA as targets, to trastuzumab, palbociclib and gallium-68 PSMA-11, and to melanoma and prostate cancer. How to extend the HER2 model of target, drug and companion test to new targets remains its recurring theme. Its HER2, melanoma and PSMA programmes are the ones to read.","asOf":"2026-09-04","links":[{"label":"Official website","url":"https://www.uclahealth.org/cancer"}],"tags":[],"related":["ga-68"],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":["her2","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["johannes-czernin","jeremie-calais"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Los Angeles","country":"US","lat":34.066,"lng":-118.446,"institutionType":"cancer-center","website":"https://www.uclahealth.org/cancer","nci":"comprehensive","university":"University of California, Los Angeles","programs":["HER2 (Slamon)","Melanoma immunotherapy (Ribas)","PSMA PET"],"route":"/institutions/ucla-jonsson/"}
{"id":"ucsf","kind":"institution","name":"UCSF Helen Diller Family Comprehensive Cancer Center","aka":[],"tldr":"UCSF is the birthplace of oncogene biology (Bishop, Varmus) and KRAS G12C drugging (Shokat), and a leader in I-SPY adaptive breast trials.","summary":"The UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco is the birthplace of oncogene biology, where Bishop and Varmus made their Nobel-winning discovery, and of KRAS G12C drugging through Shokat's switch-II pocket; it holds NCI comprehensive designation and ranks thirty-third in the Newsweek/Statista oncology list. It leads the I-SPY 2 adaptive platform trial in breast cancer under Laura J. Esserman, runs the UCSF500 panel, and pioneered PSMA PET with Thomas A. Hope, alongside neuro-oncology and prostate programmes. Nuclide links it to KRAS and PSMA, to gallium-68 PSMA-11, to the Ostrem and Shokat paper, and to the MYC and telomere pathways. Whether MYC can be drugged directly, and tolerated, is the open question it is linked to. Alan Ashworth, Eric J. Small and Alan P. Venook are among the people listed.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/UCSF_Helen_Diller_Family_Comprehensive_Cancer_Center","links":[{"label":"Official website","url":"https://cancer.ucsf.edu"}],"tags":[],"related":["ga-68"],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["rahul-aggarwal","thomas-hope","emily-bergsland","katherine-matthay"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"San Francisco","country":"US","lat":37.765,"lng":-122.458,"institutionType":"cancer-center","website":"https://cancer.ucsf.edu","nci":"comprehensive","newsweekOncology2026":33,"university":"University of California, San Francisco","programs":["I-SPY 2 platform trial","KRAS chemistry","PSMA PET","Neuro-oncology"],"route":"/institutions/ucsf/"}
{"id":"uk-duesseldorf","kind":"institution","name":"University Hospital Düsseldorf / CIO Düsseldorf","aka":["Universitätsklinikum Düsseldorf","UKD","Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf"],"tldr":"Düsseldorf's university hospital, a partner in the CIO cancer centre alliance and a leading site for FAPI and PSMA imaging under Frederik Giesel.","summary":"University Hospital Düsseldorf forms, with Aachen, Bonn and Cologne, the Centrum für Integrierte Onkologie (CIO ABCD), a German Cancer Aid Oncology Center of Excellence. Its nuclear medicine department is directed by Frederik Giesel, co-inventor of FAPI PET tracers at Heidelberg, and runs theranostic programmes in prostate and neuroendocrine cancers. The hospital has a large paediatric oncology and haematology department, hepatology and liver cancer programmes, and neurosurgical oncology. Trials from the CIO network give patients access to early-phase immunotherapy and cell therapy studies.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.uniklinik-duesseldorf.de"}],"tags":[],"related":[],"indications":["prostate","neuroendocrine","hcc"],"sections":[],"technologies":["fapi-pet","psma-pet","radioligand-therapy"],"targets":["fap","psma"],"drugs":["fap-2286","pluvicto"],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":["frederik-giesel"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Düsseldorf","country":"DE","lat":51.194,"lng":6.788,"institutionType":"hospital","website":"https://www.uniklinik-duesseldorf.de","university":"Heinrich-Heine-Universität Düsseldorf","programs":["FAPI and PSMA PET","Theranostics","Paediatric oncology","CIO ABCD"],"route":"/institutions/uk-duesseldorf/"}
{"id":"umcg-groningen","kind":"institution","name":"University Medical Center Groningen Comprehensive Cancer Center","aka":["UMCG","UMCG Cancer Center"],"tldr":"The university hospital of the northern Netherlands, home of the country's first proton therapy centre and accredited by OECI as a Comprehensive Cancer Centre.","summary":"The University Medical Center Groningen is the academic hospital of the University of Groningen and the tertiary cancer centre for the northern Netherlands. Its Comprehensive Cancer Center integrates medical oncology, radiotherapy, haematology, surgical oncology, paediatric oncology and molecular imaging, and it opened the first proton therapy centre in the Netherlands in 2018. UMCG is known for molecular imaging with radiolabelled antibodies and drugs (immuno-PET), for lung and breast cancer research, for radiotherapy model-based selection, and for large-scale population research through the Lifelines cohort. It is accredited by the Organisation of European Cancer Institutes as a Comprehensive Cancer Centre.","asOf":"2026-09-10","links":[{"label":"Official website","url":"https://www.umcg.nl"},{"label":"PTCOG: particle therapy facilities in operation","url":"https://www.ptcog.site/index.php/facilities-in-operation-public"}],"tags":["oeci-accredited","oeci-comprehensive-cancer-centre"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Groningen","country":"NL","lat":53.221,"lng":6.575,"institutionType":"hospital","website":"https://www.umcg.nl","university":"University of Groningen","programs":["Proton therapy","Molecular imaging (immuno-PET)","Lung and breast cancer research","Paediatric oncology"],"route":"/institutions/umcg-groningen/"}
{"id":"uppsala-akademiska","kind":"institution","name":"Uppsala University Hospital / Uppsala University","aka":["Akademiska sjukhuset","Skandion Clinic","Rudbeck Laboratory"],"tldr":"Uppsala University Hospital is Sweden's oldest; its neuroendocrine tumour centre built by Kjell Öberg is an ENETS Centre of Excellence with long experience of somatostatin analogues and radionuclide therapy, and Sweden's national Skandion proton clinic opened next door in 2015.","summary":"Akademiska sjukhuset and Uppsala University form one of Scandinavia's leading cancer research environments. Uppsala's neuroendocrine tumour centre, built by Kjell Öberg, is an ENETS Centre of Excellence with long experience of somatostatin analogues and peptide receptor radionuclide therapy, and Bengt Glimelius's group shaped Nordic rectal cancer radiotherapy trials. The Skandion Clinic, Sweden's national proton therapy facility co-owned by the university regions, opened in Uppsala in 2015 using IBA equipment. Tobias Sjöblom's laboratory contributed to the first colorectal cancer exome sequencing and runs the U-CAN biobank, Uppsala scientists founded Olink Proteomics, and the Uppsala Clinical Research Center supports national trials.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.akademiska.se"},{"label":"Skandion Clinic","url":"https://www.skandionkliniken.se"}],"tags":[],"related":[],"indications":["neuroendocrine","prostate","glioblastoma"],"sections":[],"technologies":["radioligand-therapy"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["iba"],"institutions":["karolinska"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Uppsala","country":"SE","lat":59.849,"lng":17.637,"institutionType":"hospital","website":"https://www.akademiska.se","university":"Uppsala University","programs":["Neuroendocrine tumour centre","Skandion proton clinic","Gastrointestinal radiotherapy trials","U-CAN biobank","Proteomics"],"route":"/institutions/uppsala-akademiska/"}
{"id":"usb-basel","kind":"institution","name":"University Hospital Basel / Tumour Centre","aka":["USB","Universitätsspital Basel","Tumorzentrum Basel"],"tldr":"University Hospital Basel coordinates cancer care in the home city of Roche and Novartis; its groups run early-phase tumour immunology trials, study breast cancer metastasis, and develop peptide radioligands such as exendin-based imaging of insulinomas.","summary":"The Tumour Centre of University Hospital Basel coordinates cancer care in a city that is also headquarters to Roche and Novartis and home to the Friedrich Miescher Institute and the University of Basel's Department of Biomedicine. Alfred Zippelius and Heinz Läubli lead tumour immunology and early-phase immunotherapy trials, Mohamed Bentires-Alj studies breast cancer metastasis, Viola Heinzelmann-Schwarz heads gynaecological oncology, and the nuclear medicine and radiopharmaceutical chemistry groups (Damian Wild, Melpomeni Fani) develop novel peptide radioligands, including exendin-based imaging of insulinomas. The hospital runs haematology and CAR-T, thoracic and visceral surgery, and radiotherapy, and hosts SAKK and pharma-sponsored trials.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.unispital-basel.ch/en/"},{"label":"Tumorzentrum","url":"https://www.unispital-basel.ch/en/tumorzentrum"}],"tags":[],"related":[],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":[],"drugs":[],"companies":["novartis"],"institutions":["inselspital-bern","usz-zurich"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Basel","country":"CH","lat":47.561,"lng":7.582,"institutionType":"hospital","website":"https://www.unispital-basel.ch/en/","university":"Universität Basel","programs":["Tumour immunology and early-phase immunotherapy","Radiopharmaceutical chemistry","Breast cancer metastasis research","Gynaecological oncology","Haematology and CAR-T"],"route":"/institutions/usb-basel/"}
{"id":"usz-zurich","kind":"institution","name":"University Hospital Zurich / Comprehensive Cancer Center Zurich","aka":["USZ","CCCZ","UniversitätsSpital Zürich"],"tldr":"Zurich's university hospital and cancer centre, a world reference in neuro-oncology, melanoma and single-cell tumour imaging.","summary":"The Comprehensive Cancer Center Zurich brings together the University Hospital Zurich, the University of Zurich and ETH Zurich. Michael Weller's neurology department chairs the EORTC Brain Tumor Group and shapes glioma guidelines, and Zurich was a leading site in the glioblastoma trials that introduced temozolomide and tumour-treating fields. Reinhard Dummer's dermatology clinic is one of Europe's foremost melanoma centres and led oncolytic virus and targeted therapy studies, Bernd Bodenmiller's laboratory developed imaging mass cytometry for spatial single-cell tumour analysis, and the haematology and nuclear medicine departments run CAR-T and theranostics programmes. The centre is OECI-accredited and hosts a large early-phase unit.","asOf":"2026-09-09","links":[{"label":"Homepage","url":"https://www.usz.ch/en/"},{"label":"Comprehensive Cancer Center Zurich","url":"https://www.cccz.ch"}],"tags":[],"related":[],"indications":["glioblastoma","dlbcl"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Zurich","country":"CH","lat":47.376,"lng":8.551,"institutionType":"hospital","website":"https://www.usz.ch/en/","university":"University of Zurich","programs":["Neuro-oncology (EORTC Brain Tumor Group)","Melanoma and dermato-oncology","Imaging mass cytometry","CAR-T and haematology","Theranostics"],"route":"/institutions/usz-zurich/"}
{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","aka":["KEGG hsa05231","Choline metabolism in cancer"],"tldr":"This KEGG map shows how cancer cells rewire the handling of choline, a nutrient used to build cell membranes, so that growth signals and membrane building feed each other. It matters because the resulting build-up of phosphocholine is visible on MR spectroscopy and PET scans and is one of the metabolic hallmarks of cancer.","summary":"Abnormal choline metabolism is a metabolic hallmark associated with oncogenesis and tumour progression. KEGG map hsa05231 draws how oncogenic signalling through RAS-ERK and PI3K-AKT, together with transcription factors such as hypoxia-inducible factor 1 (HIF1), raises the expression and activity of choline cycle enzymes. Choline enters through transporters (CHT1, CTL1, OCT2), is phosphorylated by choline kinase alpha (CHKA) to phosphocholine, and is built into phosphatidylcholine by the Kennedy pathway. Phospholipases C and D and the phosphatidylcholine-specific enzymes then break membrane phosphatidylcholine back down to phosphocholine, diacylglycerol (DAG) and phosphatidic acid. These products act as second messengers: DAG activates protein kinase C and phosphatidic acid supports the RAS-RAF1-MAPK cascade and mTOR, so membrane turnover and growth signalling reinforce each other.\n\nGlunde, Bhujwalla and Ronen, Nature Reviews Cancer, 2011 (doi:10.1038/nrc3162) review the field: the increase in total choline-containing compounds, and in particular the shift from glycerophosphocholine to phosphocholine, is seen across breast, prostate, brain and other cancers, is driven by CHKA over-expression and increased transporter activity, and can be imaged non-invasively by magnetic resonance spectroscopy and by choline PET. Response to targeted drugs (for example PI3K or MAPK inhibitors) lowers phosphocholine, making it a pharmacodynamic marker.\n\nWhat can be done: choline kinase inhibitors have been developed and one (TCD-717) reached a phase 1 trial, but none is approved. Today the choline pathway is used as a read-out rather than a target: choline imaging helps diagnose and monitor tumours, and drugs against the upstream drivers (PI3K/AKT/mTOR inhibitors such as alpelisib, capivasertib and everolimus; MEK inhibitors such as trametinib) lower choline metabolite levels as they work.","asOf":"2026-09-10","links":[{"label":"KEGG map hsa05231","url":"https://www.kegg.jp/pathway/hsa05231"},{"label":"Review: Choline metabolism in malignant transformation","url":"https://doi.org/10.1038/nrc3162"}],"tags":[],"related":["hif-vhl"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"A building site where the bricks (choline) are also the walkie-talkies. The cell orders far more bricks than it needs for walls, keeps knocking finished walls down and rebuilding them, and every knocked-down brick sends a message telling the foreman to build faster. The pile of loose bricks is what the scanner sees.","nodes":[{"id":"rtk","label":"Growth factor receptors (EGFR, HER2)","x":50,"y":5},{"id":"ras","label":"RAS / RAF / MAPK","x":25,"y":22},{"id":"pi3k","label":"PI3K / AKT / mTOR","x":75,"y":22},{"id":"hif","label":"HIF1","x":90,"y":42},{"id":"transport","label":"Choline transporters (CHT1, CTL1)","x":10,"y":45},{"id":"chka","label":"Choline kinase alpha (CHKA)","x":40,"y":45},{"id":"pcho","label":"Phosphocholine (PCho)","x":40,"y":65},{"id":"ptdcho","label":"Phosphatidylcholine (membrane)","x":70,"y":65},{"id":"plc","label":"PLC / PLD","x":90,"y":80},{"id":"dag","label":"DAG / phosphatidic acid","x":55,"y":85},{"id":"pkc","label":"Protein kinase C","x":25,"y":85},{"id":"out","label":"Proliferation, survival","x":50,"y":98}],"edges":[{"from":"rtk","to":"ras","type":"activates"},{"from":"rtk","to":"pi3k","type":"activates"},{"from":"ras","to":"chka","type":"activates"},{"from":"pi3k","to":"chka","type":"activates"},{"from":"pi3k","to":"hif","type":"activates"},{"from":"hif","to":"chka","type":"activates"},{"from":"hif","to":"transport","type":"activates"},{"from":"transport","to":"chka","type":"activates"},{"from":"chka","to":"pcho","type":"activates"},{"from":"pcho","to":"ptdcho","type":"activates"},{"from":"plc","to":"ptdcho","type":"inhibits"},{"from":"plc","to":"dag","type":"activates"},{"from":"dag","to":"pkc","type":"activates"},{"from":"dag","to":"ras","type":"activates"},{"from":"pkc","to":"out","type":"activates"},{"from":"pcho","to":"out","type":"activates"}],"interventions":["Choline imaging (MR spectroscopy, choline PET) to diagnose tumours and read out response to therapy","Cut the upstream drivers: PI3K/AKT/mTOR inhibitors (alpelisib, capivasertib, everolimus) and MEK inhibitors (trametinib) lower phosphocholine as they act","Choline kinase alpha inhibitors (TCD-717 reached phase 1), no approved agent","HIF2 inhibition (belzutifan) where hypoxia signalling drives metabolic rewiring, approved in VHL-related and renal cancers"],"route":"/pathways/choline-metabolism-in-cancer/"}
{"id":"hif-vhl","kind":"pathway","name":"VHL / HIF oxygen sensing","aka":[],"tldr":"The VHL/HIF pathway is how cells sense oxygen (the 2019 Nobel Prize). VHL destroys HIF when oxygen is present. Kidney cancers lose VHL, so HIF-2α is permanently on and drives blood vessel growth and proliferation.","summary":"In normoxia, prolyl hydroxylases (PHD) hydroxylate HIF-α, allowing the VHL E3 ligase to ubiquitinate it for proteasomal degradation. In hypoxia (or with VHL loss in ~90% of clear-cell RCC), HIF-α accumulates, dimerises with HIF-1β (ARNT), and transcribes VEGF, PDGF, GLUT1, CAIX, cyclin D1, and EPO. HIF-2α is the oncogenic paralogue in RCC; belzutifan blocks its dimerisation. CAIX is a PET and radioligand target (89Zr-girentuximab).","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Hypoxia-inducible_factor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Hypoxia-inducible_factor"}],"tags":[],"related":["zr-89"],"indications":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"VHL is the shredder that destroys the 'we are suffocating' memo whenever there is oxygen around. Kidney cancer breaks the shredder, so the memo piles up and the cell keeps ordering new blood vessels and sugar.","nodes":[{"id":"o2","label":"Oxygen","x":20,"y":8},{"id":"phd","label":"PHD hydroxylases","x":20,"y":28},{"id":"vhl","label":"VHL E3 ligase","x":20,"y":48},{"id":"hif","label":"HIF-2α","x":55,"y":48},{"id":"arnt","label":"HIF-1β (ARNT)","x":85,"y":35},{"id":"genes","label":"VEGF, CAIX, GLUT1, cyclin D1","x":55,"y":72},{"id":"out","label":"Angiogenesis, glycolysis, growth","x":55,"y":92}],"edges":[{"from":"o2","to":"phd","type":"activates"},{"from":"phd","to":"vhl","type":"activates"},{"from":"vhl","to":"hif","type":"inhibits"},{"from":"arnt","to":"hif","type":"activates"},{"from":"hif","to":"genes","type":"activates"},{"from":"genes","to":"out","type":"activates"}],"interventions":["Belzutifan (HIF-2α) in VHL disease and RCC, adjuvant with pembrolizumab (2026)","VEGF-directed therapy downstream","CAIX-targeted imaging (89Zr-girentuximab) and radioligands in development"],"route":"/pathways/hif-vhl/"}
{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","aka":[],"tldr":"Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.","summary":"Lineage plasticity requires loss of the gatekeepers TP53 and RB1 (Ku et al., Mu et al. 2017), which unlocks SOX2, EZH2-mediated repression of lineage genes, and reactivation of neural programmes (ASCL1, NEUROD1, INSM1, BRN2), producing AR-indifferent neuroendocrine prostate cancer in 15-20% of castration-resistant cases after potent AR inhibitors, and small-cell transformation in ~5-15% of EGFR-mutant NSCLC on osimertinib (also after ALK inhibitors and in immunotherapy-treated adenocarcinoma). Related transitions: squamous transdifferentiation of adenocarcinoma, sarcomatoid dedifferentiation in RCC and mesothelioma, MITF-low neural-crest states in melanoma under BRAF inhibitors, and blast/Richter transformation in lymphoid cancers. The new state expresses DLL3, SEZ6, B7-H3, CEACAM5 and loses PSMA or EGFR dependence, is transiently sensitive to platinum-etoposide, and is detected by biopsy at progression (recommended when PSA is low relative to disease burden or ctDNA shows TP53/RB1 loss) and by DLL3 PET. Therapeutics: DLL3 engagers (tarlatamab), EZH2 inhibitors (mevrometostat + enzalutamide, tazemetostat) to block or reverse the switch, Aurora A inhibitors for MYCN/ASCL1 states, and B7-H3 or SEZ6 ADCs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"Ku et al., Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance (Science 2017)","url":"https://doi.org/10.1126/science.aah4199"},{"label":"Beltran et al., Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer (Nat Med 2016)","url":"https://doi.org/10.1038/nm.4045"}],"tags":["mechanism","mechanics-atlas"],"related":[],"indications":["prostate","sclc"],"sections":[],"technologies":[],"targets":["dll3","b7h3","ceacam5","psma"],"drugs":["enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"A shop that sells hats is fined every time it sells a hat (AR blockade). One day it reopens as a bakery. The fine no longer applies, the old inspectors (PSA, PSMA scans) see nothing, and only a new set of tools works against the new business.","nodes":[{"id":"adeno","label":"Adenocarcinoma (AR / EGFR)","x":12,"y":15},{"id":"drug","label":"ARPI or EGFR TKI pressure","x":12,"y":48},{"id":"loss","label":"TP53 + RB1 loss","x":45,"y":15},{"id":"sox2","label":"SOX2, EZH2, ASCL1/NEUROD1","x":45,"y":48},{"id":"ne","label":"Neuroendocrine / small-cell","x":78,"y":30},{"id":"dll3","label":"DLL3, B7-H3, SEZ6 surface","x":78,"y":62,"targetId":"dll3"},{"id":"indiff","label":"AR / EGFR indifferent","x":45,"y":82},{"id":"tx","label":"Tarlatamab, platinum-etoposide","x":78,"y":92},{"id":"ezh2i","label":"EZH2 inhibitors block switch","x":12,"y":82}],"edges":[{"from":"adeno","to":"ne","type":"activates"},{"from":"drug","to":"sox2","type":"activates"},{"from":"loss","to":"sox2","type":"activates"},{"from":"sox2","to":"ne","type":"activates"},{"from":"ne","to":"dll3","type":"activates"},{"from":"ne","to":"indiff","type":"activates"},{"from":"drug","to":"adeno","type":"inhibits"},{"from":"tx","to":"ne","type":"inhibits"},{"from":"ezh2i","to":"sox2","type":"inhibits"}],"interventions":["Re-biopsy at progression when the clinical picture and markers diverge; ctDNA TP53/RB1 loss as a warning","DLL3 T-cell engager tarlatamab (SCLC; trials in neuroendocrine prostate cancer); B7-H3 and SEZ6 ADCs","EZH2 inhibitors (mevrometostat with enzalutamide, tazemetostat) to prevent or reverse plasticity; Aurora A inhibitors for MYCN/ASCL1-high states","Platinum-etoposide gives transient responses in transformed disease"],"route":"/pathways/lineage-plasticity-neuroendocrine/"}
{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","aka":["KEGG hsa05215","Prostate cancer"],"tldr":"KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.","summary":"The KEGG prostate cancer map (hsa05215) draws the androgen receptor (AR) as the central node. Testosterone is converted by SRD5A2 to dihydrotestosterone, which releases AR from HSP90 chaperones so it enters the nucleus and, with co-activators (CREBBP, EP300, NCOA family), switches on target genes such as KLK3 (PSA), TMPRSS2 and, through the TMPRSS2-ERG fusion, the ERG oncogene. During androgen deprivation the map shows how AR signalling is re-established: AR gene amplification, AR mutations that respond to other ligands, altered co-activator activity and growth-factor cross-talk. The second arm is growth-factor signalling: EGFR, ERBB2, IGF1R, FGFR and PDGFR feed PI3K to AKT to mTOR, and AKT both stabilises AR output and inhibits FOXO and BAD. PTEN loss, which is very common, and NKX3.1 loss lower p27 (CDKN1B) and remove restraint on the cell cycle, while MDM2 activation by AKT lowers p53. KEGG also draws GSTP1 silencing, which removes carcinogen detoxification in prostatic intraepithelial neoplasia, and FOLH1 (PSMA), the surface protein now used for imaging and radioligand therapy. Watson, Arora and Sawyers, Nat Rev Cancer, 2015 (doi:10.1038/nrc4016) review how castration-resistant tumours restore AR signalling through amplification, ligand-binding-domain mutations (such as F877L under enzalutamide), constitutively active splice variants like AR-V7, intratumoural androgen synthesis and glucocorticoid receptor substitution, and how PTEN loss and lineage plasticity provide AR-independent escape.\n\nWhat drugs do about it: androgen deprivation (GnRH agonists or antagonists) removes the ligand; abiraterone blocks CYP17-dependent androgen synthesis; the AR antagonists enzalutamide, apalutamide and darolutamide stop AR binding DNA even when amplified; the AKT inhibitor capivasertib with abiraterone is approved for PTEN-deficient metastatic castration-resistant disease; and the PSMA radioligand lutetium-177 vipivotide tetraxetan (Pluvicto) delivers radiation to FOLH1-expressing cells after AR pathway inhibitors.","asOf":"2026-09-10","links":[{"label":"KEGG map hsa05215","url":"https://www.kegg.jp/pathway/hsa05215"},{"label":"Review: Emerging mechanisms of resistance to AR inhibitors in prostate cancer","url":"https://doi.org/10.1038/nrc4016"}],"tags":[],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":["enzalutamide","abiraterone","pluvicto","olaparib"],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"The androgen receptor is an engine that runs on testosterone. Cutting the fuel (androgen deprivation) works until the tumour fits a bigger tank (AR amplification) or an engine that runs on anything (AR mutations and splice variants). Enzalutamide and its cousins clamp the engine itself; capivasertib deals with the separate PI3K/AKT motor that PTEN loss switches on.","nodes":[{"id":"androgen","label":"Testosterone to DHT (SRD5A2)","x":20,"y":6},{"id":"ar","label":"Androgen receptor (amplified, mutated)","x":20,"y":30},{"id":"coact","label":"Co-activators (CBP/p300, NCOA)","x":50,"y":20},{"id":"argenes","label":"KLK3 (PSA), TMPRSS2-ERG","x":20,"y":56},{"id":"rtk","label":"EGFR, IGF1R, FGFR, PDGFR","x":80,"y":6},{"id":"pten","label":"PTEN, NKX3.1 (lost)","x":95,"y":30},{"id":"pi3k","label":"PI3K / AKT / mTOR","x":75,"y":40},{"id":"p27","label":"p27 (CDKN1B)","x":75,"y":62},{"id":"mdm2","label":"MDM2 to p53","x":95,"y":62},{"id":"psma","label":"FOLH1 (PSMA)","x":50,"y":78,"targetId":"psma"},{"id":"out","label":"Growth, survival, castration resistance","x":50,"y":95}],"edges":[{"from":"androgen","to":"ar","type":"activates"},{"from":"coact","to":"ar","type":"activates"},{"from":"ar","to":"argenes","type":"activates"},{"from":"argenes","to":"out","type":"activates"},{"from":"rtk","to":"pi3k","type":"activates"},{"from":"pten","to":"pi3k","type":"inhibits"},{"from":"pi3k","to":"ar","type":"activates"},{"from":"pi3k","to":"p27","type":"inhibits"},{"from":"pi3k","to":"mdm2","type":"activates"},{"from":"p27","to":"out","type":"inhibits"},{"from":"mdm2","to":"out","type":"activates"},{"from":"psma","to":"out","type":"activates"}],"interventions":["Androgen deprivation (GnRH agonists or antagonists) combined with an AR pathway inhibitor: enzalutamide, apalutamide, darolutamide or abiraterone (CYP17 inhibitor)","AKT inhibitor capivasertib plus abiraterone for PTEN-deficient metastatic castration-resistant prostate cancer","PSMA radioligand therapy (lutetium-177 vipivotide tetraxetan, Pluvicto) for PSMA-positive disease after AR pathway inhibitors","PARP inhibitors (olaparib, niraparib, talazoparib) with an AR pathway inhibitor for BRCA-altered disease","Docetaxel or cabazitaxel chemotherapy; radiotherapy or prostatectomy for localised disease"],"route":"/pathways/prostate-cancer-signalling/"}
{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","aka":[],"tldr":"Beta particles (lutetium-177) travel millimetres and are good for bulky disease; alpha particles (actinium-225) travel a few cells' width and kill with far higher energy.","summary":"This is about alpha particles versus beta particles in radioligand therapy, not the alpha/beta ratio of the linear-quadratic model used in external-beam fractionation. Beta and alpha emitters are the two kinds of particle used in radioligand therapy. Beta particles from lutetium-177 have low linear energy transfer and a range of 1 to 10 mm, so their crossfire helps in heterogeneous bulky tumours at the cost of marrow toxicity. Alpha particles from actinium-225 have very high linear energy transfer, around 100 keV per micrometre, travel only 50 to 100 micrometres and cause oxygen-independent DNA breaks, though daughter recoil redistributes dose and actinium-225 supply is the bottleneck. The distinction underlies the Radioligand therapy (beta emitters) and Targeted alpha therapy technologies and the pairing Beta radioligand to alpha radioligand, and it is referenced by Radium-223 dichloride and the Neuroendocrine tumours entry.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy"}],"tags":[],"related":["lu-177","ac-225","ra-223"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/alpha-vs-beta/"}
{"id":"anaemia","kind":"term","name":"Anaemia","aka":["anemia","anaemic","anemic","low haemoglobin","low hemoglobin","haemoglobin","hemoglobin","transfusion-dependent","transfusion dependence","transfusion independence","red cell transfusion","erythropoiesis-stimulating agent","ESA","ESAs","iron deficiency","erythropoiesis-stimulating agents"],"tldr":"A shortage of red blood cells or haemoglobin, causing tiredness and breathlessness. In cancer it comes from the disease itself (marrow infiltration, bleeding, inflammation), from chemotherapy suppressing the marrow, and from some targeted drugs.","summary":"Present in 30-90% of patients depending on cancer and treatment; a defining feature of myeloma, MDS and leukaemia, and the dose-limiting toxicity of PARP inhibitors (olaparib, talazoparib) and of some ADCs and radioligands. Managed by treating the cause, iron replacement, red cell transfusion (with restrictive thresholds) and, cautiously, erythropoiesis-stimulating agents, which raise thrombosis risk and were linked to worse outcomes when used to high targets. Transfusion independence is an endpoint in MDS trials (luspatercept, imetelstat). Fatigue from anaemia is one of the most common and under-treated symptoms in oncology.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Anemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Anemia"}],"tags":[],"related":["cytopenias","thrombocytopenia"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","route":"/terms/anaemia/"}
{"id":"antigen","kind":"term","name":"Antigen","aka":["antigens","tumour antigen","tumour antigens","tumor antigen","tumor antigens","target antigen","target antigens","antigenic","tumour-associated antigen","tumour-associated antigens","tumor-associated antigen","tumor-associated antigens","antigen-negative","antigen loss"],"tldr":"Anything an antibody or immune cell can recognise, typically a protein on a cell's surface. In cancer, an antigen is the flag that tells a drug or an immune cell 'this is the cell to attack'.","summary":"Most cancer antigens are ordinary human proteins that a tumour makes in unusual amounts (HER2, TROP2, CD19, PSMA), so drugs targeting them also touch normal cells that carry a little; truly tumour-specific antigens arise from mutations (neoantigens) or from viral proteins. A good drug antigen is abundant on tumour cells, scarce on essential normal tissue, and stable over time. Tumours escape by losing the antigen, which is how CD19-negative relapse defeats CAR-T, and by hiding the pieces of antigen they would normally display to T cells.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antigen"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":["her2","trop2","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics","route":"/terms/antigen/"}
{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","aka":["ARPI","ARPIs","ARSI","androgen receptor signalling inhibitor","androgen receptor pathway inhibitor","novel hormonal agent","NHA","next-generation antiandrogen","second-generation antiandrogen","AR antagonist","AR inhibitor","antiandrogen","anti-androgen","AR-V7","AR-targeted","AR antagonists"],"tldr":"The newer prostate cancer hormone pills (abiraterone, enzalutamide, apalutamide, darolutamide) that block the androgen receptor or the last steps of androgen production, used on top of standard testosterone suppression.","summary":"Abiraterone blocks CYP17 androgen synthesis (given with prednisone); enzalutamide, apalutamide and darolutamide are potent AR antagonists. Adding an ARPI to ADT extends survival in metastatic hormone-sensitive disease (LATITUDE, ARCHES, TITAN, ARASENS), in non-metastatic castration-resistant disease and in castration-resistant disease before or after docetaxel. Resistance arises via AR amplification, ligand-binding domain mutations, the AR-V7 splice variant and lineage plasticity to neuroendocrine disease; switching ARPIs after failure gives little benefit, so PSMA radioligands, PARP inhibitors and chemotherapy follow. Older antiandrogens (bicalutamide) are weaker first-generation drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antiandrogen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antiandrogen"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/arpi/"}
{"id":"biochemical-recurrence","kind":"term","name":"Biochemical recurrence (BCR)","aka":[],"tldr":"PSA rising again after surgery or radiation, usually years before anything shows on a scan.","summary":"Biochemical recurrence is a rising PSA after treatment for prostate cancer, usually years before anything is visible on a scan. It is defined as a PSA of 0.2 ng/mL or more after prostatectomy, or a rise of 2 ng/mL above the nadir after radiation. PSMA PET, with agents such as fluciclovine F-18 and Illuccix, can now find the recurrent disease at very low PSA levels in most men, opening the way to salvage radiation or metastasis-directed therapy. The EMBARK trial, reported in 2023, showed that enzalutamide with or without androgen deprivation delays metastasis in high-risk recurrence defined by a short PSA doubling time. The term is linked from the PSA entry and from ideas on PSMA-PET-guided metastasis-directed therapy and on localising residual disease.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Biochemical_recurrence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biochemical_recurrence"}],"tags":[],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["embark"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","route":"/terms/biochemical-recurrence/"}
{"id":"bone-marrow","kind":"term","name":"Bone marrow","aka":["marrow","bone-marrow","marrow suppression","myelosuppression","myelosuppressive","blood counts","blood count","low blood counts","neutropenia","neutropenic","anaemia","anemia","thrombocytopenia"],"tldr":"The soft tissue inside bones where all blood cells are made. Chemotherapy damages it, causing the low blood counts that limit how much treatment a patient can take.","summary":"Blood stem cells in the marrow produce billions of red cells, white cells and platelets each day; because they divide constantly, they are collateral damage for most chemotherapy and for some ADC payloads, radiotherapy to bone and radioligands. The consequences are anaemia (fatigue), neutropenia (infection risk, sometimes life-threatening) and thrombocytopenia (bleeding), which together are the commonest reason for dose delays and reductions. Growth factors such as G-CSF speed recovery of white cells, and a marrow biopsy is how leukaemias and myeloma are diagnosed and monitored.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_marrow","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_marrow"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics","route":"/terms/bone-marrow/"}
{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","aka":["bone metastasis","skeletal metastases","skeletal-related events","skeletal-related event","SRE","bone-only","bone-predominant","osseous metastases","pathological fracture","spinal cord compression"],"tldr":"Cancer spread to the bones, most common in prostate, breast, lung, kidney and thyroid cancer and myeloma. It causes pain, fractures and high calcium, and the complications are counted in trials as 'skeletal-related events'.","summary":"Skeletal-related events (fracture, need for radiotherapy or surgery to bone, spinal cord compression, hypercalcaemia) are reduced 30-40% by bone-modifying agents (zoledronic acid, denosumab). Single-fraction 8 Gy radiotherapy relieves pain as well as longer courses; SBRT gives more durable relief for spine metastases. Bone-seeking radiopharmaceuticals (radium-223, strontium-89) treat bone-predominant prostate cancer, and bone-only disease has a better prognosis than visceral spread in breast cancer. Spinal cord compression is an emergency needing steroids and urgent radiotherapy or surgery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_metastasis"}],"tags":[],"related":["ra-223","sr-89"],"indications":["prostate","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["radium-223"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy","route":"/terms/bone-metastases/"}
{"id":"complete-response-term","kind":"term","name":"Complete response (CR) and partial response (PR)","aka":["complete response","complete responses","complete remission","complete remissions","CR rate","CRi","CR/CRi","complete response rate","stringent complete response","sCR","partial response","partial responses","partial remission","PR rate","very good partial response","VGPR","stable disease","best response","best overall response","deep response","deep responses","complete response rates"],"tldr":"A complete response means every measurable trace of the cancer has disappeared on scans or in the marrow; a partial response means it has shrunk by at least 30% (RECIST) but is still there. Neither is the same as cure: microscopic disease can remain.","summary":"Solid tumour responses are defined by RECIST 1.1 (complete: all target lesions gone and nodes <10 mm; partial: ≥30% decrease in summed diameters; progressive: ≥20% increase or new lesions; stable: neither); lymphoma uses Lugano and PET; leukaemia uses marrow blast count and count recovery (CR, CRi for incomplete recovery); myeloma uses IMWG (stringent CR, VGPR, PR). Complete responses are the strongest single-arm signal and, when durable, drive accelerated approvals; the proportion of complete responders and the depth of response (MRD, ctDNA clearance) increasingly predict long-term outcome. In neoadjuvant settings pathological complete response is judged on the resected specimen, and clinical complete response guides organ preservation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","route":"/terms/complete-response-term/"}
{"id":"crossover","kind":"term","name":"Crossover in trials","aka":["cross-over","crossover-adjusted","crossover adjustment","adjusted for crossover","permitted crossover","crossover was permitted","crossover rate","post-progression therapy","subsequent therapy","subsequent treatment","RPSFT","rank-preserving structural failure time","IPCW","treatment switching","unplanned crossover","confounded by crossover"],"tldr":"When patients in a trial's control arm are allowed to switch to the experimental drug after their cancer progresses. It is fair to patients but blurs the survival comparison, because the control group has now had the drug too.","summary":"Crossover is common in trials of drugs already approved elsewhere or clearly active (imatinib in GIST, osimertinib in FLAURA, 177Lu-PSMA in VISION and PSMAfore, where 84% of controls crossed over) and explains why such trials often show large progression-free survival gains but little or no overall survival difference. Statistical corrections (rank-preserving structural failure time, inverse probability of censoring weighting) estimate what survival would have been without crossover but rely on assumptions and are treated cautiously by regulators, who may still demand an OS trend. In regulatory debates, crossover cuts both ways: it can hide a true survival benefit or excuse its absence.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Crossover_study","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Crossover_study"}],"tags":[],"related":["estimand","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","route":"/terms/crossover/"}
{"id":"curie-siopen-score","kind":"term","name":"MIBG Curie and SIOPEN scores","aka":["Curie score","SIOPEN score","MIBG score","MIBG avidity","MIBG-avid","MIBG-non-avid","semi-quantitative MIBG scoring","123I-MIBG scan","MIBG scintigraphy","18F-MFBG PET","MFBG PET"],"tldr":"Neuroblastoma soaks up MIBG, a radioactive cousin of noradrenaline; the Curie and SIOPEN scores count how many body regions still light up on the scan, and a score that has not fallen enough after the first rounds of chemotherapy marks a child who is unlikely to be cured with the standard plan.","summary":"What is measured: the extent of MIBG-avid disease on a whole-body scan. How: iodine-123 MIBG planar and SPECT imaging (with a bone scan or FDG PET for the roughly 10 percent of tumours that do not take up MIBG); the Curie score grades nine skeletal segments and one soft-tissue site from 0 to 3 (maximum 30) and the SIOPEN score grades twelve skeletal segments from 0 to 6 (maximum 72). What a result changes: at diagnosis it stages metastatic disease and establishes MIBG avidity for later iodine-131 MIBG therapy; after induction, a Curie score above 2 (COG A3973) or a SIOPEN score above 3 predicts worse event-free survival in high-risk disease and is used to stratify and to select patients for intensified or experimental arms, such as adding iodine-131 MIBG in COG ANBL1531; the International Neuroblastoma Response Criteria of 2017 use MIBG to score skeletal response. Fluorine-18 MFBG PET, a same-day tracer with higher resolution, is replacing MIBG in trials. Where it matters: neuroblastoma and high-risk neuroblastoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["mibg-theranostics","i131-mibg","fdg-pet","f-18","i-123","i-131"],"indications":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","route":"/terms/curie-siopen-score/"}
{"id":"cytopenias","kind":"term","name":"Cytopenias and myelosuppression","aka":["cytopenia","cytopenias","myelosuppression","myelosuppressive","bone marrow suppression","marrow suppression","marrow toxicity","haematological toxicity","hematological toxicity","haematologic toxicity","hematologic toxicity","pancytopenia","bicytopenia","lymphopenia","lymphocytopenia","prolonged cytopenias","late cytopenias","ICAHT","immune effector cell-associated haematotoxicity","count recovery","blood counts","full blood count","complete blood count","CBC"],"tldr":"The umbrella term for low blood counts of any kind (white cells, red cells, platelets) when treatment suppresses the bone marrow. Most chemotherapy causes it temporarily; radioligands, CAR-T and some pills cause longer-lasting versions.","summary":"Myelosuppression is the shared toxicity of cytotoxic chemotherapy, conditioning regimens, lymphodepletion, radioligand therapy (177Lu-PSMA, PRRT) and a range of targeted agents, graded per lineage by CTCAE; pancytopenia means all three lineages are low. Blood counts before each cycle gate treatment, and delays and dose reductions are the standard responses. After CAR-T, prolonged and biphasic cytopenias (ICAHT) affect a third of patients and drive infection deaths months after infusion; lymphopenia is a marker of poorer immunotherapy outcomes. Therapy-related MDS is the late, permanent form of marrow injury.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Myelosuppression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myelosuppression"}],"tags":[],"related":["thrombocytopenia","anaemia","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","route":"/terms/cytopenias/"}
{"id":"dosimetry","kind":"term","name":"Dosimetry","aka":[],"tldr":"Measuring how much radiation dose each organ and tumour actually received from a radioactive drug.","summary":"Dosimetry is the measurement of how much radiation dose each organ and each tumour actually received from a radioactive drug. It relies on post-therapy SPECT/CT imaging at several time points and enables personalised activity prescription instead of fixed doses, and regulators and payers increasingly require it. The term is linked to the SPECT & bone scan and Radioligand therapy (beta emitters) technologies and to Radioembolisation (TARE / SIRT, yttrium-90), Auger-electron therapy and Total-body PET for screening. It is referenced by the Hepatocellular carcinoma and Neuroendocrine tumours entries, the radiopharmaceutical roadmap and the bottleneck on wrong doses, and by ideas on dosimetry-personalised PRRT instead of four fixed cycles and total-body PET for personalised radioligand dosing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Dosimetry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":[],"related":["y-90"],"indications":[],"sections":[],"technologies":["spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/dosimetry/"}
{"id":"estimand","kind":"term","name":"Estimands and intercurrent events (ICH E9(R1))","aka":["estimand","estimands","estimand framework","ICH E9(R1)","E9(R1)","intercurrent event","intercurrent events","treatment policy strategy","treatment policy estimand","hypothetical strategy","hypothetical estimand","composite strategy","while on treatment strategy","principal stratum","principal stratum strategy","sensitivity analysis","sensitivity analyses","missing data","missing data handling","handling of missing data","discontinued treatment","treatment discontinuation","rescue medication","subsequent anticancer therapy","what the trial is estimating"],"tldr":"An estimand is a precise statement of what question a trial is answering, including what to do about patients who switch treatment, stop early or start another drug; the ICH E9(R1) framework makes trials write this down before they start.","summary":"Two trials can measure the same endpoint and answer different questions. If a control patient crosses over to the experimental drug at progression, does the overall survival comparison ask what happens under the policy of assigning the drug (whatever patients later receive), or what would have happened had nobody crossed over? If a patient stops the drug for toxicity, is their later progression counted against the drug, or is the question about the effect while on treatment? These things that happen after randomisation and change what is measured are called intercurrent events, and the estimand framework in the 2019 addendum ICH E9(R1) requires a trial to name, for each one, the strategy it will use: treatment policy (count everything that happens, the classic intention-to-treat approach), hypothetical (estimate what would have happened without the event, as crossover adjustment does), composite (treat the event as part of the outcome), while-on-treatment, or principal stratum (restrict to the patients in whom the event would not occur under either arm).\n\nThe framework turns familiar arguments into explicit choices. The crossover debate over VISION and PSMAfore, where most control patients received the radioligand at progression, is a disagreement about estimands: the treatment policy estimand showed little overall survival difference, and the hypothetical estimand estimated by crossover-adjustment methods showed a larger one, and each answers a legitimate but different question. Intention-to-treat and per-protocol analyses in a non-inferiority trial such as PERSEPHONE are two estimands for the same data. Trials that add a new drug on top of a control that patients may later receive anyway, as in many adjuvant designs, are asking a treatment-policy question whether they say so or not.\n\nFor readers the practical use is a checklist: what population, what variable, what happens to the number when patients switch, stop or are lost, and what summary (a hazard ratio, a difference in proportions at a landmark) is reported. A trial that states its estimand in the protocol and reports sensitivity analyses under the alternatives is harder to spin than one that picks the most flattering analysis after the fact. Regulators now expect the estimand to be specified for the primary endpoint of every confirmatory trial.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Estimand","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estimand"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["crossover"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials","route":"/terms/estimand/"}
{"id":"gray-unit","kind":"term","name":"Gray unit (Gy)","aka":["cGy","centigray","EQD2","BED","biologically effective dose","dose escalation","dose-escalated","radiation dose","absorbed dose","prescribed dose","total dose","60 Gy","70 Gy","GBq","MBq","becquerel"],"tldr":"The unit of radiation dose absorbed by tissue: one gray is one joule per kilogram. A curative course is typically 50-70 Gy in total; a single bone-pain treatment is 8 Gy. Radiopharmaceuticals are prescribed by activity in becquerels (GBq) instead.","summary":"Because biological effect depends on both total dose and dose per fraction, different schedules are compared with the equivalent dose in 2 Gy fractions (EQD2) or biologically effective dose (BED); cervical brachytherapy aims for ≥85 Gy EQD2, early lung SBRT for BED ≥100 Gy. Dose escalation beyond 60 Gy did not help in stage III lung cancer (RTOG 0617) but did in prostate cancer. For radioligand therapy the administered activity (7.4 GBq of 177Lu-PSMA-617) is fixed, and dosimetry estimates the resulting gray to tumour and kidneys. Whole-body doses above about 4 Gy are lethal without marrow rescue, which is the basis of total body irradiation conditioning.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gray_(unit)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gray_(unit)"}],"tags":[],"related":["dosimetry","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/gray-unit/"}
{"id":"half-life","kind":"term","name":"Half-life","aka":["half-lives","half life","plasma half-life","elimination half-life","pharmacokinetics","pharmacokinetic","PK","cleared from the body","drug exposure","peak concentration","Cmax","AUC","steady state","steady-state"],"tldr":"The time it takes for the amount of a drug in the blood to fall by half. It sets how often a drug must be given: hours to a day for small molecules such as kinase inhibitors, so they are taken daily, and two to four weeks for antibodies, so they are given every three or six weeks.","summary":"Small molecules are typically cleared by the liver and kidneys within hours to a day, so kinase inhibitors are taken daily; antibodies are protected from breakdown by recycling receptors and persist for two to four weeks, allowing dosing every three or six weeks. Half-life shapes both benefit and harm: a long-lived checkpoint inhibitor keeps working, and keeps causing immune side effects, for months after the last dose, while a radioactive drug's physical half-life (6.6 days for lutetium-177, 10 days for actinium-225) determines how long it irradiates the tumour. Pharmacokinetics is the study of these processes, and matching dose and schedule to them is central to dose optimisation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Biological_half-life","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biological_half-life"}],"tags":[],"related":["alpha-vs-beta","dosimetry","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","route":"/terms/half-life/"}
{"id":"ligand","kind":"term","name":"Ligand","aka":["ligands","binding partner"],"tldr":"The molecule that fits into a receptor and switches it on: growth factors, hormones and cytokines are all ligands. Cancers make their own ligands or mutate receptors so none is needed, and some drugs act on the ligand itself, as bevacizumab does by soaking up VEGF.","summary":"Ligand binding changes the receptor's shape and starts a signal inside the cell; the specificity of the fit is why one growth factor activates one family of receptors. Cancers exploit ligands by making their own (autocrine signalling), by persuading neighbouring cells to make them, or by mutating receptors so they no longer need the ligand at all. Several drugs act on ligands rather than receptors: bevacizumab soaks up VEGF before it can reach its receptor, and 'radioligands' are small molecules or peptides that bind a receptor such as PSMA to deliver radiation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics","route":"/terms/ligand/"}
{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","aka":["castration-resistant","castration resistant","castrate-resistant","mCRPC","nmCRPC","CRPC","castration-sensitive","castration sensitive","hormone-sensitive","hormone sensitive","mHSPC","mCSPC","HSPC","hormone-naive","hormone-refractory","biochemical recurrence","PSA recurrence","rising PSA","PSA progression","rPFS"],"tldr":"Prostate cancer starts out fed by testosterone (hormone-sensitive) and shrinks when it is removed. When it learns to grow despite castrate testosterone levels it is called castration-resistant, a later and more dangerous stage with its own treatments.","summary":"Metastatic hormone-sensitive disease (mHSPC) is treated with androgen deprivation plus an ARPI (abiraterone, enzalutamide, apalutamide, darolutamide) and sometimes docetaxel (STAMPEDE, LATITUDE, ARASENS), which delays castration resistance by years. Castration-resistant disease (CRPC), defined by PSA or radiographic progression with testosterone <50 ng/dL, arises through androgen receptor amplification, mutations, splice variants (AR-V7) and intratumoural androgen synthesis; it is treated with ARPI switch, docetaxel and cabazitaxel, PARP inhibitors for HRR mutations, 177Lu-PSMA-617 (VISION, PSMAfore) and radium-223. Non-metastatic CRPC (rising PSA, clear scans) has its own approvals. Radiographic PFS (rPFS) is the usual endpoint.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer"}],"tags":[],"related":["arpi","lu-177","ra-223"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede","vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/mcrpc-mhspc/"}
{"id":"medicare-ced","kind":"term","name":"Medicare coverage with evidence development","aka":["coverage with evidence development","CED","national coverage determination","national coverage determinations","NCD 90.2","Medicare NGS coverage","Medicare coverage of cancer drugs","protected classes"],"tldr":"Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies.","summary":"United States, agency guidance under the Social Security Act. Coverage with evidence development (CED) lets the Centers for Medicare and Medicaid Services issue a national coverage determination that pays for an item only when the patient is in an approved study or registry, under section 1862(a)(1)(E) of the Social Security Act. CMS set out the policy in 2006 guidance, revised in 2014 and again in 2024. Primary text: the CMS CED page and the Medicare Coverage Database.\n\nOncology examples: FDG-PET for most cancers was covered from 2006 through the National Oncologic PET Registry, which then generated the evidence that led to unrestricted coverage in 2009 and 2013. National coverage determination 90.2 (March 2018, widened in 2020) covers FDA-approved next-generation sequencing companion diagnostics for patients with advanced cancer, and germline testing for hereditary cancer. CAR-T therapy received a national coverage determination in August 2019 after an initial proposal to impose CED was dropped. More broadly, Medicare Part B must cover anti-cancer drugs for uses supported by the statutory compendia, and Part D treats antineoplastics as a protected class, so unlike Europe there is no national decision on whether a cancer drug is worth its price.\n\nThe arguments: CED is praised for turning coverage into evidence and criticised for slow registries that never end; the compendia rule and protected classes are why the United States pays for nearly every approved cancer drug at list price, which the Inflation Reduction Act's negotiation programme begins to change.","asOf":"2026-09-17","links":[{"label":"CMS: coverage with evidence development","url":"https://www.cms.gov/medicare/coverage/evidence"},{"label":"CMS: Medicare Coverage Database","url":"https://www.cms.gov/medicare-coverage-database/"}],"tags":["law","us"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy","route":"/terms/medicare-ced/"}
{"id":"net-grade-ki67","kind":"term","name":"Neuroendocrine tumour grade (Ki-67) and WHO classification","aka":[],"tldr":"How fast the tumour cells are dividing, measured by Ki-67 staining, separates slow-growing neuroendocrine tumours from aggressive neuroendocrine carcinomas and decides the treatment.","summary":"WHO 2019/2022: well-differentiated NET grade 1 (Ki-67 <3%), grade 2 (3-20%), grade 3 (>20%, well-differentiated); poorly differentiated neuroendocrine carcinoma (NEC, small- or large-cell) is a separate lineage treated like small-cell lung cancer. Grade drives choice among somatostatin analogues, PRRT, targeted therapy and chemotherapy.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":[],"related":[],"indications":["neuroendocrine","sclc","grade-3-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology","route":"/terms/net-grade-ki67/"}
{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","aka":[],"tldr":"Cancer that has spread to only a few places, which may still be curable by treating each spot.","summary":"Oligometastatic disease is cancer that has spread to only a few sites, usually no more than three to five metastases, and may still be curable if each spot is treated. The SABR-COMET trial supported metastasis-directed SBRT / SABR (stereotactic radiotherapy), and the ESTRO/EORTC classification distinguishes synchronous, oligorecurrent and oligoprogressive disease, the last covered by the related term Oligoprogression. PSMA PET has expanded detection of this state in Prostate cancer, and the term is also referenced by the Renal cell carcinoma entry and the bottleneck on metastasis biology. Ideas building on it include PSMA-PET-guided metastasis-directed therapy as a curative strategy and a test to tell true oligometastatic disease from hidden widespread spread.","asOf":"2026-09-04","links":[{"label":"NCI Dictionary of Cancer Terms: oligometastasis","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oligometastasis"},{"label":"Lievens et al., Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus (Radiotherapy and Oncology 2020)","url":"https://doi.org/10.1016/j.radonc.2020.04.003"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical","route":"/terms/oligometastatic/"}
{"id":"payload","kind":"term","name":"Payload (ADC)","aka":[],"tldr":"The payload is the poison an ADC carries, usually a chemotherapy far too toxic to give on its own.","summary":"The payload is the cytotoxic warhead conjugated to the antibody. Classes: tubulin inhibitors (MMAE, MMAF, DM1, DM4), topoisomerase-I inhibitors (DXd, SN-38, exatecan, belotecan derivatives), DNA-damaging agents (PBD dimers, calicheamicin, duocarmycin). Newer payloads: degraders, immune agonists, radionuclides. Membrane permeability determines bystander killing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry","route":"/terms/payload/"}
{"id":"pharmacokinetics","kind":"term","name":"Pharmacokinetics (PK), half-life and exposure","aka":["pharmacokinetic","pharmacokinetics","PK/PD","pharmacodynamics","half-life","half life","exposure-response","exposure–response","drug exposure","AUC","Cmax","steady state","steady-state","bioavailability","oral bioavailability","drug-drug interaction","CYP3A4","food effect","therapeutic drug monitoring","TDM","flat dosing","weight-based dosing","body surface area","mg/m²","mg/kg","pharmacodynamic"],"tldr":"How a drug moves through the body: how much is absorbed, how high the blood level gets, how long it lasts (half-life) and how it is cleared. These numbers decide the dose, the schedule and whether a pill can be taken with food or other medicines.","summary":"Antibodies have half-lives of 2-4 weeks and are dosed every 2-6 weeks, often now at flat doses (pembrolizumab 400 mg q6w) rather than by weight; small molecules are dosed daily and interact with CYP3A4 inhibitors, acid suppressants and food; chemotherapy is dosed by body surface area with organ-function adjustments. Exposure-response analyses link drug levels to efficacy and toxicity and underpin Project Optimus's push to find optimal rather than maximal doses; therapeutic drug monitoring is used for busulfan, methotrexate and increasingly for TKIs. Radiopharmaceutical PK determines tumour versus kidney and marrow dose (dosimetry). Poor oral bioavailability has ended more than one promising drug's development.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pharmacokinetics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacokinetics"}],"tags":[],"related":["dosimetry"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/pharmacokinetics/"}
{"id":"prostatectomy","kind":"term","name":"Radical prostatectomy","aka":["prostatectomy","robotic prostatectomy","robot-assisted prostatectomy","prostatectomies"],"tldr":"Removing the entire prostate gland and seminal vesicles for localised prostate cancer, now almost always with a robot.","summary":"One of three options for localised disease alongside radiotherapy and active surveillance; ProtecT showed identical 15-year prostate cancer mortality (~3%) across all three. Robot-assisted laparoscopic prostatectomy dominates in high-income countries with nerve-sparing techniques to reduce erectile dysfunction, but incontinence (5-20%) and impotence (30-70%) remain the main harms. PSA should become undetectable; a rise afterwards (biochemical recurrence) is imaged with PSMA PET and treated with salvage radiotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostatectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostatectomy"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures","route":"/terms/prostatectomy/"}
{"id":"prrt-term","kind":"term","name":"PRRT (peptide receptor radionuclide therapy)","aka":["PRRT","peptide receptor radionuclide therapy","177Lu-DOTATATE","lutetium DOTATATE","DOTATATE","DOTATOC","somatostatin analogue","somatostatin analogues","SSA","SSAs","SSTR-targeted","SSTR imaging","somatostatin receptor imaging","alpha PRRT"],"tldr":"A radioactive drug for neuroendocrine tumours: a small peptide that homes to the somatostatin receptor on the tumour cells carries lutetium-177, which irradiates them from within. Given four times, two months apart.","summary":"Neuroendocrine tumours overexpress somatostatin receptor 2, imaged with gallium-68 or copper-64 DOTATATE PET and treated first with cold somatostatin analogues (octreotide, lanreotide) for symptom and growth control. 177Lu-DOTATATE (NETTER-1, approved 2018) improved progression-free survival dramatically in midgut NETs and NETTER-2 (2024) moved it to first line in high-grade tumours; 177Lu-edotreotide (COMPETE) followed. Alpha-emitting versions (212Pb-DOTAMTATE, 225Ac-DOTATATE) are in phase 3 for PRRT-refractory disease. Toxicities are marrow suppression, kidney dose and a small risk of MDS. Together with radioiodine and PSMA therapy it defines the theranostic model.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy"}],"tags":[],"related":["prrt","theranostics","dosimetry","radioiodine-therapy","alpha-vs-beta","ga-68","cu-64","lu-177","ac-225","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["sstr2"],"drugs":["ga68-dotatate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/prrt-term/"}
{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","aka":["PSA doubling time","PSADT","PSA velocity","PSA density","PSAD","PSA kinetics","PSA rise","rising PSA","biochemical recurrence PSA threshold","PSA nadir","PSA response","PSA50","PSA90","PSA progression"],"tldr":"How fast PSA is rising matters more than its level: a doubling time under ten months after surgery or radiotherapy, or under nine months in castration-resistant disease, marks the men whose cancer is moving quickly and who benefit from earlier hormone therapy or a PSMA scan, while PSA density (PSA divided by prostate volume) helps decide who needs a biopsy at all.","summary":"What is measured: the rate of change of prostate-specific antigen and its concentration relative to gland size. How: doubling time is calculated by log-linear regression from at least three values over at least three months; density is PSA (ng/mL) divided by prostate volume (mL) on MRI or ultrasound, with 0.15 (0.10 with MRI) the usual threshold. Confounders: 5-alpha-reductase inhibitors halve PSA, prostatitis raises it. What a result changes: after radical prostatectomy a PSA of 0.2 ng/mL or more defines biochemical recurrence, and the EAU splits it into low and high risk by a doubling time of a year or less or a Gleason grade group of 4 or 5, which sets the urgency of salvage radiotherapy and whether hormone therapy is added; PSMA PET is positive in most men above 0.5 ng/mL; in non-metastatic castration-resistant disease a doubling time of ten months or less was the entry criterion for SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), which lengthened metastasis-free and overall survival; a density above 0.15 with a PI-RADS 3 lesion tips towards biopsy, and density is an entry criterion for active surveillance (PRIAS 0.2 or less); in metastatic castration-resistant disease a 50 percent PSA fall (PSA50) is a trial endpoint, and a PSA under 0.2 at seven months of hormone therapy predicts long survival. Where it matters: biochemical recurrence, low-risk, non-metastatic castration-resistant and metastatic castration-resistant prostate cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["psma-pet","enzalutamide"],"indications":["prostate-bcr","prostate-nmcrpc","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","route":"/terms/psa-kinetics/"}
{"id":"psa50","kind":"term","name":"PSA50 / PSA90 response","aka":[],"tldr":"PSA50 is the share of patients whose PSA falls by at least half on treatment, and PSA90 the share whose PSA falls by 90%.","summary":"PSA50 is the proportion of patients whose PSA falls by at least half on treatment, and PSA90 the proportion whose PSA falls by nine tenths or more. Both are standard early-efficacy read-outs in trials of metastatic castration-resistant prostate cancer, reported under the PCWG3 recommendations, and readers meet them in the VISION and TheraP radioligand trials and on the page for xaluritamig. A PSA response correlates with, but does not replace, radiographic progression-free survival and overall survival. The endpoint can also end a development programme early: a PSA90 futility analysis stopped masofaniten's phase 2. The term extends the PSA entry, which describes the underlying marker.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Prostate-specific_antigen","links":[{"label":"PCWG3 trial design recommendations incl. PSA response reporting (Scher et al., J Clin Oncol 2016)","url":"https://doi.org/10.1200/JCO.2015.64.2702"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints","route":"/terms/psa50/"}
{"id":"radiation-necrosis","kind":"term","name":"Radiation necrosis (brain)","aka":[],"tldr":"Death of brain tissue months to years after radiosurgery or high-dose brain radiotherapy, which can look exactly like tumour growing back on a scan.","summary":"Radiation necrosis affects a minority of patients after stereotactic radiosurgery to brain metastases and after high-dose treatment of gliomas, more often with larger volumes and with concurrent immunotherapy or targeted drugs. It causes swelling and symptoms that mimic progression; perfusion MRI, amino-acid PET and sometimes biopsy separate the two. Treatment is steroids, bevacizumab for refractory cases, and occasionally surgery or laser ablation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_necrosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_necrosis"}],"tags":["radiation-wave1"],"related":[],"indications":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","route":"/terms/radiation-necrosis/"}
{"id":"radioiodine-term","kind":"term","name":"Radioiodine therapy (I-131)","aka":["radioiodine","radioactive iodine","radioiodine ablation","radioiodine therapy","I-131","131I","iodine-131","RAI-refractory","radioiodine-refractory","RAI-avid","radioiodine-avid","iodine-avid","iodine uptake","redifferentiation","recombinant TSH","rhTSH"],"tldr":"Swallowing a capsule of radioactive iodine after thyroid surgery: thyroid cells (including cancer cells) are the only ones that soak up iodine, so the radiation destroys leftover thyroid tissue and metastases while sparing everything else. It was the first targeted radiotherapy, in 1946.","summary":"Differentiated (papillary and follicular) thyroid cancer retains iodine uptake, so I-131 ablates remnant tissue after total thyroidectomy in intermediate- and high-risk patients and treats iodine-avid metastases; low-risk patients no longer need it (ESTIMABL2, IoN). Thyroglobulin and whole-body scans monitor for recurrence. 'Radioiodine-refractory' disease (about 5-15%, more in poorly differentiated and BRAF-mutant tumours) is treated with lenvatinib, sorafenib or targeted drugs for RET, NTRK and BRAF alterations, and MEK/BRAF inhibitors can restore iodine uptake ('redifferentiation'). Side effects are salivary gland damage, dry mouth and a small excess of secondary cancers at high cumulative doses.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Iodine-131","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iodine-131"}],"tags":[],"related":["radioiodine-therapy","theranostics","prrt","i-131"],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/radioiodine-term/"}
{"id":"radiotherapy","kind":"term","name":"Radiotherapy","aka":["radiation therapy","radiation treatment","radiation","irradiation","irradiated","radiotherapy fractions","fractionation","hypofractionated","chemoradiotherapy","chemoradiation","radiation oncology","radiation oncologist","radiosensitiser","radiosensitizer","radiosensitive","radioresistant","external beam","radiation oncologists","radiosensitisers"],"tldr":"Using high-energy X-rays or particles to damage the DNA of cancer cells in a precisely aimed volume of the body. On its own it cures early prostate, larynx, cervix and skin cancers, it is combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and about half of all cancer patients receive it.","summary":"Modern radiotherapy shapes beams to the tumour from several angles (IMRT, image-guided and stereotactic techniques) so that the tumour gets a lethal dose while surrounding tissue gets much less; treatment is usually split into daily fractions over one to seven weeks to let normal tissue repair, though ultra-short courses (SBRT) are increasingly used. It is a local therapy, curative on its own in early prostate, larynx, cervix and skin cancers, combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and used after surgery to sterilise the operative bed. Protons and carbon ions spare more normal tissue; radiation may also help immunotherapy by releasing tumour antigens (the abscopal effect), and radioligand therapy delivers radiation internally through a targeting molecule.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics","route":"/terms/radiotherapy/"}
{"id":"sdh-deficiency","kind":"term","name":"SDH deficiency (SDHB immunohistochemistry loss)","aka":["SDH-deficient","SDH-deficient GIST","SDHB immunohistochemistry","SDHB loss","SDHB-negative","SDHx","SDHx mutation","SDHA","SDHC epimutation","SDHC promoter methylation","succinate dehydrogenase deficiency","Carney-Stratakis syndrome","Carney triad","KIT/PDGFRA wild-type GIST","hereditary paraganglioma syndrome","SDH-deficient renal cell carcinoma"],"tldr":"Loss of the succinate dehydrogenase enzyme, shown by a negative SDHB stain, marks a small family of tumours (some stomach GISTs, paragangliomas and phaeochromocytomas, a rare kidney cancer) that are often inherited, occur in young people, ignore imatinib and grow slowly; the stain is the trigger for germline testing of the whole family.","summary":"What is measured: loss of the mitochondrial succinate dehydrogenase complex. How: SDHB immunohistochemistry on the tumour (loss of granular cytoplasmic staining whichever subunit is mutated; SDHA staining is lost only with SDHA mutation), followed by germline and tumour sequencing of SDHA, SDHB, SDHC, SDHD and SDHAF2 and, if negative, testing for SDHC promoter methylation (the epimutation behind the Carney triad). Where it occurs: 5 to 7 percent of GISTs (almost all gastric, in young and often female patients, multifocal, epithelioid, with nodal metastases and an indolent course; Carney-Stratakis syndrome pairs them with paragangliomas), 30 to 40 percent of paragangliomas and phaeochromocytomas (SDHB carriers have the highest metastatic risk), SDH-deficient renal cell carcinoma and some pituitary adenomas. What a result changes: an SDH-deficient GIST does not respond to imatinib because it does not depend on KIT, sunitinib and regorafenib help modestly, temozolomide is under study because of the tumours' hypermethylation, surgery is kept conservative because multifocality and nodal disease are the rule, and follow-up is lifelong; a germline finding leads to cascade testing, whole-body MRI surveillance every two to three years and plasma metanephrines; metastatic paraganglioma is treated with lutetium-177 DOTATATE or iodine-131 MIBG, and HIF-2 alpha inhibitors such as belzutifan are in trials. Where it matters: GIST, imatinib-resistant GIST and the rare childhood cancers page.","asOf":"2026-09-17","links":[],"tags":[],"related":["sunitinib","temozolomide","lutathera","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers","route":"/terms/sdh-deficiency/"}
{"id":"sentinel-lymph-node-biopsy","kind":"term","name":"Sentinel node biopsy","aka":["sentinel lymph node biopsy","sentinel lymph node","sentinel node","sentinel lymph node mapping","SLNB"],"tldr":"Finding and removing the first one or two lymph nodes a tumour drains to, to see whether cancer has spread, instead of removing the whole nodal basin.","summary":"A dye or radioactive tracer (technetium tilmanocept, indocyanine green, blue dye) injected at the tumour travels to the 'sentinel' node, which is removed and examined. If it is clear, the remaining nodes are almost certainly clear and a full dissection with its lymphoedema risk is avoided. Standard in breast cancer, melanoma (from ~0.8 mm Breslow), endometrial and vulval cancers and increasingly oral cavity cancer; even positive sentinel nodes often no longer trigger full axillary dissection (Z0011, SENOMAC).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Sentinel_lymph_node","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"}],"tags":[],"related":["tilmanocept-tc99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures","route":"/terms/sentinel-lymph-node-biopsy/"}
{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","aka":[],"tldr":"The standardised uptake value (SUV) is a number for how brightly a spot lights up on a PET scan.","summary":"The standardised uptake value (SUV) is the number radiologists use to say how brightly a spot lights up on a PET scan. It is tissue radioactivity normalised to the injected dose and body weight, and SUVmax is the most widely used version. Values are affected by the scanner, the uptake time and blood glucose, and the PERCIST response criteria use SUL, a lean-body variant, instead. The term belongs to the PET (positron emission tomography) and FDG PET technology entries and to the Fludeoxyglucose F-18 (FDG) drug record, and it is referenced by the Cancer metabolism pathway, the Warburg effect, the Society of Nuclear Medicine and Molecular Imaging, and ideas on de-acidifying tumours so T cells can work and on a phase 0 fund using microdoses and imaging.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Standardized_uptake_value","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Standardized_uptake_value"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging","route":"/terms/suv/"}
{"id":"tare","kind":"term","name":"TARE / SIRT (radioembolisation with yttrium-90)","aka":["TARE","SIRT","radioembolisation","radioembolization","Y-90","Y90","yttrium-90","selective internal radiation therapy","90Y microspheres"],"tldr":"Injecting tiny radioactive glass or resin beads into the liver's artery so they lodge in the tumour and irradiate it from inside.","summary":"Yttrium-90 microspheres (20-60 µm) deliver beta radiation over a few millimetres with a 64-hour half-life, treating hepatocellular carcinoma, colorectal liver metastases and neuroendocrine liver metastases. Randomised trials against sorafenib (SARAH, SIRveNIB) showed no survival gain but better tolerability; radiation segmentectomy, which delivers ablative doses to a small segment, achieves outcomes close to ablation. Dosimetry now individualises the activity (DOSISPHERE). Chosen over TACE when portal vein thrombus is present.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy"}],"tags":[],"related":["y-90"],"indications":["hcc","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures","route":"/terms/tare/"}
{"id":"theranostics","kind":"term","name":"Theranostics","aka":["theranostic"],"tldr":"Using the same targeting molecule for a diagnostic scan and a therapy, so you treat exactly what you can see.","summary":"Theranostics uses the same targeting molecule for a diagnostic scan and for therapy, so clinicians treat exactly what they can see. The established pairs are gallium-68 or fluorine-18 PSMA imaging with lutetium-177 or actinium-225 PSMA therapy, gallium-68 DOTATATE with lutetium-177 DOTATATE, and iodine-123 with iodine-131, and one chemistry thereby enables patient selection, dosimetry and response assessment. The concept links the Radioligand therapy (beta emitters), Targeted alpha therapy and PSMA PET technologies with Somatostatin receptor PET, Radioiodine therapy and the pairings PSMA PET to PSMA radioligand therapy and SSTR PET to PRRT. It is referenced by the Prostate cancer, Thyroid cancer and Neuroendocrine tumours entries and by Clarity Pharmaceuticals.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Theranostics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Theranostics"}],"tags":[],"related":["f-18","ga-68","i-123","lu-177","ac-225","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","psma-pet","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon","route":"/terms/theranostics/"}
{"id":"thrombocytopenia","kind":"term","name":"Thrombocytopenia","aka":["thrombocytopaenia","low platelets","platelet count","platelet transfusion","bleeding risk","grade 3-4 thrombocytopenia","immune thrombocytopenia","ITP","thrombopoietin receptor agonist","platelet transfusions"],"tldr":"Too few platelets, the blood cells that form clots, caused by chemotherapy or by the cancer in the marrow. Mild cases cause bruising; severe cases (under 10-20 × 10⁹/L) risk serious bleeding and need platelet transfusions.","summary":"Common with carboplatin, gemcitabine, temozolomide, lurbinectedin, PARP inhibitors (niraparib especially), radioligand therapies and in leukaemia and myeloma; it limits dose more often than neutropenia for some regimens because no growth factor is routinely used (romiplostim and avatrombopag are being trialled). Grade 4 is <25 × 10⁹/L. It also complicates anticoagulation for cancer-associated thrombosis and procedures such as biopsies and central line placement. Cirrhosis with portal hypertension causes chronic thrombocytopenia that constrains liver cancer treatment, and immune thrombocytopenia is an immune-related adverse event of checkpoint inhibitors.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Thrombocytopenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Thrombocytopenia"}],"tags":[],"related":["cytopenias","anaemia"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects","route":"/terms/thrombocytopenia/"}
{"id":"tumour-hypoxia","kind":"term","name":"Tumour hypoxia","aka":[],"tldr":"Regions of a tumour that have outgrown their blood supply and are short of oxygen. They resist radiotherapy and some chemotherapy, and drive the tumour to become more aggressive.","summary":"Fast-growing tumours have chaotic, leaky blood vessels, leaving pockets of cells living on very little oxygen. Hypoxic cells need up to three times the radiation dose to be killed, switch on HIF-driven survival programmes, become more invasive and are selected for genomic instability. Hypoxia can be imaged with PET tracers, measured by gene signatures and targeted with sensitisers, hypoxia-activated drugs, hyperthermia and dose escalation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tumor_hypoxia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_hypoxia"}],"tags":["radiation-wave1"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics","route":"/terms/tumour-hypoxia/"}
{"id":"action-1","kind":"trial","name":"ACTION-1","aka":[],"tldr":"Tests whether an actinium alpha-radioligand rescues neuroendocrine tumours after lutetium therapy fails.","summary":"ACTION-1, trial NCT05477576 sponsored by Bristol Myers Squibb through RayzeBio, tests whether the actinium-225 alpha-radioligand RYZ101, or 225Ac-DOTATATE, rescues somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumours after lutetium-177 somatostatin analogue therapy has failed. Its phase 1b established a fixed dose of 10.2 MBq with encouraging responses, the phase 3 against investigator's choice has closed enrolment (ClinicalTrials.gov status active, not recruiting, 343 participants actual, record updated 5 October 2026; primary completion estimated December 2026), and its dosimetry was published in the Journal of Nuclear Medicine in 2026. Nuclide links it to targeted alpha therapy, actinium-225 DOTATATE, lutetium-177 dotatate and the pairing of beta then alpha PRRT. Whether an alpha emitter can overcome resistance to a beta emitter aimed at the same receptor is the question it will answer.","status":"active","asOf":"2026-10-11","links":[{"label":"ClinicalTrials.gov NCT05477576","url":"https://clinicaltrials.gov/study/NCT05477576"},{"label":"ACTION-1 dosimetry (JNM 2026)","url":"https://jnm.snmjournals.org/content/67/8/1239"}],"tags":[],"related":["lu-177","ac-225"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":["ryz101","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05477576","phase":"3","setting":"SSTR-positive GEP-NETs progressing after 177Lu somatostatin-analogue therapy: 225Ac-DOTATATE (RYZ101) vs investigator's choice","sponsor":"BMS (RayzeBio)","enrolled":343,"enrolledBasis":"registry","outcomes":[],"route":"/trials/action-1/"}
{"id":"ahod2131","kind":"trial","name":"AHOD2131 (COG / NCTN)","aka":[],"tldr":"Asks whether early-stage Hodgkin lymphoma in children and adults can be treated with immunotherapy instead of some chemotherapy and radiation.","summary":"AHOD2131, trial NCT05675410 run by the Children's Oncology Group and the NCI, asks whether early-stage classical Hodgkin lymphoma in children and adults aged 5 to 60 can be treated with brentuximab vedotin plus nivolumab in a response-adapted design, instead of some chemotherapy and radiation. It uses PET after two cycles to steer therapy, has progression-free survival as its primary endpoint, measures late effects, and is ongoing with no results yet. Nuclide links it to Hodgkin lymphoma, PET-adapted therapy, brentuximab vedotin, nivolumab, the Children's Oncology Group, Kara M. Kelly, the idea of chemotherapy-free early-stage Hodgkin treatment and the S1826 paper. Whether immunotherapy can spare young patients the late effects of chemotherapy and radiation without losing cures is the question it exists to answer.","status":"recruiting","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05675410","url":"https://clinicaltrials.gov/study/NCT05675410"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-adapted-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05675410","phase":"3","setting":"Newly diagnosed stage I-II classical Hodgkin lymphoma, age 5-60: standard therapy vs brentuximab vedotin + nivolumab (response-adapted), with or without radiation","sponsor":"Children's Oncology Group / NCI","enrolledBasis":"registry","outcomes":[],"route":"/trials/ahod2131/"}
{"id":"alphabreak","kind":"trial","name":"AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","aka":[],"tldr":"The actinium-225 PSMA trials that will help decide whether alpha-emitting PSMA drugs become the next step after Pluvicto.","summary":"AlphaBreak and AcTION, led by trial NCT06402331, are the trials that will help decide whether alpha-emitting PSMA drugs become the next step after Pluvicto in PSMA-positive metastatic castration-resistant prostate cancer. AlphaBreak tests FPI-2265, an actinium-225 PSMA-I&T agent from AstraZeneca and Fusion, after lutetium PSMA therapy, while Novartis' AcTION programme tests actinium-225 PSMA-617 in post-lutetium and lutetium-naive settings, and Bayer's PAnTHA phase 1 of 225Ac-PSMA-Trillium reported at ASCO GU 2026. ClinicalTrials.gov lists AlphaBreak (NCT06402331) as phase 2, active and no longer recruiting, with an actual enrolment of 110 (registry record last updated 8 April 2026). Nuclide links them to targeted alpha therapy, the actinium-225 PSMA agents record, and to Fusion, AstraZeneca, Novartis and Bayer. AlphaBreak has stopped recruiting and has posted no results; dry mouth and actinium-225 supply are the constraints, and whether alpha emitters help after lutetium is the question they exist to answer.","status":"active","asOf":"2026-09-27","links":[{"label":"ClinicalTrials.gov NCT06402331","url":"https://clinicaltrials.gov/study/NCT06402331"}],"tags":[],"related":["ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":["ac225-psma"],"companies":["fusion-pharma","astrazeneca","novartis","bayer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06402331","phase":"2","setting":"PSMA-positive mCRPC: actinium-225 PSMA radioligands vs standard of care, including after 177Lu-PSMA","sponsor":"AstraZeneca (Fusion); Novartis","enrolled":110,"enrolledBasis":"registry","outcomes":[],"replication":"Ongoing phase 2 of 225Ac-PSMA-I&T after 177Lu-PSMA (ClinicalTrials.gov: active, not recruiting, 110 enrolled); no results.","route":"/trials/alphabreak/"}
{"id":"alphamedix-02","kind":"trial","name":"ALPHAMEDIX-02","aka":[],"tldr":"An alpha-emitting radioligand met all its primary endpoints, with responses in more than half of patients new to radioligand therapy.","summary":"ALPHAMEDIX-02, trial NCT05153772 sponsored by RadioMedix, Orano Med and Sanofi and reported in 2025, showed that the alpha-emitting radioligand 212Pb-DOTAMTATE met all its primary endpoints, with responses in more than half of patients with somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumours who were new to radioligand therapy. In the single-arm phase 2 the objective response rate in PRRT-naive patients was 54.3 percent, most were still progression-free around three years, and the PRRT-exposed cohort was largely progression-free at eighteen months, as Sanofi reported in October 2025; the drug holds Breakthrough Therapy designation and the registrational path is being finalised. Nuclide links it to targeted alpha therapy, PRRT, 212Pb-DOTAMTATE and the pairing of beta then alpha PRRT. Whether a randomised trial confirms superiority over lutetium is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05153772","url":"https://clinicaltrials.gov/study/NCT05153772"},{"label":"Sanofi press release","url":"https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053"}],"tags":[],"related":["pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy","prrt"],"targets":[],"drugs":["alphamedix"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05153772","phase":"2","setting":"Unresectable or metastatic SSTR-positive GEP-NETs, PRRT-naive and PRRT-exposed cohorts: 212Pb-DOTAMTATE single arm","sponsor":"RadioMedix / Orano Med / Sanofi","result":"ORR 54.3% (PRRT-naive); all primary endpoints met.","yearReported":2025,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate (PRRT-naive)","primary":true,"unit":"%","arms":[{"name":"212Pb-DOTAMTATE","value":54.3}],"source":"https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053"}],"route":"/trials/alphamedix-02/"}
{"id":"alsympca","kind":"trial","name":"ALSYMPCA","aka":[],"tldr":"ALSYMPCA is the trial that won approval for the first alpha-emitting drug.","summary":"ALSYMPCA, trial NCT00699751 sponsored by Bayer and Algeta and reported in 2013, is the trial that won approval for radium-223, the first alpha-emitting drug. It randomised 921 men with symptomatic bone-metastatic castration-resistant prostate cancer and no visceral disease to radium-223 or placebo, met its primary overall survival endpoint and reduced skeletal events. Nuclide links it to prostate cancer, targeted alpha therapy, radium-223 dichloride, A. Oliver Sartor and Karim Fizazi; it was a single pivotal trial, and the later ERA 223 combination with abiraterone was harmful, so use is now restricted to monotherapy in bone-predominant disease. Whether targeted alpha emitters such as actinium-225 PSMA agents can go further than a bone-seeking radium ever could is the question its legacy poses. Radium-223 has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT00699751","url":"https://clinicaltrials.gov/study/NCT00699751"}],"tags":[],"related":["ac-225","ra-223"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":["radium-223"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oliver-sartor","karim-fizazi"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00699751","phase":"3","setting":"Symptomatic bone-metastatic CRPC without visceral disease: radium-223 vs placebo","sponsor":"Bayer / Algeta","result":"OS HR 0.70.","yearReported":2013,"enrolled":921,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Radium-223","n":614,"value":14.9},{"name":"Placebo","n":307,"value":11.3}],"hr":0.7,"ci":[0.58,0.83],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1213755"}],"replication":"Single pivotal trial; the ERA 223 combination with abiraterone was harmful, so use is now restricted to monotherapy in bone-predominant disease.","route":"/trials/alsympca/"}
{"id":"anbl1531","kind":"trial","name":"COG ANBL1531","aka":[],"tldr":"COG ANBL1531 is the current North American high-risk trial, adding targeted radiation during induction and an ALK pill for children whose tumours carry ALK mutations.","summary":"COG ANBL1531, trial NCT03126916 run by the Children's Oncology Group, is the current North American trial for newly diagnosed high-risk neuroblastoma, adding iodine-131 MIBG targeted radiation during induction in a randomised comparison for MIBG-avid tumours and the ALK inhibitor lorlatinib in a non-randomised arm for children whose tumours carry ALK aberrations. It also tests reduced-intensity therapy in the standard arm and tracks uptake of eflornithine maintenance, with the primary MIBG randomisation results expected in 2026 to 2027 and encouraging response rates reported from the lorlatinib arm. Nuclide links it to paediatric neuroblastoma, MIBG imaging and therapy, ALK as a target, 131I-MIBG therapy, lorlatinib, the Children's Oncology Group and Yael P. Mossé. Whether targeted radiation during induction improves cure rates is the question it will answer.","status":"active","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03126916","url":"https://clinicaltrials.gov/study/NCT03126916"}],"tags":[],"related":["i-131"],"indications":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":["mibg-theranostics"],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03126916","phase":"3","setting":"Newly diagnosed high-risk neuroblastoma: 131I-MIBG added to induction (randomised, MIBG-avid); lorlatinib added for ALK-aberrant tumours (non-randomised arm)","sponsor":"Children's Oncology Group","enrolledBasis":"registry","outcomes":[],"route":"/trials/anbl1531/"}
{"id":"astra","kind":"trial","name":"ASTRA","aka":[],"tldr":"Adding a MEK inhibitor to boost iodine uptake before ablation did not improve complete remission rates, cooling the 'redifferentiation for everyone' idea.","summary":"ASTRA, trial NCT01843062 sponsored by AstraZeneca and reported in 2019, found that adding the MEK inhibitor selumetinib to boost iodine uptake before adjuvant radioiodine in high-risk differentiated thyroid cancer did not improve complete remission rates, cooling the idea of redifferentiation for everyone. It enrolled 400 patients and randomised 233 of them 2:1 to selumetinib or placebo with radioiodine (Ho and colleagues, Journal of Clinical Oncology 2022) and found no difference in complete remission at eighteen months. Nuclide links it to thyroid cancer, radioiodine therapy, kinase inhibitors, the MAPK pathway and the pairing of MAPK inhibitor redifferentiation followed by radioiodine. Redifferentiation remains reserved for selected radioiodine-refractory patients, where small series show MEK or BRAF and MEK inhibitors restore uptake in about half, and whether that selected use can be proved in a randomised trial is the open question.","status":"negative","asOf":"2026-09-27","links":[{"label":"Ho et al., J Clin Oncol 2022: selumetinib plus adjuvant radioactive iodine (ASTRA)","url":"https://doi.org/10.1200/JCO.21.00714"},{"label":"ClinicalTrials.gov NCT01843062","url":"https://clinicaltrials.gov/study/NCT01843062"},{"label":"JCO 2022","url":"https://ascopubs.org/doi/10.1200/JCO.21.00714"}],"tags":["failure","lesson:adjuvant-vs-active-disease"],"related":[],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01843062","phase":"3","setting":"High-risk differentiated thyroid cancer: selumetinib + adjuvant radioiodine vs placebo + radioiodine","sponsor":"AstraZeneca","result":"Complete remission 40% vs 38.5%; not significant.","yearReported":2019,"enrolled":233,"enrolledBasis":"registry","outcomes":[{"endpoint":"Complete remission at 18 months","primary":true,"unit":"%","arms":[{"name":"Selumetinib + RAI","value":40},{"name":"Placebo + RAI","value":38.5}],"source":"https://ascopubs.org/doi/10.1200/JCO.21.00714"}],"replication":"Small redifferentiation series remain positive in refractory patients; the adjuvant setting was negative.","route":"/trials/astra/"}
{"id":"cabinet","kind":"trial","name":"CABINET (Alliance A021602)","aka":[],"tldr":"Cabozantinib tripled the time without progression in neuroendocrine tumours that had outgrown other treatments, leading to a 2025 approval.","summary":"CABINET, Alliance trial A021602, NCT03375320, sponsored by the Alliance, the NCI and Exelixis and reported in the New England Journal of Medicine in 2024, showed that cabozantinib roughly tripled the time without progression in neuroendocrine tumours that had outgrown other treatments, leading to FDA approval in March 2025. It randomised 298 patients in separate pancreatic and extra-pancreatic cohorts to cabozantinib or placebo and met its primary progression-free survival endpoint in both, with an ESMO 2025 subgroup analysis showing a large reduction in progression risk in lung and thymic tumours. Nuclide links it to neuroendocrine tumours, cabozantinib and the Alliance for Clinical Trials in Oncology. Whether cabozantinib's benefit holds against, or in sequence with, radioligand therapy is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03375320","url":"https://clinicaltrials.gov/study/NCT03375320"},{"label":"ESMO 2025 subgroup (Exelixis)","url":"https://businesswire.com/news/home/20251016096352/en/Exelixis-Announces-Results-from-Subgroup-Analysis-of-CABINET-Phase-3-Pivotal-Trial-Evaluating-CABOMETYX-cabozantinib-in-Advanced-Lung-and-Thymic-Neuroendocrine-Tumors-at-ESMO-2025"}],"tags":[],"related":[],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net","lung-net"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03375320","phase":"3","setting":"Previously treated advanced pancreatic (n=95) and extra-pancreatic (n=203) NETs: cabozantinib vs placebo","sponsor":"Alliance / NCI / Exelixis","result":"PFS HR 0.23 (pNET), 0.38 (epNET).","yearReported":2024,"enrolled":298,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (pancreatic NET)","primary":true,"unit":"months","arms":[{"name":"Cabozantinib","value":13.8},{"name":"Placebo","value":4.4}],"hr":0.23,"ci":[0.12,0.42],"source":"https://doi.org/10.1056/NEJMoa2403991"},{"endpoint":"Progression-free survival (extra-pancreatic NET)","primary":true,"unit":"months","arms":[{"name":"Cabozantinib","value":8.4},{"name":"Placebo","value":3.9}],"hr":0.38,"ci":[0.25,0.59],"source":"https://doi.org/10.1056/NEJMoa2403991"}],"route":"/trials/cabinet/"}
{"id":"chaarted","kind":"trial","name":"CHAARTED (E3805)","aka":[],"tldr":"The first trial to show chemotherapy at the start of hormone therapy prolongs life in metastatic prostate cancer.","summary":"CHAARTED, ECOG-ACRIN trial E3805, NCT00309985, reported in 2015, was the first trial to show that giving docetaxel at the start of hormone therapy prolongs life in metastatic hormone-sensitive prostate cancer. It randomised 790 men to androgen deprivation with or without docetaxel and met its primary overall survival endpoint, but in long-term follow-up the benefit was confined to men with high-volume disease. Nuclide links it to prostate cancer, docetaxel and Christopher J. Sweeney, and the result was replicated by arm C of the STAMPEDE platform, with the concentration of benefit in high-volume disease shaping how that distinction is used. Whether chemotherapy still earns its place now that triplet regimens and PSMA radioligands have entered this setting is the open question. Docetaxel has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT00309985","url":"https://clinicaltrials.gov/study/NCT00309985"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc"],"sections":[],"technologies":[],"targets":[],"drugs":["docetaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00309985","phase":"3","setting":"Metastatic hormone-sensitive prostate cancer: ADT + docetaxel vs ADT","sponsor":"ECOG-ACRIN","result":"OS HR 0.61 overall; high-volume HR 0.63; low-volume no benefit.","yearReported":2015,"enrolled":790,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"ADT + docetaxel","n":397,"value":57.6},{"name":"ADT alone","n":393,"value":44}],"hr":0.61,"ci":[0.47,0.8],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1503747"}],"replication":"Replicated by STAMPEDE arm C; benefit concentrated in high-volume disease.","route":"/trials/chaarted/"}
{"id":"compete","kind":"trial","name":"COMPETE","aka":[],"tldr":"The first head-to-head trial of a radioligand against a targeted pill in neuroendocrine tumours; the radioligand won on progression-free survival.","summary":"COMPETE, trial NCT03049189 sponsored by ITM Isotope Technologies Munich and published in the Lancet in 2025, was the first head-to-head trial of a radioligand against a targeted tablet in neuroendocrine tumours, and the radioligand won on progression-free survival. It randomised 309 patients with progressive grade 1 to 2 somatostatin-receptor-positive gastroenteropancreatic tumours to 177Lu-edotreotide or everolimus, met its primary progression-free survival endpoint with a significantly higher response rate, and showed an interim overall survival trend that was not significant; the result supports an FDA filing with a PDUFA date of 28 August 2026. Nuclide links it to peptide receptor radionuclide therapy, somatostatin receptor 2, 177Lu-edotreotide, everolimus and Jonathan R. Strosberg. Whether a second lutetium agent differentiates from lutetium dotatate is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03049189","url":"https://clinicaltrials.gov/study/NCT03049189"},{"label":"CancerNetwork: COMPETE","url":"https://www.cancernetwork.com/view/itm-11-demonstrates-superior-pfs-vs-everolimus-in-sstr-gep-nets"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":["prrt"],"targets":["sstr2"],"drugs":["itm-11","everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jonathan-strosberg"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03049189","phase":"3","setting":"Progressive grade 1-2 SSTR-positive GEP-NETs: 177Lu-edotreotide vs everolimus","sponsor":"ITM Isotope Technologies Munich","result":"PFS 23.9 vs 14.1 months, HR 0.67.","yearReported":2025,"enrolled":324,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-edotreotide","n":207,"value":23.9},{"name":"Everolimus","n":102,"value":14.1}],"hr":0.67,"ci":[0.48,0.95],"p":"0.022","source":"https://doi.org/10.1016/S0140-6736(26)00604-5"},{"endpoint":"Overall survival (interim)","unit":"months","arms":[{"name":"177Lu-edotreotide","value":63.4},{"name":"Everolimus","value":58.7}],"hr":0.78,"ci":[0.5,1.1],"p":"0.206","source":"https://doi.org/10.1016/S0140-6736(26)00604-5"}],"route":"/trials/compete/"}
{"id":"decision-sorafenib","kind":"trial","name":"DECISION","aka":[],"tldr":"The first drug approved for thyroid cancers that stopped responding to radioactive iodine.","summary":"DECISION, trial NCT00984282 sponsored by Bayer and reported in 2013, produced the first drug approved for differentiated thyroid cancers that stopped responding to radioactive iodine. It randomised 417 patients to sorafenib or placebo and met its primary progression-free survival endpoint, leading to FDA approval in November 2013, with hand-foot skin reaction and fatigue common. Nuclide links it to thyroid cancer, kinase inhibitors, VEGF and BRAF as targets, the radioiodine-refractory term and Marcia S. Brose, and SELECT confirmed the class effect with a larger benefit for lenvatinib. Sorafenib has been largely displaced by lenvatinib but is still used, and whether it retains a niche in patients who cannot tolerate lenvatinib is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00984282","url":"https://clinicaltrials.gov/study/NCT00984282"},{"label":"Lancet 2014","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60421-9/fulltext"}],"tags":[],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00984282","phase":"3","setting":"Radioiodine-refractory differentiated thyroid cancer: sorafenib vs placebo","sponsor":"Bayer","result":"PFS 10.8 vs 5.8 months; HR 0.59.","yearReported":2013,"enrolled":417,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Sorafenib","value":10.8},{"name":"Placebo","value":5.8}],"hr":0.59,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60421-9/fulltext"}],"replication":"SELECT confirmed the class effect with a larger benefit.","route":"/trials/decision-sorafenib/"}
{"id":"eclipse-psma","kind":"trial","name":"ECLIPSE","aka":[],"tldr":"Curium's PSMA radioligand met its progression endpoint; survival data and an FDA filing are pending.","summary":"ECLIPSE, trial NCT05204927 sponsored by Curium and reported in 2025, tested 177Lu-PSMA-I&T given as six cycles of 7.4 GBq against a switch of androgen receptor pathway inhibitor in PSMA-positive, taxane-naive metastatic castration-resistant prostate cancer after one such inhibitor. It enrolled 439 men and met its primary radiographic progression-free survival endpoint according to the sponsor, with medians pending publication, overall survival maturing, study completion projected for 2029 and an FDA submission plan under discussion. Nuclide links it to prostate cancer and to the 177Lu-PSMA-I&T drug record; its result is consistent with PSMAfore for the pre-chemotherapy setting and contrasts with SPLASH, which used the same ligand but showed an unfavourable interim survival signal. Whether the survival data will support approval of a second lutetium PSMA agent is the open question.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT05204927","url":"https://clinicaltrials.gov/study/NCT05204927"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["lu177-psma-it"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05204927","phase":"3","setting":"PSMA-positive mCRPC after ARPI, taxane-naive: 177Lu-PSMA-I&T (7.4 GBq × 6) vs ARPI switch","sponsor":"Curium","result":"rPFS significantly improved.","yearReported":2025,"enrolled":439,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-I&T","note":"Met per sponsor; medians pending publication"},{"name":"ARPI switch"}],"source":"https://clinicaltrials.gov/study/NCT05204927"}],"replication":"Consistent with PSMAfore for the pre-chemotherapy setting; OS pending.","route":"/trials/eclipse-psma/"}
{"id":"embark","kind":"trial","name":"EMBARK","aka":[],"tldr":"Showed that treating a fast-rising PSA after surgery or radiation with enzalutamide delays spread.","summary":"EMBARK, trial NCT02319837 sponsored by Pfizer and Astellas and reported in 2023, showed that treating a fast-rising PSA after surgery or radiotherapy with enzalutamide delays the appearance of metastases. It randomised 1,068 men with high-risk biochemical recurrence, defined by a PSA doubling time of nine months or less, to enzalutamide plus leuprolide, enzalutamide alone or leuprolide alone, suspending treatment if the PSA became undetectable at 36 weeks, and met its primary metastasis-free survival endpoint for the combination; approval followed in November 2023 and a survival benefit for the combination was reported in 2025. Nuclide links it to prostate cancer, enzalutamide and the biochemical recurrence term. Whether treating a rising PSA early beats waiting for imaging-detected disease, now that PSMA PET finds it sooner, is the open question.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02319837","url":"https://clinicaltrials.gov/study/NCT02319837"}],"tags":[],"related":[],"indications":["prostate","prostate-bcr"],"sections":[],"technologies":[],"targets":[],"drugs":["enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02319837","phase":"3","setting":"High-risk biochemical recurrence (PSA doubling time ≤9 months) after local therapy: enzalutamide + leuprolide, enzalutamide alone, or leuprolide alone","sponsor":"Pfizer / Astellas","result":"MFS HR 0.42 (combination).","yearReported":2023,"enrolled":1068,"enrolledBasis":"registry","outcomes":[{"endpoint":"Metastasis-free survival, enzalutamide + leuprolide vs leuprolide","primary":true,"unit":"%","arms":[{"name":"Enzalutamide + leuprolide, 5-year MFS","n":355,"value":87.3},{"name":"Leuprolide alone, 5-year MFS","n":358,"value":71.4}],"hr":0.42,"ci":[0.3,0.61],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2303974"}],"replication":"Single pivotal trial in high-risk biochemical recurrence; OS immature.","route":"/trials/embark/"}
{"id":"estimabl2","kind":"trial","name":"ESTIMABL2","aka":[],"tldr":"Proved that most people with small, low-risk thyroid cancers can skip radioactive iodine after surgery without any increase in recurrence.","summary":"ESTIMABL2, trial NCT01837745 sponsored by Gustave Roussy and the French Endocrine Tumour Group and reported in 2022, proved that most people with small, low-risk differentiated thyroid cancers can skip radioactive iodine after total thyroidectomy without any increase in recurrence. It randomised 776 patients with pT1a to T1b, node-negative tumours to no radioiodine or 1.1 GBq ablation and met its non-inferiority endpoint on event-free status at three years, confirmed at five years in 2024. Nuclide links it to thyroid cancer, radioiodine therapy, radioactive iodine, the low-risk thyroid cancer term, Gustave Roussy and Martin Schlumberger, and together with IoN and HiLo it removed radioiodine from routine low-risk care in ATA and ESMO guidance; the UK IoN trial reached the same conclusion. Whether the same holds for larger low-risk tumours, as IoN suggested for pT2, is the remaining question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01837745","url":"https://clinicaltrials.gov/study/NCT01837745"},{"label":"NEJM 2022","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111953"},{"label":"5-year follow-up","url":"https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00276-6/fulltext"}],"tags":[],"related":[],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01837745","phase":"3","setting":"Low-risk differentiated thyroid cancer (pT1a-T1b N0/Nx) after total thyroidectomy: no radioiodine vs 1.1 GBq ablation","sponsor":"Gustave Roussy / French Endocrine Tumour Group","result":"3-year event-free 95.6% vs 95.9% (non-inferior).","yearReported":2022,"enrolled":776,"enrolledBasis":"registry","outcomes":[{"endpoint":"Patients without events at 3 years","primary":true,"unit":"%","arms":[{"name":"No radioiodine","value":95.6},{"name":"Radioiodine 1.1 GBq","value":95.9}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111953"}],"replication":"IoN (UK, Lancet 2025) reached the same conclusion in a pooled analysis.","route":"/trials/estimabl2/"}
{"id":"hd21","kind":"trial","name":"GHSG HD21","aka":[],"tldr":"A new brentuximab-based intensive regimen matched Europe's most effective (and most toxic) chemotherapy with far fewer side effects.","summary":"GHSG HD21, trial NCT02661503 sponsored by the German Hodgkin Study Group and published in the Lancet in 2024, showed that a new brentuximab-based intensive regimen, BrECADD, matched and then beat escalated BEACOPP, Europe's most effective and most toxic chemotherapy for advanced Hodgkin lymphoma, with far fewer side effects. It randomised about 1,500 patients aged 18 to 60 to PET-guided BrECADD or escalated BEACOPP for four to six cycles, met non-inferiority and then superiority on progression-free survival at four and five years, and reduced treatment-related morbidity while preserving fertility markers. Nuclide links it to Hodgkin lymphoma, PET-adapted therapy, brentuximab vedotin, Peter Borchmann, the German Hodgkin Study Group and the ECHELON-1 and S1826 papers. Whether an intensive regimen is still needed when nivolumab-AVD has performed so well is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02661503","url":"https://clinicaltrials.gov/study/NCT02661503"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-adapted-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02661503","phase":"3","setting":"Untreated advanced-stage classical Hodgkin lymphoma, age 18-60: PET-guided BrECADD vs escalated BEACOPP","sponsor":"German Hodgkin Study Group","result":"4-year PFS 94.3% vs 90.9%, HR 0.66; less toxicity.","yearReported":2024,"enrolled":1500,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 4 years","primary":true,"unit":"%","arms":[{"name":"BrECADD","n":742,"value":94.3},{"name":"eBEACOPP","n":740,"value":90.9}],"hr":0.66,"ci":[0.45,0.97],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/fulltext"},{"endpoint":"Treatment-related morbidity","unit":"%","arms":[{"name":"BrECADD","value":42},{"name":"eBEACOPP","value":59}],"source":"https://doi.org/10.1016/S0140-6736(24)01315-1"}],"route":"/trials/hd21/"}
{"id":"hilo","kind":"trial","name":"HiLo","aka":[],"tldr":"Showed a third of the usual radioactive iodine dose ablates the thyroid remnant just as well, with fewer side effects and less time in isolation.","summary":"HiLo, trial NCT00415233 sponsored by Cancer Research UK and reported in 2012, showed that a third of the usual radioactive iodine dose ablates the thyroid remnant just as well as the high dose in differentiated thyroid cancer, with fewer side effects and less time in isolation. It randomised 438 patients needing ablation to 1.1 GBq or 3.7 GBq of radioiodine, with recombinant TSH or thyroid hormone withdrawal, and met its non-inferiority endpoint on successful ablation, while recombinant TSH avoided hypothyroid symptoms. Nuclide links it to thyroid cancer, radioiodine therapy, radioactive iodine and Cancer Research UK, and the French ESTIMABL1 trial replicated low-dose non-inferiority at the same time. Low-dose ablation became standard for intermediate-risk disease and the trial paved the way to omitting ablation altogether in low-risk disease, as ESTIMABL2 and IoN then showed.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00415233","url":"https://clinicaltrials.gov/study/NCT00415233"},{"label":"NEJM 2012","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1109589"}],"tags":[],"related":[],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00415233","phase":"3","setting":"Differentiated thyroid cancer needing ablation: low-dose (1.1 GBq) vs high-dose (3.7 GBq) radioiodine, with recombinant TSH or thyroid hormone withdrawal","sponsor":"Cancer Research UK","result":"Ablation success 85.0% (1.1 GBq) vs 88.9% (3.7 GBq), non-inferior.","yearReported":2012,"enrolled":438,"enrolledBasis":"registry","outcomes":[{"endpoint":"Successful ablation","primary":true,"unit":"%","arms":[{"name":"1.1 GBq","value":85},{"name":"3.7 GBq","value":88.9}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1109589"}],"replication":"ESTIMABL1 (France) replicated low-dose non-inferiority simultaneously.","route":"/trials/hilo/"}
{"id":"ielsg37","kind":"trial","name":"IELSG37","aka":[],"tldr":"IELSG37 showed that people with primary mediastinal B-cell lymphoma whose scan is clear after chemotherapy do not need radiotherapy to the chest, sparing young patients decades of heart and breast cancer risk.","summary":"IELSG37 registered 545 patients with primary mediastinal large B-cell lymphoma treated with rituximab-containing immunochemotherapy (mostly R-CHOP or dose-adjusted EPOCH-R, by centre) and randomised the 268 who reached a complete metabolic response on end-of-treatment PET (Deauville 1 to 3) to 30 Gy consolidation radiotherapy or to observation.\n\nProgression-free survival at 30 months was 96.7 percent without radiotherapy and 98.5 percent with it, within the non-inferiority margin, with no difference in overall survival. Patients with residual PET uptake were not randomised and received radiotherapy, in whom outcomes were also good.\n\nThe trial settled a forty-year argument: mediastinal radiotherapy can be omitted in the majority of patients who reach complete metabolic response, and PET now decides who is irradiated.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT01599559","url":"https://clinicaltrials.gov/study/NCT01599559"},{"label":"Journal of Clinical Oncology 2024","url":"https://doi.org/10.1200/JCO.24.01373"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["fdg-pet","pet-adapted-therapy"],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01599559","phase":"3","setting":"Primary mediastinal large B-cell lymphoma in complete metabolic response on PET after rituximab-based immunochemotherapy: consolidation mediastinal radiotherapy versus observation","sponsor":"International Extranodal Lymphoma Study Group","result":"30-month progression-free survival 96.7% (observation) vs 98.5% (radiotherapy) in patients with complete metabolic response; radiotherapy can be omitted.","yearReported":2024,"enrolled":545,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 30 months","primary":true,"unit":"%","arms":[{"name":"Observation","n":132,"value":96.7},{"name":"Consolidation radiotherapy 30 Gy","n":136,"value":98.5}],"source":"https://doi.org/10.1200/JCO.24.01373"}],"replication":"Consistent with the single-arm National Cancer Institute DA-EPOCH-R series, in which no patient received radiotherapy and event-free survival was 93 percent.","route":"/trials/ielsg37/"}
{"id":"ion-trial","kind":"trial","name":"IoN","aka":[],"tldr":"The UK trial confirming that low-risk thyroid cancer patients can safely avoid radioactive iodine, published in 2025.","summary":"IoN, trial NCT01398085 sponsored by Cancer Research UK and UCL and published in the Lancet in 2025, is the UK trial confirming that low-risk differentiated thyroid cancer patients can safely avoid radioactive iodine after thyroidectomy. It randomised 504 patients with pT1 to T2, node-negative tumours without adverse features to no radioiodine or radioiodine ablation and met its non-inferiority endpoint on recurrence-free status at five years, extending the ESTIMABL2 finding to pT2 tumours. Nuclide links it to thyroid cancer, radioiodine therapy, radioactive iodine, the low-risk thyroid cancer term and Cancer Research UK, and it replicates ESTIMABL2. Guideline bodies now recommend against routine ablation in this group, and whether patients and clinicians accept doing less is the practical question that remains.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01398085","url":"https://clinicaltrials.gov/study/NCT01398085"},{"label":"Lancet 2025","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00629-4/fulltext"}],"tags":[],"related":[],"indications":["thyroid"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01398085","phase":"2/3","setting":"Low-risk differentiated thyroid cancer (pT1-T2, N0/Nx, no adverse features) after thyroidectomy: no radioiodine vs radioiodine ablation","sponsor":"Cancer Research UK / UCL","result":"5-year recurrence-free ~98% (no RAI) vs ~96% (RAI).","yearReported":2025,"enrolled":504,"enrolledBasis":"registry","outcomes":[{"endpoint":"Recurrence-free at 5 years","primary":true,"unit":"%","arms":[{"name":"No radioiodine","value":98},{"name":"Radioiodine","value":96}],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00629-4/fulltext"}],"replication":"Replicates ESTIMABL2.","route":"/trials/ion-trial/"}
{"id":"mcrpc","kind":"trial","name":"A Study of Pasritamig With or Without JNJ-87189401 Versus Placebo for Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC)","aka":[],"tldr":"A phase 3 trial testing JNJ-87189401 in prostate cancer, now recruiting.","summary":"A Study of Pasritamig With or Without JNJ-87189401 Versus Placebo for Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) is a phase 3 interventional study registered as NCT07164443, led by Janssen Research & Development, and recruiting on the registry. Official title: A Phase 3 Randomised, Double-blind, Placebo-controlled Study of Pasritamig (JNJ-78278343), a T Cell Engaging Agent Targeting Human Kallikrein 2, With or Without JNJ-87189401, a PSMA-CD28 Costimulatory Agent, Plus Best Supportive Care Versus Best Supportive Care for Late-line Metastatic Castration-resistant Prostate Cancer. Planned enrolment is 1203 participants (estimated). The study started in 2025-09-02 and primary completion is expected in 2028-08-18. No results have been posted on ClinicalTrials.gov.","status":"recruiting","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov NCT07164443","url":"https://clinicaltrials.gov/study/NCT07164443"}],"tags":["ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["jnj-87189401"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07164443","phase":"3","setting":"A Phase 3 Randomized, Double-blind, Placebo-controlled Study of Pasritamig (JNJ-78278343), a T Cell Engaging Agent Targeting Human Kallikrein 2, With or Without JNJ-87189401, a PSMA-CD28 Costimulatory Agent, Plus Best Supportive Care Versus Best Supportive Care for Late-line Metastatic Castration-resistant Prostate Cancer","sponsor":"Janssen Research & Development","enrolled":1203,"enrolledBasis":"registry","outcomes":[],"route":"/trials/mcrpc/"}
{"id":"nct02665065","kind":"trial","name":"Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia","aka":["SIERRA"],"tldr":"A phase 3 trial of Iomab-B run by Actinium Pharmaceuticals, active.","summary":"Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia is a phase 3 interventional study registered as NCT02665065 by Actinium Pharmaceuticals, with 153 participants enrolled, started 2016-06. Conditions listed: Acute Myeloid Leukemia, Leukemia, Acute Myeloid, Myeloid Leukemia, Acute, Leukemia, Myeloid, Acute. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT02665065","url":"https://clinicaltrials.gov/study/NCT02665065"}],"tags":["ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["iomab-b"],"companies":["actinium-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02665065","phase":"3","setting":"A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)","sponsor":"Actinium Pharmaceuticals","enrolled":153,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct02665065/"}
{"id":"nct02952508","kind":"trial","name":"Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom","aka":["CLOVER-1"],"tldr":"A phase 2 trial of Iopofosine I 131 single dose in waldenström macroglobulinaemia, multiple myeloma, chronic lymphocytic leukaemia, non-Hodgkin lymphoma, mantle cell lymphoma and diffuse large B-cell lymphoma, run by Cellectar Biosciences, Inc., active and no longer recruiting.","summary":"Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom is a phase 2 interventional study registered as NCT02952508 by Cellectar Biosciences, Inc., with 120 participants enrolled, started 2017-07-26 and due to reach its primary completion in 2026-06-22. Interventions recorded: Iopofosine I 131 single dose, Iopofosine I 131 multiple dose and Iopofosine I 131 fractionated dose.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT02952508","url":"https://clinicaltrials.gov/study/NCT02952508"}],"tags":["pipeline","ctgov-ingest"],"related":["i-131"],"indications":["dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["cellectar"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02952508","phase":"2","setting":"An Open-Label, Multicenter, Phase 2 Study of Iopofosine I 131 (CLR 131) in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1) and Expansion Cohort in Patients With Waldenstrom Macroglobulinemia (CLOVER-WaM)","sponsor":"Cellectar Biosciences, Inc.","enrolled":120,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct02952508/"}
{"id":"nct03444844","kind":"trial","name":"Biodistribution and Dosimetry of Ga-68 P16-093 in Prostate Cancer","aka":[],"tldr":"A phase 1/2 trial of Ga-68 P16-093 PET/CT scan in prostate cancer, run by Five Eleven Pharma, Inc., active and no longer recruiting.","summary":"Biodistribution and Dosimetry of Ga-68 P16-093 in Prostate Cancer is a phase 1/2 interventional study registered as NCT03444844 by Five Eleven Pharma, Inc., with 60 participants enrolled, started 2018-05-10 and due to reach its primary completion in 2020-10-27. Interventions recorded: Ga-68 P16-093 PET/CT scan.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT03444844","url":"https://clinicaltrials.gov/study/NCT03444844"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68"],"indications":["prostate","prostate-bcr"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03444844","phase":"1/2","setting":"Biodistribution and Dosimetry of Ga-68 P16-093 in Prostate Cancer Patients With Intermediate/High Risk Primary Disease or Biochemical Recurrence After Treatment","sponsor":"Five Eleven Pharma, Inc.","enrolled":60,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03444844/"}
{"id":"nct03533283","kind":"trial","name":"An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma","aka":[],"tldr":"A phase 1/2 trial of Glofitamab, Atezolizumab, Obinutuzumab, Tocilizumab and Polatuzumab vedotin in hodgkin lymphoma, run by Hoffmann-La Roche, active and no longer recruiting.","summary":"An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma is a phase 1/2 interventional study registered as NCT03533283 by Hoffmann-La Roche, with 211 participants enrolled, started 2018-05-08 and due to reach its primary completion in 2026-10-16. Interventions recorded: Glofitamab, Atezolizumab, Obinutuzumab, Tocilizumab, Polatuzumab Vedotin and 89Zr-Df-IAB22M2C.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT03533283","url":"https://clinicaltrials.gov/study/NCT03533283"}],"tags":["pipeline","ctgov-ingest"],"related":["zr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03533283","phase":"1/2","setting":"An Open-Label, Multi-Center, Phase IB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin (Plus a Single Pre-Treatment Dose of Obinutuzumab) in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma","sponsor":"Hoffmann-La Roche","enrolled":211,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03533283/"}
{"id":"nct03690388","kind":"trial","name":"A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Va","aka":[],"tldr":"A phase 3 trial of Cabozantinib in thyroid cancer, run by Exelixis, active and no longer recruiting.","summary":"A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy is a phase 3 interventional study registered as NCT03690388 by Exelixis, with 187 participants enrolled, started 2018-10-05 and due to reach its primary completion in 2020-08-19. Interventions recorded: Cabozantinib, Placebo. Conditions listed: Differentiated Thyroid Cancer. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT03690388","url":"https://clinicaltrials.gov/study/NCT03690388"}],"tags":["ctgov-ingest"],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03690388","phase":"3","setting":"A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy","sponsor":"Exelixis","enrolled":187,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03690388/"}
{"id":"nct03972488","kind":"trial","name":"Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET","aka":["NETTER-2"],"tldr":"A phase 3 trial of Lutetium-177 dotatate in pancreatic ductal adenocarcinoma, run by Advanced Accelerator Applications, active and no longer recruiting.","summary":"Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET is a phase 3 interventional study registered as NCT03972488 by Advanced Accelerator Applications, with 226 participants enrolled, started 2020-01-08 and due to reach its primary completion in 2023-07-20. Interventions recorded: Lutathera, 30 mg Octreotide long acting repeatable (LAR) (Sandostatin LAR Depot), 2.5% Lys-Arg sterile amino acid solution and High dose 60 mg octreotide long-acting repeatable. Results have been posted on the registry.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT03972488","url":"https://clinicaltrials.gov/study/NCT03972488"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["neuroendocrine","small-intestinal-net","pancreatic-net","grade-3-net"],"sections":[],"technologies":[],"targets":[],"drugs":["lutathera"],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03972488","phase":"3","setting":"A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET","sponsor":"Advanced Accelerator Applications","enrolled":226,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03972488/"}
{"id":"nct03972657","kind":"trial","name":"A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metasta","aka":[],"tldr":"A phase 1/2 trial of Cemiplimab in prostate cancer and renal cell carcinoma, run by Regeneron Pharmaceuticals, now recruiting.","summary":"A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors is a phase 1/2 interventional study registered as NCT03972657 by Regeneron Pharmaceuticals, with 345 participants planned, started 2019-08-12 and due to reach its primary completion in 2027-11-15. Interventions recorded: REGN5678, Cemiplimab. Conditions listed: Metastatic Castration-Resistant Prostate Cancer (mCRPC), Clear Cell Renal Cell Carcinoma (ccRCC). No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT03972657","url":"https://clinicaltrials.gov/study/NCT03972657"}],"tags":["ctgov-ingest"],"related":[],"indications":["prostate","rcc","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03972657","phase":"1/2","setting":"A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression","sponsor":"Regeneron Pharmaceuticals","enrolled":345,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03972657/"}
{"id":"nct04557059","kind":"trial","name":"A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer","aka":["PRIMORDIUM"],"tldr":"A phase 3 trial of Apalutamide in prostate cancer, run by Janssen Pharmaceutica N.V., Belgium, active and no longer recruiting.","summary":"A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer is a phase 3 interventional study registered as NCT04557059 by Janssen Pharmaceutica N.V., Belgium, with 691 participants enrolled, started 2020-11-12 and due to reach its primary completion in 2029-08-27. Interventions recorded: Radiotherapy, LHRHa and Apalutamide.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04557059","url":"https://clinicaltrials.gov/study/NCT04557059"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04557059","phase":"3","setting":"A Randomized, Controlled, Multicenter, Open-label Study to Investigate the Efficacy and Safety of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer, Assessed by PSMA-PET With an Observational Cohort","sponsor":"Janssen Pharmaceutica N.V., Belgium","enrolled":691,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04557059/"}
{"id":"nct04711135","kind":"trial","name":"Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs","aka":["NETTER-P"],"tldr":"A phase 2 trial of Lutetium-177 dotatate in pheochromocytoma and paraganglioma, run by Advanced Accelerator Applications, active and no longer recruiting.","summary":"Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs is a phase 2 interventional study registered as NCT04711135 by Advanced Accelerator Applications, with 11 participants enrolled, started 2022-08-31 and due to reach its primary completion in 2024-03-12. Interventions recorded: Lutetium [177Lu] oxodotreotide/dotatate. Conditions listed: Gastroenteropancreatic Neuroendocrine Tumors, Pheochromocytoma, Paraganglioma. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04711135","url":"https://clinicaltrials.gov/study/NCT04711135"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["pheochromocytoma-paraganglioma"],"sections":[],"technologies":[],"targets":[],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04711135","phase":"2","setting":"A Multicenter Open-label Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine (GEP-NET) Tumors, Pheochromocytoma and Paragangliomas (PPGL)","sponsor":"Advanced Accelerator Applications","enrolled":11,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04711135/"}
{"id":"nct04724369","kind":"trial","name":"Open-Label Study of 18F-mFBG for Imaging Neuroblastoma","aka":[],"tldr":"A phase 3 trial of 18F-MFBG in neuroblastoma, run by Innervate Radiopharmaceuticals LLC (Formerly: Illumina Radiopharmaceuticals LLC), active and no longer recruiting.","summary":"Open-Label Study of 18F-mFBG for Imaging Neuroblastoma is a phase 3 interventional study registered as NCT04724369 by Innervate Radiopharmaceuticals LLC (Formerly: Illumina Radiopharmaceuticals LLC), with 43 participants enrolled, started 2021-11-18 and due to reach its primary completion in 2026-07-30. Interventions recorded: 18F-MFBG.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04724369","url":"https://clinicaltrials.gov/study/NCT04724369"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":["neuroblastoma"],"sections":[],"technologies":["pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04724369","phase":"3","setting":"A Prospective Phase 3 Multi-center Study to Assess the Efficacy and Safety of 18F-mFBG PET Imaging in Subjects With Neuroblastoma","sponsor":"Innervate Radiopharmaceuticals LLC (Formerly: Illumina Radiopharmaceuticals LLC)","enrolled":43,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04724369/"}
{"id":"nct04807257","kind":"trial","name":"Auger Molecular Therapy (AMT) for Malignant Cutaneous Lesions Treatment","aka":[],"tldr":"A phase 1/2 trial of Auger Molecular Therapy (AMT) in advanced solid tumours, run by NanoRay Biotech Co., Ltd., now recruiting.","summary":"Auger Molecular Therapy (AMT) for Malignant Cutaneous Lesions Treatment is a phase 1/2 interventional study registered as NCT04807257 by NanoRay Biotech Co., Ltd., with 18 participants planned, started 2024-08-05 and due to reach its primary completion in 2025-12-31. Interventions recorded: Auger Molecular Therapy (AMT).","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04807257","url":"https://clinicaltrials.gov/study/NCT04807257"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04807257","phase":"1/2","setting":"A First-in-Human Study of Auger Molecular Therapy (AMT) in Patients With Malignant Cutaneous Lesions From Advanced Solid Tumors","sponsor":"NanoRay Biotech Co., Ltd.","enrolled":18,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04807257/"}
{"id":"nct04868604","kind":"trial","name":"64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)","aka":["SECuRE"],"tldr":"A phase 1/2 trial of 64Cu-SAR-bisPSMA in prostate cancer, run by Clarity Pharmaceuticals Ltd, now recruiting.","summary":"64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE) is a phase 1/2 interventional study registered as NCT04868604 by Clarity Pharmaceuticals Ltd, with 54 participants planned, started 2021-08-11 and due to reach its primary completion in 2026-09. Interventions recorded: 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04868604","url":"https://clinicaltrials.gov/study/NCT04868604"}],"tags":["pipeline","ctgov-ingest"],"related":["cu-64","cu-67"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["clarity-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04868604","phase":"1/2","setting":"A Phase I/IIa Theranostic Study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer","sponsor":"Clarity Pharmaceuticals Ltd","enrolled":54,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04868604/"}
{"id":"nct04919226","kind":"trial","name":"Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE","aka":["COMPOSE"],"tldr":"A phase 3 trial of 177Lu-edotreotide, Temozolomide, Capecitabine, Everolimus, Leucovorin (folinic acid) and Oxaliplatin in neuroendocrine tumours, run by ITM Solucin GmbH, active and no longer recruiting.","summary":"Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE is a phase 3 interventional study registered as NCT04919226 by ITM Solucin GmbH, with 259 participants enrolled, started 2021-12-21 and due to reach its primary completion in 2027-06. Interventions recorded: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT, CAPTEM (Capecitabine and Temozolomide), Everolimus and FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin).","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04919226","url":"https://clinicaltrials.gov/study/NCT04919226"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["neuroendocrine","grade-3-net","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["itm-11","temozolomide","capecitabine","everolimus"],"companies":["itm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04919226","phase":"3","setting":"A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin","sponsor":"ITM Solucin GmbH","enrolled":259,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04919226/"}
{"id":"nct04939610","kind":"trial","name":"A Study of 177Lu-FAP-2286 in Advanced Solid Tumors","aka":["LuMIERE"],"tldr":"A phase 1/2 trial of FAP-2286 (177Lu / 68Ga) in advanced solid tumours, run by Novartis Pharmaceuticals, now recruiting.","summary":"A Study of 177Lu-FAP-2286 in Advanced Solid Tumors is a phase 1/2 interventional study registered as NCT04939610 by Novartis Pharmaceuticals, with 222 participants planned, started 2021-07-30 and due to reach its primary completion in 2027-12-31. Interventions recorded: 68Ga-FAP-2286 and 177Lu-FAP-2286.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT04939610","url":"https://clinicaltrials.gov/study/NCT04939610"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286"],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04939610","phase":"1/2","setting":"LuMIERE: A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FAP-2286 in Patients With an Advanced Solid Tumor","sponsor":"Novartis Pharmaceuticals","enrolled":222,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct04939610/"}
{"id":"nct05004285","kind":"trial","name":"Evaluate the Clinical Usefulness of [F-18]Florastamin PET/CT Imaging Diagnosis Compared to MRI Diagnosis","aka":[],"tldr":"A phase 3 trial of Florastamin F-18 run by FutureChem, active.","summary":"Evaluate the Clinical Usefulness of [F-18]Florastamin PET/CT Imaging Diagnosis Compared to MRI Diagnosis is a phase 3 interventional study registered as NCT05004285 by FutureChem, with 398 participants planned, started 2021-04-28. Conditions listed: High Risk Prostate Carcinoma. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05004285","url":"https://clinicaltrials.gov/study/NCT05004285"}],"tags":["ctgov-ingest"],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["florastamin-f18"],"companies":["futurechem"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05004285","phase":"3","setting":"A Multi Center, Non-randomized, Open, Phase 3 Study to Evaluate the Clinical Usefulness of [F-18]Florastamin PET/CT Imaging Diagnosis Compared to MRI Diagnosis in Prostate Cancer Risk Groups","sponsor":"FutureChem","enrolled":398,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05004285/"}
{"id":"nct05063565","kind":"trial","name":"TheraSphere With Durvalumab and Tremelimumab for HCC","aka":["ROWAN"],"tldr":"A phase 2 trial of Durvalumab in hepatocellular carcinoma, run by Boston Scientific Corporation, active and no longer recruiting.","summary":"TheraSphere With Durvalumab and Tremelimumab for HCC is a phase 2 interventional study registered as NCT05063565 by Boston Scientific Corporation, with 100 participants planned, started 2023-11-03 and due to reach its primary completion in 2027-06. Interventions recorded: TheraSphere Y-90 glass microsphere therapy, Durvalumab (Imfinzi) immunotherapy, Tremelimumab immunotherapy. Conditions listed: Hepatocellular Carcinoma. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05063565","url":"https://clinicaltrials.gov/study/NCT05063565"}],"tags":["ctgov-ingest"],"related":["y-90"],"indications":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":["durvalumab"],"companies":["boston-scientific"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05063565","phase":"2","setting":"An Open-Label, Prospective, Multi-Center Clinical Trial to Evaluate the Efficacy and Safety of TheraSphere™ Followed by Durvalumab (Imfinzi®) With Tremelimumab (Imjudo®) for Hepatocellular Carcinoma (HCC)","sponsor":"Boston Scientific Corporation","enrolled":100,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05063565/"}
{"id":"nct05142696","kind":"trial","name":"A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab","aka":[],"tldr":"A phase 1/2 trial of Lutetium-177 dotatate, FAP-2286, Atezolizumab in small-cell lung cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab is a phase 1/2 interventional study registered as NCT05142696 by Novartis Pharmaceuticals, with 55 participants enrolled, started 2022-07-13 and due to reach its primary completion in 2028-03-07. Interventions recorded: [177Lu]Lu-DOTA-TATE, Atezolizumab, [68Ga]Ga-DOTA-TATE, Carboplatin, Etoposide. Conditions listed: Extensive Stage Small Cell Lung Cancer. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05142696","url":"https://clinicaltrials.gov/study/NCT05142696"}],"tags":["ctgov-ingest"],"related":["ga-68","lu-177"],"indications":["sclc"],"sections":[],"technologies":[],"targets":[],"drugs":["lutathera","fap-2286"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05142696","phase":"1/2","setting":"A Phase Ib/II Dose Finding Study Assessing Safety and Efficacy of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) in Combination With Carboplatin, Etoposide, and Atezolizumab in Induction and With Atezolizumab in Maintenance Phase","sponsor":"Novartis Pharmaceuticals","enrolled":55,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05142696/"}
{"id":"nct05219500","kind":"trial","name":"Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST).","aka":["TATCIST"],"tldr":"A phase 2 trial of FPI-2265 in prostate cancer, run by Fusion Pharmaceuticals Inc., active and no longer recruiting.","summary":"Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST). is a phase 2 interventional study registered as NCT05219500 by Fusion Pharmaceuticals Inc., with 115 participants planned, started 2021-12-16 and due to reach its primary completion in 2025-05-30. Interventions recorded: FPI-2265. Conditions listed: Metastatic Castration Resistant Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05219500","url":"https://clinicaltrials.gov/study/NCT05219500"}],"tags":["ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fpi-2265"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05219500","phase":"2","setting":"PSMA-directed Targeted Alpha Therapy With FPI-2265 (225Ac-PSMA-I&T) for the Treatment of Metastatic Castration-resISTant Prostate Cancer (TATCIST). A Phase II Clinical Trial.","sponsor":"Fusion Pharmaceuticals Inc.","enrolled":115,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05219500/"}
{"id":"nct05381103","kind":"trial","name":"PSMA-PET to Guide Prostatectomy","aka":[],"tldr":"A phase 2/3 trial of an investigational treatment in prostate cancer, run by Five Eleven Pharma, Inc., now recruiting.","summary":"PSMA-PET to Guide Prostatectomy is a phase 2/3 interventional study registered as NCT05381103 by Five Eleven Pharma, Inc., with 288 participants planned, started 2021-10-01 and due to reach its primary completion in 2028-06-01.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05381103","url":"https://clinicaltrials.gov/study/NCT05381103"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate"],"sections":[],"technologies":["pet"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05381103","phase":"2/3","setting":"PSMA-PET to Guide Prostatectomy: A Randomized Trial","sponsor":"Five Eleven Pharma, Inc.","enrolled":288,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05381103/"}
{"id":"nct05413850","kind":"trial","name":"Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection","aka":[],"tldr":"A phase 1/2 trial of FAP-2286 in prostate cancer, run by Blue Earth Therapeutics Ltd, now recruiting.","summary":"Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection is a phase 1/2 interventional study registered as NCT05413850 by Blue Earth Therapeutics Ltd, with 82 participants planned, started 2022-07-20 and due to reach its primary completion in 2026-08-27. Interventions recorded: Lutetium (177Lu) rhPSMA-10.1 Injection, 18F-rhPSMA-7.3 injection (in phase 1 only). Conditions listed: Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, mCRPC, Urogenital Neoplasms. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05413850","url":"https://clinicaltrials.gov/study/NCT05413850"}],"tags":["ctgov-ingest"],"related":["f-18","lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05413850","phase":"1/2","setting":"An Open-label, Multicentre, Integrated Phase 1 & 2 Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Anti-tumour Activity of Lutetium (177Lu) rhPSMA-10.1 Injection in Men With Metastatic Castrate-resistant Prostate Cancer","sponsor":"Blue Earth Therapeutics Ltd","enrolled":82,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05413850/"}
{"id":"nct05459844","kind":"trial","name":"A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs","aka":[],"tldr":"A phase 3 trial of Lutetium[177Lu] Oxodotreotide Injection in neuroendocrine tumours, run by Sinotau Pharmaceutical Group, active and no longer recruiting.","summary":"A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs is a phase 3 interventional study registered as NCT05459844 by Sinotau Pharmaceutical Group, with 196 participants enrolled, started 2022-08-31 and due to reach its primary completion in 2024-06-26. Interventions recorded: Lutetium[177Lu] Oxodotreotide Injection and Octreotide LAR.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05459844","url":"https://clinicaltrials.gov/study/NCT05459844"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["sinotau-pharmaceutical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05459844","phase":"3","setting":"A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With Inoperable, Progressive, Well Differentiated, Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine Tumours","sponsor":"Sinotau Pharmaceutical Group","enrolled":196,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05459844/"}
{"id":"nct05547061","kind":"trial","name":"A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy","aka":[],"tldr":"A phase 1/2 trial of Lu-177-DGUL in prostate cancer, run by Cellbion Co., Ltd., active and no longer recruiting.","summary":"A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy is a phase 1/2 interventional study registered as NCT05547061 by Cellbion Co., Ltd., with 91 participants enrolled, started 2021-04-12 and due to reach its primary completion in 2024-12-31. Interventions recorded: Lu-177-DGUL and Ga-68-NGUL.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05547061","url":"https://clinicaltrials.gov/study/NCT05547061"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68","lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05547061","phase":"1/2","setting":"A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy","sponsor":"Cellbion Co., Ltd.","enrolled":91,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05547061/"}
{"id":"nct05636618","kind":"trial","name":"Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors","aka":[],"tldr":"A phase 1/2 trial of [203Pb]VMT-α-NET in neuroendocrine tumours, pancreatic ductal adenocarcinoma and pheochromocytoma and paraganglioma, run by Perspective Therapeutics, now recruiting.","summary":"Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors is a phase 1/2 interventional study registered as NCT05636618 by Perspective Therapeutics, with 300 participants planned, started 2023-09-27 and due to reach its primary completion in 2029-11-26. Interventions recorded: [203Pb]VMT-α-NET and [212Pb]VMT-α-NET.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05636618","url":"https://clinicaltrials.gov/study/NCT05636618"}],"tags":["pipeline","ctgov-ingest"],"related":["pb-212"],"indications":["neuroendocrine","pheochromocytoma-paraganglioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["perspective-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05636618","phase":"1/2","setting":"A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors","sponsor":"Perspective Therapeutics","enrolled":300,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05636618/"}
{"id":"nct05655312","kind":"trial","name":"MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma","aka":[],"tldr":"A phase 1/2 trial of Nivolumab in melanoma, run by Perspective Therapeutics, now recruiting.","summary":"MC1R-targeted Alpha-particle Monotherapy and Combination Therapy Trial With Nivolumab in Adults With Advanced Melanoma is a phase 1/2 interventional study registered as NCT05655312 by Perspective Therapeutics, with 300 participants planned, started 2023-06-01 and due to reach its primary completion in 2027-12-31. Interventions recorded: [203Pb]VMT01, [212Pb]VMT01, Nivolumab. Conditions listed: Recurrent Melanoma (Skin), Metastatic Melanoma, Melanoma Stage IV, Melanoma Stage III. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05655312","url":"https://clinicaltrials.gov/study/NCT05655312"}],"tags":["ctgov-ingest"],"related":["pb-212"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["perspective-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05655312","phase":"1/2","setting":"A Phase I/IIa, First-In-Human, Multi-Center, Monotherapy and Combination-Therapy With Nivolumab, Dose-Finding and Dose-Expansion Study of [212Pb]VMT01 Melanocortin-1 Receptor-Targeted, Image-Guided Alpha-Particle Therapy in Subjects With Previously Treated Unresectable or Metastatic Melanoma","sponsor":"Perspective Therapeutics","enrolled":300,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05655312/"}
{"id":"nct05658003","kind":"trial","name":"A Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in Taxane Treatment Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer","aka":[],"tldr":"A phase 2 trial of [177Lu]Lu-PSMA-617 in prostate cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"A Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in Taxane Treatment Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer is a phase 2 interventional study registered as NCT05658003 by Novartis Pharmaceuticals, with 63 participants enrolled, started 2023-05-05 and due to reach its primary completion in 2024-12-02. Interventions recorded: [177Lu]Lu-PSMA-617, ARDT and [68Ga]Ga-PSMA-11.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05658003","url":"https://clinicaltrials.gov/study/NCT05658003"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68","lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05658003","phase":"2","setting":"An Open-label, Multi-center, Randomized, Phase II Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer","sponsor":"Novartis Pharmaceuticals","enrolled":63,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05658003/"}
{"id":"nct05682443","kind":"trial","name":"ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC","aka":["PRESERVE-006"],"tldr":"A phase 1/2 trial of Gotistobart, Lutetium-177 vipivotide tetraxetan in prostate cancer, run by OncoC4, Inc., active and no longer recruiting.","summary":"ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC is a phase 1/2 interventional study registered as NCT05682443 by OncoC4, Inc., with 148 participants enrolled, started 2023-12-11 and due to reach its primary completion in 2026-11-30. Interventions recorded: ONC-392 low, ONC-392 high, lutetium Lu 177 vipivotide tetraxetan. Conditions listed: Metastatic Castration-resistant Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05682443","url":"https://clinicaltrials.gov/study/NCT05682443"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05682443","phase":"1/2","setting":"Randomized Study of ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Progressed on Androgen Receptor (AR) Pathway Inhibition","sponsor":"OncoC4, Inc.","enrolled":148,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05682443/"}
{"id":"nct05706129","kind":"trial","name":"A Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of [68Ga]Ga-DPI-4452 in renal cell carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, bladder & urothelial cancer, head and neck squamous cell carcinoma and triple-negative breast cancer, run by Lumara Bio Oncologics GmbH, now recruiting.","summary":"A Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors is a phase 1/2 interventional study registered as NCT05706129 by Lumara Bio Oncologics GmbH, with 270 participants planned, started 2023-03-14 and due to reach its primary completion in 2027-06. Interventions recorded: [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05706129","url":"https://clinicaltrials.gov/study/NCT05706129"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68","lu-177"],"indications":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05706129","phase":"1/2","setting":"A Multicenter, Open-Label, Non-Randomized Phase 1/2 Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Patients With Unresectable Locally Advanced or Metastatic Solid Tumors","sponsor":"Lumara Bio Oncologics GmbH","enrolled":270,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05706129/"}
{"id":"nct05849298","kind":"trial","name":"A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC","aka":["PSMACare"],"tldr":"A phase 2 trial of AAA617 in prostate cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC is a phase 2 interventional study registered as NCT05849298 by Novartis Pharmaceuticals, with 49 participants enrolled, started 2024-01-03 and due to reach its primary completion in 2026-12-23. Interventions recorded: AAA617, AAA517, Piflufolastat F 18, ARPI and ADT.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05849298","url":"https://clinicaltrials.gov/study/NCT05849298"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05849298","phase":"2","setting":"An International Prospective Open-label, Multi-center, Randomized, Non-comparative Phase II Study of Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) Alone and Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) in Combination With Androgen Receptor Pathway Inhibitors in Patients With PSMA PET Scan Positive Castration-Resistant Prostate Cancer","sponsor":"Novartis Pharmaceuticals","enrolled":49,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05849298/"}
{"id":"nct05884255","kind":"trial","name":"An Open-label Phase 3 Study of Lutetium (177Lu) Oxodotreotide Injection in Subjects With Advanced Gastrointestinal Pancreatic Neuroendocrine Tumors.","aka":[],"tldr":"A phase 3 trial of Lutetium (177Lu) Oxodotreotide Injection；long-acting Octreotide in pancreatic ductal adenocarcinoma, run by Jiangsu HengRui Medicine Co., Ltd., now recruiting.","summary":"An Open-label Phase 3 Study of Lutetium (177Lu) Oxodotreotide Injection in Subjects With Advanced Gastrointestinal Pancreatic Neuroendocrine Tumors. is a phase 3 interventional study registered as NCT05884255 by Jiangsu HengRui Medicine Co., Ltd., with 220 participants planned, started 2023-07-06 and due to reach its primary completion in 2026-12. Interventions recorded: Lutetium (177Lu) Oxodotreotide Injection；long-acting Octreotide and long-acting Octreotide.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05884255","url":"https://clinicaltrials.gov/study/NCT05884255"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05884255","phase":"3","setting":"Randomized, Open, Positive Control Phase III Clinical Trial of Lutetium (177Lu) Oxodotreotide Injection Combined With Standard-dose Long-acting Octreotide Versus High-dose Long-acting Octreotide in the Treatment of Somatostatin Receptor-positive Advanced Gastrointestinal Pancreatic Neuroendocrine Tumors.","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","enrolled":220,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05884255/"}
{"id":"nct05936658","kind":"trial","name":"[18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer","aka":[],"tldr":"A phase 3 trial of Florastamin F-18 run by FutureChem, active.","summary":"[18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer is a phase 3 interventional study registered as NCT05936658 by FutureChem, with 138 participants enrolled, started 2023-05-08. Conditions listed: High Risk Prostate Carcinoma. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05936658","url":"https://clinicaltrials.gov/study/NCT05936658"}],"tags":["ctgov-ingest"],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["florastamin-f18"],"companies":["futurechem"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05936658","phase":"3","setting":"A Multi-center, Open-label, Single Arm Phase III Clinical Trial for the Diagnostic Efficacy Assessment and Safety Evaluation by [18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer","sponsor":"FutureChem","enrolled":138,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05936658/"}
{"id":"nct05939414","kind":"trial","name":"An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.","aka":[],"tldr":"A phase 3 trial of FAP-2286 in prostate cancer, run by Novartis Pharmaceuticals, now recruiting.","summary":"An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC. is a phase 3 interventional study registered as NCT05939414 by Novartis Pharmaceuticals, with 450 participants planned, started 2024-03-12 and due to reach its primary completion in 2028-04-25. Interventions recorded: AAA617, piflufolastat (18F), gallium (68Ga) gozetotide (25μg). Conditions listed: Oligometastatic Prostate Cancer (OMPC). No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT05939414","url":"https://clinicaltrials.gov/study/NCT05939414"}],"tags":["ctgov-ingest"],"related":["f-18","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05939414","phase":"3","setting":"An International, Prospective, Open-label, Multi-center, Randomized Phase III Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) Versus Observation to Delay Castration or Disease Recurrence in Adult Male Patients With Prostate-specific Membrane Antigen (PSMA) Positive Oligometastatic Prostate Cancer (OMPC)","sponsor":"Novartis Pharmaceuticals","enrolled":450,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct05939414/"}
{"id":"nct06004661","kind":"trial","name":"Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function","aka":[],"tldr":"A phase 2 trial of Lutetium-177 vipivotide tetraxetan in prostate cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function is a phase 2 interventional study registered as NCT06004661 by Novartis Pharmaceuticals, with 23 participants enrolled, started 2024-04-04 and due to reach its primary completion in 2026-12-14. Interventions recorded: AAA617, 68Ga-PSMA-11. Conditions listed: Metastatic Castration-Resistant Prostate Cancer (mCRPC). No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06004661","url":"https://clinicaltrials.gov/study/NCT06004661"}],"tags":["ctgov-ingest"],"related":["ga-68","lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06004661","phase":"2","setting":"An Open-label Dosimetry, Biodistribution, Tolerability and Safety Study of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Moderately and Severely Impaired and With Normal Renal Function.","sponsor":"Novartis Pharmaceuticals","enrolled":23,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06004661/"}
{"id":"nct06040099","kind":"trial","name":"A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepat","aka":["EMERALD-Y90"],"tldr":"A phase 2 trial of Durvalumab, Bevacizumab in hepatocellular carcinoma, run by AstraZeneca, active and no longer recruiting.","summary":"A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE is a phase 2 interventional study registered as NCT06040099 by AstraZeneca, with 58 participants enrolled, started 2024-02-13 and due to reach its primary completion in 2026-07-01. Interventions recorded: Durvalumab, Bevacizumab, Transarterial Radioembolization (TARE). Conditions listed: Hepatocellular Carcinoma (HCC). No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06040099","url":"https://clinicaltrials.gov/study/NCT06040099"}],"tags":["ctgov-ingest"],"related":["y-90"],"indications":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06040099","phase":"2","setting":"Phase II Single-Arm Study of Durvalumab and Bevacizumab Following Transarterial Radioembolization Using Yttrium-90 Glass Microspheres (TheraSphere™) in Unresectable Hepatocellular Carcinoma Amenable to Locoregional Therapy","sponsor":"AstraZeneca","enrolled":58,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06040099/"}
{"id":"nct06084806","kind":"trial","name":"Test-retest Evaluation of [18F]F-AraG PET","aka":[],"tldr":"A phase 2 trial of [18F]F-ARAG PET in non-small-cell lung cancer, run by CellSight Technologies, Inc., now recruiting.","summary":"Test-retest Evaluation of [18F]F-AraG PET is a phase 2 interventional study registered as NCT06084806 by CellSight Technologies, Inc., with 10 participants planned, started 2023-10-31 and due to reach its primary completion in 2025-10-31. Interventions recorded: [18F]F-ARAG PET.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06084806","url":"https://clinicaltrials.gov/study/NCT06084806"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06084806","phase":"2","setting":"Test-retest Evaluation of [18F]F-AraG PET in Non-small Cell Lung Cancer (NSCLC) Patients","sponsor":"CellSight Technologies, Inc.","enrolled":10,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06084806/"}
{"id":"nct06107374","kind":"trial","name":"Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG","aka":[],"tldr":"A phase 2 trial of [18F]F-AraG in non-small-cell lung cancer, run by CellSight Technologies, Inc., now recruiting.","summary":"Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG is a phase 2 interventional study registered as NCT06107374 by CellSight Technologies, Inc., with 20 participants planned, started 2023-11-01 and due to reach its primary completion in 2025-12-31. Interventions recorded: [18F]F-AraG.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06107374","url":"https://clinicaltrials.gov/study/NCT06107374"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06107374","phase":"2","setting":"Imaging of T-cell Activation With [18F]F-araG in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Undergoing PD-1/PD-L1 Directed Therapy","sponsor":"CellSight Technologies, Inc.","enrolled":20,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06107374/"}
{"id":"nct06122584","kind":"trial","name":"Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed Prostate Cancer","aka":[],"tldr":"A phase 3 trial of PSMA-1007 F-18 run by ABX advanced biochemical compounds GmbH in prostate cancer, now recruiting.","summary":"Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed Prostate Cancer is a phase 3 interventional study registered as NCT06122584 by ABX advanced biochemical compounds GmbH, with 380 participants planned, started 2024-06-13. Conditions listed: Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06122584","url":"https://clinicaltrials.gov/study/NCT06122584"}],"tags":["ctgov-ingest"],"related":["f-18"],"indications":["prostate","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["psma-1007-f18"],"companies":["abx-advanced-biochemical-compounds"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06122584","phase":"3","setting":"Prospective, Multi-Center Study to Assess the Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed High-Risk or Very-High-Risk Prostate Cancer","sponsor":"ABX advanced biochemical compounds GmbH","enrolled":380,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06122584/"}
{"id":"nct06139575","kind":"trial","name":"Phase 1/2 Clinical Study of Lutetium Lu 177 JH020002 Injection in Patients With Advanced Prostate Cancer","aka":[],"tldr":"A phase 1/2 trial of Lutetium Lu 177 JH020002 Injection in prostate cancer, run by Bivision Pharmaceuticals, Inc., now recruiting.","summary":"Phase 1/2 Clinical Study of Lutetium Lu 177 JH020002 Injection in Patients With Advanced Prostate Cancer is a phase 1/2 interventional study registered as NCT06139575 by Bivision Pharmaceuticals, Inc., with 90 participants planned, started 2023-12-22 and due to reach its primary completion in 2026-05. Interventions recorded: Lutetium Lu 177 JH020002 Injection.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06139575","url":"https://clinicaltrials.gov/study/NCT06139575"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06139575","phase":"1/2","setting":"Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Preliminary Efficacy of Lutetium Lu 177 JH020002 Injection in Patients With Advanced Prostate Cancer","sponsor":"Bivision Pharmaceuticals, Inc.","enrolled":90,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06139575/"}
{"id":"nct06184035","kind":"trial","name":"A Dose Escalation and Expansion Study of [177Lu]Lu-SN201 in Participants With Advanced Cancer","aka":[],"tldr":"A phase 1/2 trial of [177Lu]Lu-SN201 in advanced solid tumours, run by Spago Nanomedical AB, now recruiting.","summary":"A Dose Escalation and Expansion Study of [177Lu]Lu-SN201 in Participants With Advanced Cancer is a phase 1/2 interventional study registered as NCT06184035 by Spago Nanomedical AB, with 90 participants planned, started 2023-12-06 and due to reach its primary completion in 2027-12-01. Interventions recorded: [177Lu]Lu-SN201.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06184035","url":"https://clinicaltrials.gov/study/NCT06184035"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":[],"sections":[],"technologies":["lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06184035","phase":"1/2","setting":"Ph I/IIa Escalation/Expansion FIH, Open, Multi Center, Single Arm Study Evaluating Safety, Dosimetry and Early Efficacy of 177Lu-SN201 in Progressive/Treatment-refractory, Locally Advanced, Unresectable Metastatic or Recurrent Solid Tumors","sponsor":"Spago Nanomedical AB","enrolled":90,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06184035/"}
{"id":"nct06235151","kind":"trial","name":"Copper Cu 64 PSMA I&T PET Imaging in Men With Newly Diagnosed Prostate Cancer","aka":[],"tldr":"A phase 3 trial of Copper Cu 64 PSMA I&T in prostate cancer, run by Curium US LLC, active and no longer recruiting.","summary":"Copper Cu 64 PSMA I&T PET Imaging in Men With Newly Diagnosed Prostate Cancer is a phase 3 interventional study registered as NCT06235151 by Curium US LLC, with 439 participants enrolled, started 2024-04-01 and due to reach its primary completion in 2026-09. Interventions recorded: Copper Cu 64 PSMA I&T.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06235151","url":"https://clinicaltrials.gov/study/NCT06235151"}],"tags":["pipeline","ctgov-ingest"],"related":["cu-64"],"indications":["prostate","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06235151","phase":"3","setting":"Phase 3, Multi-Center, Open-label Study to Test the Diagnostic Performance of Copper Cu 64 PSMA I&T PET/CT in Staging Men With Newly Diagnosed Unfavorable Intermediate-risk, High-risk or Very High-risk Prostate Cancer Electing to Undergo Radical Prostatectomy With Pelvic Lymph Node Dissection","sponsor":"Curium US LLC","enrolled":439,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06235151/"}
{"id":"nct06247995","kind":"trial","name":"A Phase I/II, Dose Finding and Optimization Study of [177Lu]Lu-NeoB in Combination With Capecitabine in Patients With GRPR+, ER+, HER2- Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.","aka":["NeoB-Cap1"],"tldr":"A phase 1/2 trial of Capecitabine in advanced solid tumours, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"A Phase I/II, Dose Finding and Optimization Study of [177Lu]Lu-NeoB in Combination With Capecitabine in Patients With GRPR+, ER+, HER2- Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor. is a phase 1/2 interventional study registered as NCT06247995 by Novartis Pharmaceuticals, with 20 participants enrolled, started 2024-08-14 and due to reach its primary completion in 2027-04-14. Interventions recorded: [68Ga]Ga-NeoB, [177Lu]Lu-NeoB and Capecitabine.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06247995","url":"https://clinicaltrials.gov/study/NCT06247995"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06247995","phase":"1/2","setting":"A Phase I/II, Open-label, Multi-center Trial of [177Lu]Lu-NeoB in Combination With Capecitabine in Adult Patients With Gastrin Releasing Peptide Receptor Positive, Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor-2 Negative Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.","sponsor":"Novartis Pharmaceuticals","enrolled":20,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06247995/"}
{"id":"nct06298916","kind":"trial","name":"64Cu-LNTH-1363S in Patients With Sarcoma or Gastrointestinal Tract Cancer","aka":["PHANTOM"],"tldr":"A phase 1/2 trial of 64Cu-LNTH-1363S in sarcomas, oesophageal cancer, gastric & gastro-oesophageal junction cancer, pancreatic ductal adenocarcinoma and colorectal cancer, run by Lantheus Medical Imaging, now recruiting.","summary":"64Cu-LNTH-1363S in Patients With Sarcoma or Gastrointestinal Tract Cancer is a phase 1/2 interventional study registered as NCT06298916 by Lantheus Medical Imaging, with 26 participants planned, started 2025-08 and due to reach its primary completion in 2025-11. Interventions recorded: 64Cu-LNTH-1363S.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06298916","url":"https://clinicaltrials.gov/study/NCT06298916"}],"tags":["pipeline","ctgov-ingest"],"related":["cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06298916","phase":"1/2","setting":"A Phase 1/2a Study Utilizing 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) in Patients With Sarcoma or Gastrointestinal Tract Cancer (PHANTOM Trial)","sponsor":"Lantheus Medical Imaging","enrolled":26,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06298916/"}
{"id":"nct06359847","kind":"trial","name":"Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer","aka":[],"tldr":"A phase 2 trial of ST-1898 tablets in thyroid cancer, run by Beijing Scitech-Mq Pharmaceuticals Limited, now recruiting.","summary":"Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer is a phase 2 interventional study registered as NCT06359847 by Beijing Scitech-Mq Pharmaceuticals Limited, with 60 participants planned, started 2023-11-15 and due to reach its primary completion in 2027-12. Interventions recorded: ST-1898 tablets.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06359847","url":"https://clinicaltrials.gov/study/NCT06359847"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06359847","phase":"2","setting":"A Multicenter, Phase II Clinical Trial to Evaluate the Efficacy and Safety of ST-1898 Tablets in Patients With Locally Advanced or Metastatic RAIR-DTC After Failure of at Least First-line TKI Systemic Therapy","sponsor":"Beijing Scitech-Mq Pharmaceuticals Limited","enrolled":60,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06359847/"}
{"id":"nct06369831","kind":"trial","name":"HER2 Targeted Molecular Imaging in mBC and Other Metastatic Solid Carcinomas Using 68Ga-ABS011","aka":["HERMIA"],"tldr":"A phase 2 trial of an investigational treatment in advanced solid tumours, run by Abscint NV/SA, now recruiting.","summary":"HER2 Targeted Molecular Imaging in mBC and Other Metastatic Solid Carcinomas Using 68Ga-ABS011 is a phase 2 interventional study registered as NCT06369831 by Abscint NV/SA, with 60 participants planned, started 2024-09-12 and due to reach its primary completion in 2026-09.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06369831","url":"https://clinicaltrials.gov/study/NCT06369831"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68"],"indications":[],"sections":[],"technologies":["pet","pet-ct"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06369831","phase":"2","setting":"Evaluating the Diagnostic Performance of Human Epidermal Growth Factor Receptor 2 (HER2) Targeted Positron Emission Tomography and Computed Tomography (PET/CT) With 68Ga-ABS011 in Metastatic Breast Cancer (mBC) and Other Metastatic Solid Carcinomas.","sponsor":"Abscint NV/SA","enrolled":60,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06369831/"}
{"id":"nct06383052","kind":"trial","name":"A Phase 1/2 Study of 177Lu-NYM032 Injection in mCRPC","aka":[],"tldr":"A phase 1/2 trial of 177Lu-NYM032 injection in prostate cancer, run by Norroy Bioscience Co., LTD, active and no longer recruiting.","summary":"A Phase 1/2 Study of 177Lu-NYM032 Injection in mCRPC is a phase 1/2 interventional study registered as NCT06383052 by Norroy Bioscience Co., LTD, with 30 participants enrolled, started 2024-04-26 and due to reach its primary completion in 2025-06-30. Interventions recorded: 177Lu-NYM032 injection.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06383052","url":"https://clinicaltrials.gov/study/NCT06383052"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06383052","phase":"1/2","setting":"A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, Radiation Dosimetry and Efficacy of 177Lu-NYM032 Injection in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer","sponsor":"Norroy Bioscience Co., LTD","enrolled":30,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06383052/"}
{"id":"nct06398444","kind":"trial","name":"A Clinical Study of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Neuroendocrine Neoplasms","aka":[],"tldr":"A phase 2/3 trial of Lutetium[177Lu] Oxodotreotide Injection in neuroendocrine tumours, run by Sinotau Pharmaceutical Group, now recruiting.","summary":"A Clinical Study of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Neuroendocrine Neoplasms is a phase 2/3 interventional study registered as NCT06398444 by Sinotau Pharmaceutical Group, with 85 participants planned, started 2024-06-11 and due to reach its primary completion in 2027-06-01. Interventions recorded: Lutetium[177Lu] Oxodotreotide Injection.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06398444","url":"https://clinicaltrials.gov/study/NCT06398444"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["sinotau-pharmaceutical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06398444","phase":"2/3","setting":"A Clinical Study to Evaluate the Safety and Efficacy of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Somatostatin Receptor Positive Neuroendocrine Neoplasms","sponsor":"Sinotau Pharmaceutical Group","enrolled":85,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06398444/"}
{"id":"nct06474806","kind":"trial","name":"Safety and Diagnostic Performance of uPAR PET Imaging in Localised, Untreated Prostate Cancer","aka":["uTRACE-101"],"tldr":"A phase 2 trial of 64Cu-DOTA-AE105 in prostate cancer, run by Curasight, now recruiting.","summary":"Safety and Diagnostic Performance of uPAR PET Imaging in Localised, Untreated Prostate Cancer is a phase 2 interventional study registered as NCT06474806 by Curasight, with 168 participants planned, started 2024-06-01 and due to reach its primary completion in 2027-01-30. Interventions recorded: 64Cu-DOTA-AE105.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06474806","url":"https://clinicaltrials.gov/study/NCT06474806"}],"tags":["pipeline","ctgov-ingest"],"related":["cu-64"],"indications":["prostate"],"sections":[],"technologies":["pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06474806","phase":"2","setting":"An Open-label, Two-part, Phase 2 Clinical Trial to Investigate the Safety and Diagnostic Performance of uPAR PET Imaging for Non-invasive Classification of ISUP Grades Among Patients With Localised, Untreated Prostate Cancer.","sponsor":"Curasight","enrolled":168,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06474806/"}
{"id":"nct06504147","kind":"trial","name":"A Study of Radspherin® in Patients With Primary Advanced Epithelial Cancer, With Peritoneal Metastasis That Are Homologous Recombination Proficient Scheduled to Undergo Neoadjuvant Chemotherapy and Interval Debulking Surgery","aka":[],"tldr":"A phase 2 trial of Radspherin in ovarian cancer, run by Oncoinvent Solutions AS, now recruiting.","summary":"A Study of Radspherin® in Patients With Primary Advanced Epithelial Cancer, With Peritoneal Metastasis That Are Homologous Recombination Proficient Scheduled to Undergo Neoadjuvant Chemotherapy and Interval Debulking Surgery is a phase 2 interventional study registered as NCT06504147 by Oncoinvent Solutions AS, with 114 participants planned, started 2024-06-15 and due to reach its primary completion in 2028-02-29. Interventions recorded: Radspherin.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06504147","url":"https://clinicaltrials.gov/study/NCT06504147"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06504147","phase":"2","setting":"A Phase 2, Randomised, Open Label, Multicentre Study of an Intraperitoneal α-emitting Radionuclide Therapy (Radspherin®) in Patients With Primary Advanced High-grade Serous or High-grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, With Peritoneal Metastasis That Are Homologous Recombination Proficient and Scheduled to Undergo Neoadjuvant Chemotherapy and Interval Debulking Surgery","sponsor":"Oncoinvent Solutions AS","enrolled":114,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06504147/"}
{"id":"nct06505395","kind":"trial","name":"A Trial to Assess Efficacy, Safety, Pharmacokinetics of Octreotide Subcutaneous Injection in Patients With Gastroentero-pancreatic Neuroendocrine Tumor (GEP-NET)","aka":[],"tldr":"A phase 2 trial of SYHX2008 injection in pancreatic ductal adenocarcinoma, run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd., now recruiting.","summary":"A Trial to Assess Efficacy, Safety, Pharmacokinetics of Octreotide Subcutaneous Injection in Patients With Gastroentero-pancreatic Neuroendocrine Tumor (GEP-NET) is a phase 2 interventional study registered as NCT06505395 by CSPC ZhongQi Pharmaceutical Technology Co., Ltd., with 90 participants planned, started 2024-07-30 and due to reach its primary completion in 2027-08-01. Interventions recorded: SYHX2008 injection and Sandostatin LAR@.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06505395","url":"https://clinicaltrials.gov/study/NCT06505395"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06505395","phase":"2","setting":"A Phase Ⅱ Randomized, Parallel-group, Open-label, Active-controlled Trial to Assess the Efficacy, Safety and Pharmacokinetics of the Long-acting Octreotide Subcutaneous Injection (SYHX2008) Versus Octreotide Microspheres (Sandostatin LAR@) in Patients With GEP-NET","sponsor":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd.","enrolled":90,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06505395/"}
{"id":"nct06520345","kind":"trial","name":"The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global)","aka":[],"tldr":"A phase 3 trial of FAP-2286, Enzalutamide, Abiraterone acetate in prostate cancer, run by Telix Pharmaceuticals (Innovations) Pty Limited, now recruiting.","summary":"The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global) is a phase 3 interventional study registered as NCT06520345 by Telix Pharmaceuticals (Innovations) Pty Limited, with 520 participants planned, started 2024-07-26 and due to reach its primary completion in 2027-12. Interventions recorded: 177Lu-TLX591, Enzalutamide, Abiraterone, Docetaxel. Conditions listed: Metastatic Castration-resistant Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06520345","url":"https://clinicaltrials.gov/study/NCT06520345"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286","enzalutamide","abiraterone","docetaxel"],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06520345","phase":"3","setting":"A Multinational, Multicenter, Prospective, Randomized, Controlled, Open-Label, Phase 3 Study of Lutetium (177Lu) Rosopatamab Tetraxetan in Combination With Standard of Care Versus Standard of Care Alone in Patients With PSMA Positive Metastatic Castration-Resistant Prostate Cancer Previously After Androgen Receptor Pathway Inhibitor Treatment","sponsor":"Telix Pharmaceuticals (Innovations) Pty Limited","enrolled":520,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06520345/"}
{"id":"nct06549465","kind":"trial","name":"Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer (CRPC)","aka":[],"tldr":"A phase 2 trial of the actinium-225 antibody rosopatamab tetraxetan (with an indium-111 version for dosimetry) in prostate cancer, run by Convergent Therapeutics, now recruiting.","summary":"Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer (CRPC) is a phase 2 interventional study registered as NCT06549465 by Convergent Therapeutics, with 93 participants planned, started 2024-08-06 and due to reach its primary completion in August 2027 (estimated; moved from 20 April 2027 in the registry update of 2 October 2026). Interventions recorded: In-111 rosopatamab tetraxetan, 45 kBq/kg Ac-225 rosopatamab tetraxetan, 45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan, 60 kBq/kg Ac-225 rosopatamab tetraxetan, Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan and Single dose 34 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan.","status":"recruiting","asOf":"2026-10-11","links":[{"label":"ClinicalTrials.gov NCT06549465","url":"https://clinicaltrials.gov/study/NCT06549465"}],"tags":["pipeline","ctgov-ingest"],"related":["in-111","ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["convergent-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06549465","phase":"2","setting":"A Phase 2, Open-label Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer","sponsor":"Convergent Therapeutics","enrolled":93,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06549465/"}
{"id":"nct06569420","kind":"trial","name":"Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC","aka":[],"tldr":"A phase 3 trial of an investigational treatment in non-small-cell lung cancer, run by Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., active and no longer recruiting.","summary":"Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC is a phase 3 interventional study registered as NCT06569420 by Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., with 275 participants enrolled, started 2021-12-31 and due to reach its primary completion in 2025-07-31.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06569420","url":"https://clinicaltrials.gov/study/NCT06569420"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06569420","phase":"3","setting":"A Randomized, Multicenter, Phase III Open-label Study: Efficacy and Safety of Comparing SAF-189s With Crizotinib in First-line Anaplastic Lymphoma Kinase-positive Advanced and Metastatic NSCLC","sponsor":"Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.","enrolled":275,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06569420/"}
{"id":"nct06590857","kind":"trial","name":"Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.","aka":["TRACY-1"],"tldr":"A phase 1/2 trial of Actinium-225 DOTATATE in HR-positive / HER2-negative breast cancer, run by RayzeBio, Inc., active and no longer recruiting.","summary":"Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. is a phase 1/2 interventional study registered as NCT06590857 by RayzeBio, Inc., with 16 participants enrolled, started 2024-07-19 and due to reach its primary completion in 2028-10. Interventions recorded: RYZ101 and Standard of Care Endocrine Therapy.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06590857","url":"https://clinicaltrials.gov/study/NCT06590857"}],"tags":["pipeline","ctgov-ingest"],"related":["ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["ryz101"],"companies":["rayzebio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06590857","phase":"1/2","setting":"Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) in Subjects With Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) (TRACY-1).","sponsor":"RayzeBio, Inc.","enrolled":16,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06590857/"}
{"id":"nct06710756","kind":"trial","name":"Lead-212 PSV359 Therapy for Patients With Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of [203Pb]Pb-PSV359 in pancreatic ductal adenocarcinoma, gastric & gastro-oesophageal junction cancer, oesophageal cancer, colorectal cancer, ovarian cancer and head and neck squamous cell carcinoma, run by Perspective Therapeutics, now recruiting.","summary":"Lead-212 PSV359 Therapy for Patients With Solid Tumors is a phase 1/2 interventional study registered as NCT06710756 by Perspective Therapeutics, with 112 participants planned, started 2025-04-28 and due to reach its primary completion in 2028-01-31. Interventions recorded: [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06710756","url":"https://clinicaltrials.gov/study/NCT06710756"}],"tags":["pipeline","ctgov-ingest"],"related":["pb-212"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["perspective-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06710756","phase":"1/2","setting":"A Phase I/IIa Image-Guided, Alpha-Particle Therapy Study of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359 in Patients With Solid Tumors That Are Known to be Fibroblast Activation Protein (FAP)-Positive","sponsor":"Perspective Therapeutics","enrolled":112,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06710756/"}
{"id":"nct06726161","kind":"trial","name":"Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC","aka":[],"tldr":"A phase 1/2 trial of RYZ801 in hepatocellular carcinoma, run by RayzeBio, Inc., now recruiting.","summary":"Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC is a phase 1/2 interventional study registered as NCT06726161 by RayzeBio, Inc., with 590 participants planned, started 2025-09-05 and due to reach its primary completion in 2030-06. Interventions recorded: RYZ801.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06726161","url":"https://clinicaltrials.gov/study/NCT06726161"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["rayzebio"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06726161","phase":"1/2","setting":"Phase 1/2 Randomized, Controlled, Open-label Trial of Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ Unresectable Hepatocellular Carcinoma (HCC)","sponsor":"RayzeBio, Inc.","enrolled":590,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06726161/"}
{"id":"nct06750419","kind":"trial","name":"89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study","aka":["ZIRCON-CP"],"tldr":"A phase 3 trial of Zirconium-89 girentuximab run by Telix Pharmaceuticals (Innovations) Pty Limited in renal cell carcinoma, now recruiting.","summary":"89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study is a phase 3 interventional study registered as NCT06750419 by Telix Pharmaceuticals (Innovations) Pty Limited, with 82 participants planned, started 2024-11-06. Conditions listed: Clear Cell Renal Cell Carcinoma. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06750419","url":"https://clinicaltrials.gov/study/NCT06750419"}],"tags":["ctgov-ingest"],"related":["zr-89"],"indications":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["girentuximab-zr89"],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06750419","phase":"3","setting":"A Confirmatory, Open-label, Single-arm, Multi-centre Study to Evaluate Safety, Tolerability and Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) to Non-invasively Detect Clear Cell Renal Cell Carcinoma (ccRCC) by Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Chinese Patients With Indeterminate Renal Masses (ZIRCON-CP Study)","sponsor":"Telix Pharmaceuticals (Innovations) Pty Limited","enrolled":82,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06750419/"}
{"id":"nct06754085","kind":"trial","name":"Study of 18F-Florastamin PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer","aka":[],"tldr":"A phase 3 trial of Florastamin[18F] Injection in prostate cancer, run by HTA Co., Ltd., completed in June 2026 with no results posted yet.","summary":"Study of 18F-Florastamin PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer is a phase 3 interventional study registered as NCT06754085 by HTA Co., Ltd., with 131 participants enrolled (actual), started 2024-12-19 and completed on 2026-06-11 (primary completion and study completion both actual, per ClinicalTrials.gov, last updated 2026-09-25). Interventions recorded: Florastamin[18F] Injection.","status":"completed","asOf":"2026-10-04","links":[{"label":"ClinicalTrials.gov NCT06754085","url":"https://clinicaltrials.gov/study/NCT06754085"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":["florastamin-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06754085","phase":"3","setting":"A Phase III, Prospective, Open-Label, Single-Arm, Multi-center Clinical Study to Assess the Diagnostic Performance and Safety of 18F-Florastamin PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer","sponsor":"HTA Co., Ltd.","enrolled":131,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06754085/"}
{"id":"nct06777433","kind":"trial","name":"Phase 2b Imaging Study of RAD101 in Participants With Suspected Recurrent Brain Metastases","aka":[],"tldr":"A phase 2 trial of RAD101 (18F-FPIA) in brain and spinal cord tumours, run by Radiopharm Theranostics, Ltd, active and no longer recruiting.","summary":"Phase 2b Imaging Study of RAD101 in Participants With Suspected Recurrent Brain Metastases is a phase 2 interventional study registered as NCT06777433 by Radiopharm Theranostics, Ltd, with 30 participants enrolled, started 2024-12-13 and due to reach its primary completion in 2026-04-23. Interventions recorded: RAD101 (18F-FPIA).","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06777433","url":"https://clinicaltrials.gov/study/NCT06777433"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["radiopharm-theranostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06777433","phase":"2","setting":"An Open-Label, Single Dose, Single Arm, Multicenter Phase 2b Study to Establish the Imaging Performance of RAD101 Positron Emission Tomography (PET) in Participants With Suspected Recurrent Brain Metastases From Solid Tumors","sponsor":"Radiopharm Theranostics, Ltd","enrolled":30,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06777433/"}
{"id":"nct06780670","kind":"trial","name":"Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy","aka":["PSMAcTION"],"tldr":"A phase 2/3 trial testing AAA817 in prostate cancer, now recruiting.","summary":"Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy is a phase 2/3 interventional study registered as NCT06780670, led by Novartis Pharmaceuticals, and recruiting on the registry. Official title: PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomised Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy. Planned enrolment is 443 participants (estimated). The study started in 2025-02-27 and primary completion is expected in 2028-06-27. No results have been posted on ClinicalTrials.gov.","status":"recruiting","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov NCT06780670","url":"https://clinicaltrials.gov/study/NCT06780670"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["aaa817"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06780670","phase":"2/3","setting":"PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy","sponsor":"Novartis Pharmaceuticals","enrolled":443,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06780670/"}
{"id":"nct06784752","kind":"trial","name":"Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET","aka":["NETTER-3"],"tldr":"A phase 3 trial of [177Lu]Lu-DOTA-TATE in pancreatic ductal adenocarcinoma, run by Novartis Pharmaceuticals, now recruiting.","summary":"Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET is a phase 3 interventional study registered as NCT06784752 by Novartis Pharmaceuticals, with 240 participants planned, started 2025-05-30 and due to reach its primary completion in 2028-12-08. Interventions recorded: [177Lu]Lu-DOTA-TATE and Octreotide LAR.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06784752","url":"https://clinicaltrials.gov/study/NCT06784752"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06784752","phase":"3","setting":"A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients Newly Diagnosed With Grade 1 and Grade 2 (Ki-67 <10%) Advanced GEP-NET With High Disease Burden (NETTER-3)","sponsor":"Novartis Pharmaceuticals","enrolled":240,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06784752/"}
{"id":"nct06855277","kind":"trial","name":"Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC","aka":["AcTFirst"],"tldr":"A phase 3 trial testing AAA817 in prostate cancer, now recruiting.","summary":"Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC is a phase 3 interventional study registered as NCT06855277, led by Novartis Pharmaceuticals, and recruiting on the registry. Official title: A Phase III, Open-label, Multi-centre, Randomised Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer. Planned enrolment is 940 participants (estimated). The study started in 2025-07-01 and primary completion is expected in 2028-09-29. No results have been posted on ClinicalTrials.gov.","status":"recruiting","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov NCT06855277","url":"https://clinicaltrials.gov/study/NCT06855277"}],"tags":["ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["aaa817"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06855277","phase":"3","setting":"A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer","sponsor":"Novartis Pharmaceuticals","enrolled":940,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06855277/"}
{"id":"nct06860971","kind":"trial","name":"A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma","aka":[],"tldr":"A phase 3 trial testing AL2846 in thyroid cancer, now recruiting.","summary":"A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma is a phase 3 interventional study registered as NCT06860971, led by Chia Tai Tianqing Pharmaceutical, and recruiting on the registry. Official title: A Randomised, Double-Blind, Multicenter Phase III Clinical Trial Evaluating AL2846 Capsule Versus Placebo in Patients With Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma Who Failed Prior VEGFR-Targeted Therapy. Planned enrolment is 144 participants (estimated). The study started in 2025-04-18 and primary completion is expected in 2027-01. No results have been posted on ClinicalTrials.gov.","status":"recruiting","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov NCT06860971","url":"https://clinicaltrials.gov/study/NCT06860971"}],"tags":["ctgov-ingest"],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":["al2846"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06860971","phase":"3","setting":"A Randomized, Double-Blind, Multicenter Phase III Clinical Trial Evaluating AL2846 Capsule Versus Placebo in Patients With Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma Who Failed Prior VEGFR-Targeted Therapy","sponsor":"Chia Tai Tianqing Pharmaceutical","enrolled":144,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06860971/"}
{"id":"nct06894511","kind":"trial","name":"An Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC","aka":["PSMAndARPI"],"tldr":"A phase 2 trial of FAP-2286, Lutetium-177 vipivotide tetraxetan in prostate cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"An Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC is a phase 2 interventional study registered as NCT06894511 by Novartis Pharmaceuticals, with 7 participants enrolled, started 2025-09-11 and due to reach its primary completion in 2026-10-15. Interventions recorded: AAA617, ARPI: Abiraterone, ARPI: Enzalutamide. Conditions listed: Metastatic Castration Resistant Prostate Cancer (mCRPC). No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06894511","url":"https://clinicaltrials.gov/study/NCT06894511"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286","pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06894511","phase":"2","setting":"A Phase II, Open-label, Multi-Center, Randomized Study of Combination of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) and Androgen Receptor Pathway Inhibitor (ARPI) vs. Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in First-line Treatment of Patients With Prostate-Specific Membrane Antigen (PSMA)-Positive Progressive Metastatic Castration Resistant Prostate Cancer (mCRPC)","sponsor":"Novartis Pharmaceuticals","enrolled":7,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06894511/"}
{"id":"nct06906471","kind":"trial","name":"A Single-Arm, Blinded, Fluorescent PSMA Histopathology Trial of AS1986NS","aka":[],"tldr":"A phase 1/2 trial of AS1986NS in prostate cancer, run by Antelope Surgical Solutions, Inc, now recruiting.","summary":"A Single-Arm, Blinded, Fluorescent PSMA Histopathology Trial of AS1986NS is a phase 1/2 interventional study registered as NCT06906471 by Antelope Surgical Solutions, Inc, with 10 participants planned, started 2026-07-01 and due to reach its primary completion in 2026-10-30. Interventions recorded: AS1986NS.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06906471","url":"https://clinicaltrials.gov/study/NCT06906471"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06906471","phase":"1/2","setting":"A Single-Arm, Blinded, Fluorescent PSMA Histopathology Trial of AS1986NS","sponsor":"Antelope Surgical Solutions, Inc","enrolled":10,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06906471/"}
{"id":"nct06909825","kind":"trial","name":"FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)","aka":[],"tldr":"A phase 2 trial of FPI-2265, Olaparib in prostate cancer, run by Fusion Pharmaceuticals Inc., active and no longer recruiting.","summary":"FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) is a phase 2 interventional study registered as NCT06909825 by Fusion Pharmaceuticals Inc., with 85 participants planned, started 2025-02-26 and due to reach its primary completion in 2027-05. Interventions recorded: FPI-2265, Olaparib. Conditions listed: Metastatic Castration-resistant Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06909825","url":"https://clinicaltrials.gov/study/NCT06909825"}],"tags":["ctgov-ingest"],"related":["ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fpi-2265","olaparib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06909825","phase":"2","setting":"A Phase 2, Open-label, Multi-centre Study of FPI-2265 (225Ac-PSMA-I&T) and Olaparib in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)","sponsor":"Fusion Pharmaceuticals Inc.","enrolled":85,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06909825/"}
{"id":"nct06925581","kind":"trial","name":"A Trial of HRS-6768 in Patients With Advanced Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of HRS-6768 in advanced solid tumours, run by Jiangsu HengRui Medicine Co., Ltd., now recruiting.","summary":"A Trial of HRS-6768 in Patients With Advanced Solid Tumors is a phase 1/2 interventional study registered as NCT06925581 by Jiangsu HengRui Medicine Co., Ltd., with 84 participants planned, started 2025-04-24 and due to reach its primary completion in 2026-04. Interventions recorded: HRS-6768.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06925581","url":"https://clinicaltrials.gov/study/NCT06925581"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06925581","phase":"1/2","setting":"A Phase I/II Clinical Trial to Evaluate the Pharmacokinetics, Radiation Dosimetry, Safety and Preliminary Efficacy of HRS-6768 in the Treatment of Patients With Advanced Solid Tumors","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","enrolled":84,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06925581/"}
{"id":"nct06990880","kind":"trial","name":"A Study of GSK5458514 Administered Alone or In Combination With Other Anti-Cancer Agents in Participants With Prostate Cancer","aka":[],"tldr":"A phase 1/2 trial of GSK5458514 in prostate cancer, run by GlaxoSmithKline, now recruiting.","summary":"A Study of GSK5458514 Administered Alone or In Combination With Other Anti-Cancer Agents in Participants With Prostate Cancer is a phase 1/2 interventional study registered as NCT06990880 by GlaxoSmithKline, with 85 participants planned, started 2025-06-12 and due to reach its primary completion in 2027-10-26. Interventions recorded: GSK5458514.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT06990880","url":"https://clinicaltrials.gov/study/NCT06990880"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06990880","phase":"1/2","setting":"A Phase 1/2 First-Time-In-Human, Open-Label, Multicenter, Dose Escalation and Expansion Study of GSK5458514 PSMA Targeting T Cell Engager Alone or in Combination With Other Anti-Cancer Agents in Adult Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)","sponsor":"GlaxoSmithKline","enrolled":85,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct06990880/"}
{"id":"nct07047118","kind":"trial","name":"A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)","aka":[],"tldr":"A phase 2 trial of JSB462 in prostate cancer, run by Novartis Pharmaceuticals, active and no longer recruiting.","summary":"A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) is a phase 2 interventional study registered as NCT07047118 by Novartis Pharmaceuticals, with 138 participants enrolled, started 2025-07-03 and due to reach its primary completion in 2027-07-16. Interventions recorded: JSB462 and AAA617.","status":"active","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07047118","url":"https://clinicaltrials.gov/study/NCT07047118"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["advanced-accelerator-applications"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07047118","phase":"2","setting":"A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Lutetium (177Lu) Vipivotide Tetraxetan in Adult Male Patients With PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC)","sponsor":"Novartis Pharmaceuticals","enrolled":138,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07047118/"}
{"id":"nct07052214","kind":"trial","name":"PSMA PET Combined With MRI for the Detection of PCa","aka":["BiPASS"],"tldr":"A phase 3 trial of Gallium-68 gozetotide in prostate cancer, run by Telix Pharmaceuticals (Innovations) Pty Limited, now recruiting.","summary":"PSMA PET Combined With MRI for the Detection of PCa is a phase 3 interventional study registered as NCT07052214 by Telix Pharmaceuticals (Innovations) Pty Limited, with 338 participants planned, started 2025-08-18 and due to reach its primary completion in 2027-01. Interventions recorded: 68Ga-PSMA-11. Conditions listed: PCA, Prostate Cancer, Prostatic Neoplasm, PSMA PET. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07052214","url":"https://clinicaltrials.gov/study/NCT07052214"}],"tags":["ctgov-ingest"],"related":["ga-68"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["ga68-psma-11"],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07052214","phase":"3","setting":"A Single Arm, Multicenter, Prospective, Open Label, Longitudinal Phase 3 Study of Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) Combined With Magnetic Resonance Imaging (MRI) Compared to Standard of Care (SOC) for the Detection of Prostate Cancer (PCa).","sponsor":"Telix Pharmaceuticals (Innovations) Pty Limited","enrolled":338,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07052214/"}
{"id":"nct07070349","kind":"trial","name":"A Trial of HRS-6213 in Healthy Subjects and Patients With Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of HRS-6213 in advanced solid tumours, run by Jiangsu HengRui Medicine Co., Ltd., now recruiting.","summary":"A Trial of HRS-6213 in Healthy Subjects and Patients With Solid Tumors is a phase 1/2 interventional study registered as NCT07070349 by Jiangsu HengRui Medicine Co., Ltd., with 48 participants planned, started 2025-07-10 and due to reach its primary completion in 2026-01. Interventions recorded: HRS-6213.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07070349","url":"https://clinicaltrials.gov/study/NCT07070349"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07070349","phase":"1/2","setting":"A Phase I/II Clinical Study to Evaluate the Safety, Radiation Dosimetry, Pharmacokinetics, and Preliminary Diagnostic Efficacy of HRS-6213 in Healthy Subjects and Patients With Solid Tumors","sponsor":"Jiangsu HengRui Medicine Co., Ltd.","enrolled":48,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07070349/"}
{"id":"nct07129252","kind":"trial","name":"A Study to Investigate Safety and Effectiveness of CRN09682 in Participants With SST2-Expressing NENs and Other Solid Tumors","aka":["BRAVESST2"],"tldr":"A phase 1/2 trial of CRN09682 in neuroendocrine tumours, run by Crinetics Pharmaceuticals Inc., now recruiting.","summary":"A Study to Investigate Safety and Effectiveness of CRN09682 in Participants With SST2-Expressing NENs and Other Solid Tumors is a phase 1/2 interventional study registered as NCT07129252 by Crinetics Pharmaceuticals Inc., with 150 participants planned, started 2025-11-26 and due to reach its primary completion in 2027-08. Interventions recorded: CRN09682.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07129252","url":"https://clinicaltrials.gov/study/NCT07129252"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07129252","phase":"1/2","setting":"A Phase 1/2 Dose Escalation Study of CRN09682 With an Expansion Phase in Participants With Progressive Metastatic Somatostatin Receptor Type 2 (SST2)-Expressing Neuroendocrine Neoplasms (NENs) and Other SST2-Expressing Solid Tumors","sponsor":"Crinetics Pharmaceuticals Inc.","enrolled":150,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07129252/"}
{"id":"nct07189871","kind":"trial","name":"177Lu-BetaBart in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of 177Lu-BetaBart in prostate cancer, colorectal cancer, non-small-cell lung cancer, ovarian cancer, cervical cancer and endometrial cancer, run by Radiopharm Theranostics, Ltd, now recruiting.","summary":"177Lu-BetaBart in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors is a phase 1/2 interventional study registered as NCT07189871 by Radiopharm Theranostics, Ltd, with 61 participants planned, started 2026-02-23 and due to reach its primary completion in 2027-12. Interventions recorded: 177Lu-BetaBart.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07189871","url":"https://clinicaltrials.gov/study/NCT07189871"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["radiopharm-theranostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07189871","phase":"1/2","setting":"A Phase 1/2a Study of the Safety, Tolerability, and Preliminary Clinical Activity of 177LuBetaBart, a 177Lu-Labeled Anti-B7-H3 Monoclonal Antibody, in Patients With Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors","sponsor":"Radiopharm Theranostics, Ltd","enrolled":61,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07189871/"}
{"id":"nct07197580","kind":"trial","name":"Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC","aka":["LUTEON"],"tldr":"A phase 3 trial of 177Lu-TLX250 in renal cell carcinoma, run by Telix Pharmaceuticals (Innovations) Pty Limited, now recruiting.","summary":"Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC is a phase 3 interventional study registered as NCT07197580 by Telix Pharmaceuticals (Innovations) Pty Limited, with 40 participants planned, started 2026-03-25 and due to reach its primary completion in 2027-08-31. Interventions recorded: 177Lu-TLX250.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07197580","url":"https://clinicaltrials.gov/study/NCT07197580"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07197580","phase":"3","setting":"A Phase 3, Randomized, Multi-Center, Open-Label Study to Compare 177Lu-TLX250 (Lutetium (177Lu) Girentuximab Tetraxetan) With the Investigator's Choice of a Single Agent Therapy in Participants With Carbonic Anhydrase 9 (CAIX) Expressing, Advanced Relapsed or Recurrent Clear Cell Renal Cell Carcinoma (ccRCC)","sponsor":"Telix Pharmaceuticals (Innovations) Pty Limited","enrolled":40,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07197580/"}
{"id":"nct07217704","kind":"trial","name":"Using 18F-FAPI PET to Detect Metastatic Disease in Patients That Have Gastric or Esophageal Cancer.","aka":[],"tldr":"A phase 3 trial of [18F]FAPI-74 PET/CT in oesophageal cancer and gastric & gastro-oesophageal junction cancer, run by SOFIE, now recruiting.","summary":"Using 18F-FAPI PET to Detect Metastatic Disease in Patients That Have Gastric or Esophageal Cancer. is a phase 3 interventional study registered as NCT07217704 by SOFIE, with 200 participants planned, started 2025-11-14 and due to reach its primary completion in 2027-08-30. Interventions recorded: [18F]FAPI-74 PET/CT.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07217704","url":"https://clinicaltrials.gov/study/NCT07217704"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["sofie-biosciences"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07217704","phase":"3","setting":"A Phase 3, Multicenter, Prospective Open-Label Study of the Diagnostic Performance of [¹⁸F]FAPI-74 PET/CT for the Detection of Metastatic Disease in Adults With Gastric or Esophageal Cancer","sponsor":"SOFIE","enrolled":200,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07217704/"}
{"id":"nct07219238","kind":"trial","name":"Study to Evaluate the Diagnostic Performance of GEH300079 (68Ga) Injection PET/CT for Detection of PC in Patients With Colorectal, Gastric, Ovarian, o","aka":["PERISCOPE"],"tldr":"A phase 2/3 trial of FAP-2286 in colorectal cancer and ovarian cancer, run by GE Healthcare, now recruiting.","summary":"Study to Evaluate the Diagnostic Performance of GEH300079 (68Ga) Injection PET/CT for Detection of PC in Patients With Colorectal, Gastric, Ovarian, or Pancreatic Cancers (PERISCOPE) is a phase 2/3 interventional study registered as NCT07219238 by GE Healthcare, with 175 participants planned, started 2026-10 and due to reach its primary completion in 2029-06. Interventions recorded: GEH300079 (68Ga) Injection Positron-Emission Tomography (PET)/Computed Tomography (CT). Conditions listed: Colorectal Cancer, Gastric Cancers, Ovarian Cancers, Pancreatic Ductal Adenocarcinoma. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07219238","url":"https://clinicaltrials.gov/study/NCT07219238"}],"tags":["ctgov-ingest"],"related":["ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["fap-2286"],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07219238","phase":"2/3","setting":"A Phase 2/3, Multicenter, Open-Label, Non-Randomized Study to Evaluate Diagnostic Performance of GEH300079 (68Ga) Injection Positron-Emission Tomography (PET)/Computed Tomography (CT) for Detection of Peritoneal Carcinomatosis (PC) in Patients With Colorectal, Gastric, Ovarian, or Pancreatic Cancers (PERISCOPE)","sponsor":"GE Healthcare","enrolled":175,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07219238/"}
{"id":"nct07226986","kind":"trial","name":"A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA","aka":[],"tldr":"A phase 1/2 trial of Enzalutamide, Abiraterone acetate in prostate cancer, run by Novartis Pharmaceuticals, now recruiting.","summary":"A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA-positive mCRPC is a phase 1/2 interventional study registered as NCT07226986 by Novartis Pharmaceuticals, with 123 participants planned, started 2025-12-05 and due to reach its primary completion in 2028-07-10. Interventions recorded: AMO959, AAA617, Enzalutamide, Abiraterone. Conditions listed: PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With Prior Exposure to One Prior ARPI Who Are Candidates for Taxane-based Chemotherapy. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07226986","url":"https://clinicaltrials.gov/study/NCT07226986"}],"tags":["ctgov-ingest"],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["enzalutamide","abiraterone"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07226986","phase":"1/2","setting":"A Phase Ib/II Open-label, Multi-center Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With an Androgen Receptor Pathway Inhibitor (ARPI) in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC)","sponsor":"Novartis Pharmaceuticals","enrolled":123,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07226986/"}
{"id":"nct07258407","kind":"trial","name":"A Clinical Trial Evaluating the Safety of TD001 In Patients With PSMA-Expressing Metastatic Prostate Cancer","aka":[],"tldr":"A phase 1/2 trial of TD001 in prostate cancer, run by T.O.A.D. Oncology SA, now recruiting.","summary":"A Clinical Trial Evaluating the Safety of TD001 In Patients With PSMA-Expressing Metastatic Prostate Cancer is a phase 1/2 interventional study registered as NCT07258407 by T.O.A.D. Oncology SA, with 180 participants planned, started 2026-01-30 and due to reach its primary completion in 2028-03. Interventions recorded: TD001.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07258407","url":"https://clinicaltrials.gov/study/NCT07258407"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07258407","phase":"1/2","setting":"A Phase 1/2 Dose Escalation Trial With Administration Schedule Exploration Evaluating Single Agent TD001, a PSMA-Targeted Antibody-Drug Conjugate, in Patients With PSMA-Expressing Metastatic Castration-Resistant Prostate Cancer","sponsor":"T.O.A.D. Oncology SA","enrolled":180,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07258407/"}
{"id":"nct07259213","kind":"trial","name":"A Study of Terbium 161 (161Tb)-RAD402 in Participants With CRPC","aka":[],"tldr":"A phase 1/2 trial of 161Tb RAD402 in prostate cancer, run by Radiopharm Theranostics, Ltd, now recruiting.","summary":"A Study of Terbium 161 (161Tb)-RAD402 in Participants With CRPC is a phase 1/2 interventional study registered as NCT07259213 by Radiopharm Theranostics, Ltd, with 73 participants planned, started 2026-03-05 and due to reach its primary completion in 2028-11-30. Interventions recorded: 161Tb RAD402.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07259213","url":"https://clinicaltrials.gov/study/NCT07259213"}],"tags":["pipeline","ctgov-ingest"],"related":["tb-161"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["radiopharm-theranostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07259213","phase":"1/2","setting":"A Phase 1/2a Study to Evaluate the Safety, Tolerability, Whole-Body Distribution, and Preliminary Clinical Activity of 161Tb-RAD402, a Radiolabeled Anti-Kallikrein-Related Peptidase 3 (KLK3) Monoclonal Antibody Targeting Free Prostate-Specific Antigen, in Participants With Castration-Resistant Prostate Cancer (CRPC)","sponsor":"Radiopharm Theranostics, Ltd","enrolled":73,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07259213/"}
{"id":"nct07276789","kind":"trial","name":"Efficacy and Safety of a Single Dose of LS301-IT for Fluorescence Intraoperative Molecular Imaging (IMI) for Patients Undergoing Lung Cancer Resection for Non Small Cell Lung Cancer","aka":[],"tldr":"A phase 2 trial of LS301-IT 0.1 mg/kg in non-small-cell lung cancer, run by Integro Theranostics, now recruiting.","summary":"Efficacy and Safety of a Single Dose of LS301-IT for Fluorescence Intraoperative Molecular Imaging (IMI) for Patients Undergoing Lung Cancer Resection for Non Small Cell Lung Cancer is a phase 2 interventional study registered as NCT07276789 by Integro Theranostics, with 35 participants planned, started 2025-12-08 and due to reach its primary completion in 2026-08. Interventions recorded: LS301-IT 0.1 mg/kg.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07276789","url":"https://clinicaltrials.gov/study/NCT07276789"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07276789","phase":"2","setting":"A Phase 2, Open-Label, Multicenter Study to Investigate the Efficacy and Safety of a Single Dose of LS301-IT for Fluorescence Intraoperative Molecular Imaging (IMI) for Lung Cancer Resection","sponsor":"Integro Theranostics","enrolled":35,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07276789/"}
{"id":"nct07278479","kind":"trial","name":"Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of [212Pb]Pb-MP0712 in neuroendocrine tumours, small-cell lung cancer, pancreatic ductal adenocarcinoma and bladder & urothelial cancer, run by Molecular Partners AG, now recruiting.","summary":"Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors is a phase 1/2 interventional study registered as NCT07278479 by Molecular Partners AG, with 138 participants planned, started 2026-05-18 and due to reach its primary completion in 2028-09. Interventions recorded: [212Pb]Pb-MP0712.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07278479","url":"https://clinicaltrials.gov/study/NCT07278479"}],"tags":["pipeline","ctgov-ingest"],"related":["pb-212"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["orano-med"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07278479","phase":"1/2","setting":"A Phase 1/2a Study to Assess Safety, Tolerability, and Efficacy of [212Pb]Pb-DOTAM-MAM279 in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors","sponsor":"Molecular Partners AG","enrolled":138,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07278479/"}
{"id":"nct07311694","kind":"trial","name":"A Phase III Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer","aka":[],"tldr":"A phase 3 trial testing HRS-4357 in prostate cancer, now recruiting.","summary":"A Phase III Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer is a phase 3 interventional study registered as NCT07311694, led by Jiangsu HengRui Medicine, and recruiting on the registry. Official title: A Phase III, Randomised, Open-Label, Multicenter Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer. Planned enrolment is 370 participants (estimated). The study started in 2026-02-02 and primary completion is expected in 2027-12. No results have been posted on ClinicalTrials.gov.","status":"recruiting","asOf":"2026-09-11","links":[{"label":"ClinicalTrials.gov NCT07311694","url":"https://clinicaltrials.gov/study/NCT07311694"}],"tags":["ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["hrs-4357"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07311694","phase":"3","setting":"A Phase III, Randomized, Open-Label, Multicenter Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer","sponsor":"Jiangsu HengRui Medicine","enrolled":370,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07311694/"}
{"id":"nct07357519","kind":"trial","name":"Lu-TARGO (177Lu-TARGeted Osteosarcoma Therapy)","aka":[],"tldr":"A phase 1/2 trial of LNTH2403 Phase 1 dose in osteosarcoma, run by Lantheus Medical Imaging, now recruiting.","summary":"Lu-TARGO (177Lu-TARGeted Osteosarcoma Therapy) is a phase 1/2 interventional study registered as NCT07357519 by Lantheus Medical Imaging, with 55 participants planned, started 2026-02-03 and due to reach its primary completion in 2027-08. Interventions recorded: LNTH2403 Phase 1 dose and Phase 2; LNTH2403 a single agent recommended phase 2 dose (RP2D)..","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07357519","url":"https://clinicaltrials.gov/study/NCT07357519"}],"tags":["pipeline","ctgov-ingest"],"related":["lu-177"],"indications":["osteosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07357519","phase":"1/2","setting":"A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, -Radiation Dosimetry, and Preliminary Anti-Neoplastic Activity of LNTH-2403, a LRRC15-targeted 177Lutetium-labeled Monoclonal Antibody, in Participants With Relapsed / Refractory Osteosarcoma","sponsor":"Lantheus Medical Imaging","enrolled":55,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07357519/"}
{"id":"nct07432633","kind":"trial","name":"[18F]FPyQCP PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications","aka":[],"tldr":"A phase 1/2 trial of [18F]FPyQCP in colorectal cancer, ovarian cancer, gastric & gastro-oesophageal junction cancer and pancreatic ductal adenocarcinoma, run by Blue Earth Diagnostics, now recruiting.","summary":"[18F]FPyQCP PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications is a phase 1/2 interventional study registered as NCT07432633 by Blue Earth Diagnostics, with 71 participants planned, started 2026-02-19 and due to reach its primary completion in 2028-01-31. Interventions recorded: [18F]FPyQCP.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07432633","url":"https://clinicaltrials.gov/study/NCT07432633"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["blue-earth-diagnostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07432633","phase":"1/2","setting":"A Phase 1/2 Study of [18F]FPyQCP for PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications","sponsor":"Blue Earth Diagnostics","enrolled":71,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07432633/"}
{"id":"nct07567521","kind":"trial","name":"A Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive mCRPC","aka":[],"tldr":"A phase 1/2 trial of Radiopharmaceuticals in prostate cancer, run by C Ray Therapeutics, now recruiting.","summary":"A Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive mCRPC is a phase 1/2 interventional study registered as NCT07567521 by C Ray Therapeutics, with 90 participants planned, started 2026-05-22 and due to reach its primary completion in 2027-12-30. Interventions recorded: Radiopharmaceuticals.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07567521","url":"https://clinicaltrials.gov/study/NCT07567521"}],"tags":["pipeline","ctgov-ingest"],"related":[],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07567521","phase":"1/2","setting":"A Prospective, Open-label, Randomized, Phase 1/2 Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)","sponsor":"C Ray Therapeutics","enrolled":90,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07567521/"}
{"id":"nct07590934","kind":"trial","name":"Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer","aka":["PROSPECTOR"],"tldr":"A phase 1/2 trial of FPI-2265, Actinium-225 PSMA agents, Palacaparib in prostate cancer, run by AstraZeneca, now recruiting.","summary":"Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer is a phase 1/2 interventional study registered as NCT07590934 by AstraZeneca, with 152 participants planned, started 2026-06-03 and due to reach its primary completion in 2029-09-25. Interventions recorded: AZD2265 (FPI-2265), Palacaparib (AZD9574), Docetaxel, AZD2287 (Imaging agent). Conditions listed: Metastatic Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07590934","url":"https://clinicaltrials.gov/study/NCT07590934"}],"tags":["ctgov-ingest"],"related":["ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["fpi-2265","ac225-psma","docetaxel"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07590934","phase":"1/2","setting":"A Phase Ib/II, Open-label, Multi-centre, Platform Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Multiple Anti-Cancer Agents in Metastatic Prostate Cancer","sponsor":"AstraZeneca","enrolled":152,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07590934/"}
{"id":"nct07611110","kind":"trial","name":"AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)","aka":["VECTRA-01"],"tldr":"A phase 3 trial of FPI-2265, Cabazitaxel, Abiraterone acetate in prostate cancer, run by AstraZeneca, now recruiting.","summary":"AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01) is a phase 3 interventional study registered as NCT07611110 by AstraZeneca, with 670 participants planned, started 2026-05-04 and due to reach its primary completion in 2029-06-04. Interventions recorded: Actinium (225Ac) zadavotide guraxetan (AZD2265 [FPI-2265]), Cabazitaxel, Abiraterone, Enzalutamide, Apalutamide. Conditions listed: Metastatic Castration-resistant Prostate Cancer. No results are recorded here; the registry entry is the source.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07611110","url":"https://clinicaltrials.gov/study/NCT07611110"}],"tags":["ctgov-ingest"],"related":["ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["fpi-2265","cabazitaxel","abiraterone","enzalutamide"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07611110","phase":"3","setting":"A Phase III, Multicentre, Randomised Controlled Study to Evaluate the Efficacy and Safety of AZD2265 (FPI-2265) ²²⁵Ac-PSMA-I&T Compared With Standard of Care in Patients With PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)","sponsor":"AstraZeneca","enrolled":670,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07611110/"}
{"id":"nct07615101","kind":"trial","name":"Investigating the Safety and Diagnostic Performance of 68Ga-NYM032 Injection PET/CT in Men With Newly Diagnosed Prostate Cancer.","aka":[],"tldr":"A phase 3 trial of 68-Ga-NYM032 in prostate cancer, run by Norroy Bioscience Co., LTD, now recruiting.","summary":"Investigating the Safety and Diagnostic Performance of 68Ga-NYM032 Injection PET/CT in Men With Newly Diagnosed Prostate Cancer. is a phase 3 interventional study registered as NCT07615101 by Norroy Bioscience Co., LTD, with 365 participants planned, started 2026-08-06 and due to reach its primary completion in 2027-06-30. Interventions recorded: 68-Ga-NYM032.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07615101","url":"https://clinicaltrials.gov/study/NCT07615101"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68"],"indications":["prostate"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07615101","phase":"3","setting":"Open-label, Phase 3, Multi Center, Single-arm, Imaging Study Investigating the Safety and Diagnostic Performance of 68Ga-NYM032 Injection PET/CT in Men With Newly Diagnosed Prostate Cancer.","sponsor":"Norroy Bioscience Co., LTD","enrolled":365,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07615101/"}
{"id":"nct07649122","kind":"trial","name":"This Study Evaluates the Diagnostic Performance and Safety of 68Ga-NYM032 PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer.","aka":[],"tldr":"A phase 3 trial of an investigational treatment in prostate cancer, run by Norroy Bioscience Co., LTD, now recruiting.","summary":"This Study Evaluates the Diagnostic Performance and Safety of 68Ga-NYM032 PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer. is a phase 3 interventional study registered as NCT07649122 by Norroy Bioscience Co., LTD, with 232 participants planned, started 2026-08-31 and due to reach its primary completion in 2028-06-30.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07649122","url":"https://clinicaltrials.gov/study/NCT07649122"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68"],"indications":["prostate"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07649122","phase":"3","setting":"A Phase 3, Multi-Center, Open-Label Study to Assess the Diagnostic Performance and Safety of 68Ga-NYM032 Injection PET/CT Imaging Results in Men With Suspected Recurrence of Prostate Cancer","sponsor":"Norroy Bioscience Co., LTD","enrolled":232,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07649122/"}
{"id":"nct07691775","kind":"trial","name":"A Study to Evaluate the Safety and Diagnostic Performance of F18 FBPA PET/CT Imaging in Solid Tumors","aka":[],"tldr":"A phase 1/2 trial of F18 FBPA Injection in advanced solid tumours, run by Heron Neutron Medical Corp., now recruiting.","summary":"A Study to Evaluate the Safety and Diagnostic Performance of F18 FBPA PET/CT Imaging in Solid Tumors is a phase 1/2 interventional study registered as NCT07691775 by Heron Neutron Medical Corp., with 30 participants planned, started 2026-05-20 and due to reach its primary completion in 2026-12. Interventions recorded: F18 FBPA Injection.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07691775","url":"https://clinicaltrials.gov/study/NCT07691775"}],"tags":["pipeline","ctgov-ingest"],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07691775","phase":"1/2","setting":"A Study to Evaluate the Safety and Diagnostic Performance of F18 FBPA PET/CT Imaging in Solid Tumors","sponsor":"Heron Neutron Medical Corp.","enrolled":30,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07691775/"}
{"id":"nct07702292","kind":"trial","name":"[68Ga]BED003 PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications","aka":[],"tldr":"A phase 2 trial of [68Ga]BED003 in colorectal cancer, ovarian cancer, gastric & gastro-oesophageal junction cancer and pancreatic ductal adenocarcinoma, run by Blue Earth Diagnostics, now recruiting.","summary":"[68Ga]BED003 PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications is a phase 2 interventional study registered as NCT07702292 by Blue Earth Diagnostics, with 71 participants planned, started 2026-06-30 and due to reach its primary completion in 2028-02. Interventions recorded: [68Ga]BED003.","status":"recruiting","asOf":"2026-09-16","links":[{"label":"ClinicalTrials.gov NCT07702292","url":"https://clinicaltrials.gov/study/NCT07702292"}],"tags":["pipeline","ctgov-ingest"],"related":["ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["blue-earth-diagnostics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT07702292","phase":"2","setting":"A Phase 2 Study of [68Ga]BED003 for PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications","sponsor":"Blue Earth Diagnostics","enrolled":71,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct07702292/"}
{"id":"netter-1","kind":"trial","name":"NETTER-1","aka":[],"tldr":"The trial that made radioligand therapy a standard: a radioactive drug homing to the somatostatin receptor held midgut neuroendocrine tumours in check far longer than high-dose octreotide, and it underpins Lutathera's approvals.","summary":"NETTER-1, trial NCT01578239 sponsored by Advanced Accelerator Applications and published in the New England Journal of Medicine in 2017, randomised 231 patients with inoperable, progressive, somatostatin receptor-positive midgut neuroendocrine tumours to 177Lu-Dotatate (four cycles, with octreotide) or high-dose octreotide LAR. Progression-free survival at 20 months was 65.2% with 177Lu-Dotatate against 10.8% with octreotide, and the response rate was 18% against 3%. The result supported the 2018 US and EU approvals of Lutathera and made peptide receptor radionuclide therapy the reference treatment after somatostatin analogues.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT01578239","url":"https://clinicaltrials.gov/study/NCT01578239"},{"label":"Strosberg et al., Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumours (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1607427"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine","small-intestinal-net"],"sections":[],"technologies":["prrt"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01578239","phase":"3","setting":"Inoperable, progressive midgut neuroendocrine tumours: 177Lu-Dotatate plus octreotide versus high-dose octreotide LAR","sponsor":"Advanced Accelerator Applications (Novartis)","result":"PFS at 20 months 65.2% vs 10.8% (HR 0.21); ORR 18% vs 3%.","yearReported":2017,"enrolled":231,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 20 months","primary":true,"unit":"%","arms":[{"name":"177Lu-Dotatate + octreotide","n":116,"value":65.2},{"name":"High-dose octreotide LAR","n":113,"value":10.8}],"hr":0.21,"ci":[0.13,0.33],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa1607427"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"177Lu-Dotatate + octreotide","n":116,"value":18},{"name":"High-dose octreotide LAR","n":113,"value":3}],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa1607427"}],"route":"/trials/netter-1/"}
{"id":"phergain","kind":"trial","name":"PHERGain","aka":[],"tldr":"Using an early PET scan to spot responders let a third of women be cured of HER2-positive breast cancer without any chemotherapy.","summary":"PET responders after 2 cycles continued antibodies alone; those achieving pCR (37.9% of the arm) skipped chemotherapy entirely. 3-year iDFS 95.4% in the PET-adapted arm, meeting its co-primary endpoint. Discussed at ESMO Breast 2026 as the model for imaging-guided de-escalation; a phase 3 (PHERGain-2) is underway.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03161353","url":"https://clinicaltrials.gov/study/NCT03161353"}],"tags":[],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":["fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03161353","phase":"2","setting":"HER2+ early breast cancer: chemotherapy-free trastuzumab + pertuzumab with early 18F-FDG PET response assessment to decide whether chemotherapy is needed","sponsor":"MEDSIR","result":"3-year iDFS 95.4% in the PET-adapted arm; ~1 in 3 spared chemotherapy.","yearReported":2024,"enrolled":377,"enrolledBasis":"registry","outcomes":[{"endpoint":"3-year invasive disease-free survival (PET-adapted arm)","primary":true,"unit":"%","arms":[{"name":"PET-adapted HP ± chemotherapy","n":285,"value":95.4}],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00054-0/fulltext"}],"replication":"Consistent with WSG-ADAPT HER2+/HR- (pCR-guided de-escalation); phase 3 confirmation pending.","route":"/trials/phergain/"}
{"id":"pop-rt","kind":"trial","name":"POP-RT","aka":[],"tldr":"POP-RT, from Mumbai, showed that treating the pelvic lymph nodes as well as the prostate improves disease control in high-risk prostate cancer, reviving a question earlier trials had left unanswered.","summary":"POP-RT randomised 224 men with high-risk, node-negative prostate cancer (most staged with PSMA PET) to image-guided prostate-only or whole-pelvic radiotherapy with two years of androgen deprivation. Five-year biochemical failure-free survival was 95 percent with pelvic radiotherapy and 81.2 percent with prostate-only treatment (hazard ratio 0.23), with better disease-free survival and more late urinary toxicity (Murthy and colleagues, Journal of Clinical Oncology 2021).","status":"positive","asOf":"2026-09-27","links":[{"label":"ClinicalTrials.gov NCT02302105 (POP-RT, Tata Memorial Centre)","url":"https://clinicaltrials.gov/study/NCT02302105"},{"label":"JCO 2021","url":"https://doi.org/10.1200/JCO.20.03282"}],"tags":["radiation-wave4"],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02302105","phase":"3","setting":"High-risk node-negative prostate cancer: prostate-only versus whole-pelvic radiotherapy, both with hormone therapy","sponsor":"Tata Memorial Centre, Mumbai","result":"5-year biochemical failure-free survival 95% (whole pelvis) vs 81.2% (prostate only).","yearReported":2021,"enrolled":224,"enrolledBasis":"registry","outcomes":[{"endpoint":"Biochemical failure-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Whole-pelvic radiotherapy","n":110,"value":95},{"name":"Prostate-only radiotherapy","n":114,"value":81.2}]}],"route":"/trials/pop-rt/"}
{"id":"propsma","kind":"trial","name":"proPSMA","aka":[],"tldr":"Proved PSMA PET is far more accurate than conventional scans for staging, with less radiation.","summary":"proPSMA, registered as ANZCTR12617000005358, sponsored by Peter MacCallum Cancer Centre and ANZUP and reported in the Lancet in 2020, proved that PSMA PET/CT is far more accurate than CT plus bone scan for staging high-risk localised prostate cancer, with less radiation. It randomised 302 men, found an accuracy of 92 percent for PSMA PET against 65 percent for conventional imaging, produced fewer equivocal findings and changed management more often. Nuclide links it to PSMA PET, Peter MacCallum, ANZUP, Michael Hofman, Ian Davis and Declan G. Murphy, and its findings are consistent with the OSPREY and CONDOR studies for the fluorine-18 tracer DCFPyL. Whether better staging translates into better outcomes, rather than only different decisions, is the open question that follows any diagnostic accuracy trial. PSMA PET has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"Lancet 2020","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30314-7/fulltext"}],"tags":[],"related":["f-18"],"indications":["prostate","prostate-high-risk"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":["peter-mac"],"pathways":[],"terms":[],"trials":[],"people":["declan-murphy","hofman-michael"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"ANZCTR12617000005358","phase":"3","setting":"High-risk localised prostate cancer staging: PSMA PET/CT vs CT + bone scan","sponsor":"Peter MacCallum Cancer Centre / ANZUP","result":"Accuracy 92% vs 65%.","yearReported":2020,"enrolled":302,"enrolledBasis":"registry","outcomes":[{"endpoint":"Accuracy for pelvic nodal or distant metastases (AUC)","primary":true,"unit":"%","arms":[{"name":"PSMA PET/CT","n":150,"value":92},{"name":"CT + bone scan","n":152,"value":65}],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30314-7/fulltext"}],"replication":"Consistent with the OSPREY and CONDOR registrational studies for 18F-DCFPyL.","route":"/trials/propsma/"}
{"id":"prosper","kind":"trial","name":"PROSPER","aka":[],"tldr":"PROSPER showed that enzalutamide delayed the appearance of metastases by about two years, and later helped men live longer, when given at the point where prostate cancer is rising on hormone therapy but has not yet spread on scans.","summary":"PROSPER randomised 1401 men with castration-resistant prostate cancer, no metastases on conventional imaging and a PSA doubling time of ten months or less two to one to enzalutamide or placebo alongside androgen deprivation. The primary endpoint was metastasis-free survival.\n\nEnzalutamide lengthened metastasis-free survival substantially and delayed the time to PSA progression and to further antineoplastic therapy; with longer follow-up overall survival was also improved. Fatigue, hypertension and falls were the main added toxicities. It was approved for this indication in July 2018 and, with SPARTAN (apalutamide) and ARAMIS (darolutamide), defined androgen receptor pathway inhibition as the standard for high-risk non-metastatic castration-resistant disease, a group that PSMA PET imaging has since shrunk.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02003924","url":"https://clinicaltrials.gov/study/NCT02003924"}],"tags":["subtype-trials"],"related":[],"indications":["prostate-nmcrpc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["enzalutamide"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02003924","phase":"3","setting":"Non-metastatic castration-resistant prostate cancer with a PSA doubling time of ten months or less: enzalutamide against placebo, both with continued androgen deprivation","sponsor":"Pfizer (Medivation) and Astellas","result":"Enzalutamide lengthened metastasis-free survival and, with longer follow-up, overall survival compared with placebo; approved in July 2018.","yearReported":2018,"enrolled":1401,"enrolledBasis":"registry","outcomes":[{"endpoint":"Metastasis-free survival","primary":true,"unit":"months","arms":[{"name":"Enzalutamide","n":933,"value":36.6},{"name":"Placebo","n":468,"value":14.7}],"hr":0.29,"ci":[0.24,0.35],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa1800536"},{"endpoint":"Time to PSA progression","unit":"months","arms":[{"name":"Enzalutamide","n":933,"value":37.2},{"name":"Placebo","n":468,"value":3.9}],"hr":0.07,"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa1800536"},{"endpoint":"Time to first subsequent antineoplastic therapy","unit":"months","arms":[{"name":"Enzalutamide","n":933,"value":39.6},{"name":"Placebo","n":468,"value":17.7}],"hr":0.21,"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa1800536"},{"endpoint":"Grade 3 or higher adverse events","unit":"%","arms":[{"name":"Enzalutamide","value":31},{"name":"Placebo","value":23}],"source":"https://doi.org/10.1056/NEJMoa1800536"}],"route":"/trials/prosper/"}
{"id":"psmaddition","kind":"trial","name":"PSMAddition","aka":[],"tldr":"PSMAddition moved the radioligand Pluvicto into the first treatment of metastatic hormone-sensitive prostate cancer, given alongside hormone therapy, and the FDA approved this use on 31 July 2026. It delayed progression on scans, but severe side effects were more common and whether it lengthens life is not yet known.","summary":"PSMAddition, trial NCT04720157 sponsored by Novartis and reported in 2025, moved Pluvicto, or 177Lu-PSMA-617, into the first-line treatment of metastatic prostate cancer, and the FDA approved this use on 31 July 2026. It randomised 1,144 men with PSMA-positive metastatic hormone-sensitive disease to the radioligand plus androgen deprivation and an androgen receptor pathway inhibitor or to standard care alone, and met its primary radiographic progression-free survival endpoint at ESMO 2025 with a stronger effect at update, while overall survival trended favourably but remained immature and severe adverse events were more common. Nuclide links it to radioligand therapy, the CRPC term and the idea of alpha-emitting PSMA therapy at first diagnosis. Whether early radioligand use improves survival or only delays progression is the open question.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04720157","url":"https://clinicaltrials.gov/study/NCT04720157"},{"label":"FDA approval 31 Jul 2026","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy"},{"label":"Annals of Oncology LBA6 (ESMO 2025)","url":"https://www.annalsofoncology.org/article/S0923-7534(25)04871-9/fulltext"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mhspc"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04720157","phase":"3","setting":"PSMA-positive metastatic hormone-sensitive prostate cancer: 177Lu-PSMA-617 + ADT + ARPI vs ADT + ARPI","sponsor":"Novartis","result":"rPFS HR 0.72 (updated 0.67); OS HR 0.80 (NS, immature).","yearReported":2025,"enrolled":1144,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care (ARPI + ADT)","note":"Updated HR 0.67; OS HR 0.80, immature"},{"name":"Standard care"}],"hr":0.72,"ci":[0.58,0.89],"p":"0.0016","source":"https://clinicaltrials.gov/study/NCT04720157"}],"replication":"Extends VISION and PSMAfore into hormone-sensitive disease; supported the July 2026 label expansion.","route":"/trials/psmaddition/"}
{"id":"psmafore","kind":"trial","name":"PSMAfore","aka":[],"tldr":"PSMAfore moved Pluvicto before chemotherapy in prostate cancer.","summary":"PSMAfore, trial NCT04689828 sponsored by Novartis and published in the Lancet in 2024, moved Pluvicto, or 177Lu-PSMA-617, before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer after one androgen receptor pathway inhibitor. It randomised 468 taxane-naive men to the radioligand or a switch of androgen receptor pathway inhibitor, met its primary radiographic progression-free survival endpoint with a large effect, and overall survival was confounded by crossover of most control patients, with crossover-adjusted analyses favouring the radioligand; approval in the pre-chemotherapy setting followed in 2025. Whether earlier use improves survival, not just progression, is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04689828","url":"https://clinicaltrials.gov/study/NCT04689828"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oliver-sartor","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04689828","phase":"3","setting":"PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch","sponsor":"Novartis","result":"rPFS HR 0.41.","yearReported":2023,"enrolled":469,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617","n":234,"value":12},{"name":"ARPI switch","n":234,"value":5.6}],"hr":0.41,"ci":[0.29,0.56],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"},{"endpoint":"Overall survival (crossover-adjusted)","unit":"months","arms":[{"name":"177Lu-PSMA-617","note":"Unadjusted OS HR 0.98 with 84% crossover from control"},{"name":"ARPI switch"}],"hr":0.59,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"}],"replication":"Confirms VISION in the pre-chemotherapy line; SPLASH (177Lu-PSMA-I&T) showed a smaller rPFS effect and no OS benefit, so agent and setting details matter.","route":"/trials/psmafore/"}
{"id":"radiant-3-4","kind":"trial","name":"RADIANT-3 and RADIANT-4","aka":[],"tldr":"The two trials that made everolimus a standard pill for pancreatic, lung and gut neuroendocrine tumours.","summary":"RADIANT-3 and RADIANT-4, led by trial NCT00510068 and sponsored by Novartis, are the two trials, reported from 2011, that made everolimus a standard tablet for pancreatic, lung and gastrointestinal neuroendocrine tumours. RADIANT-3 randomised 410 patients with progressive pancreatic neuroendocrine tumours and RADIANT-4 302 patients with lung or gastrointestinal tumours to everolimus or placebo, and both met their primary progression-free survival endpoints with large effects, while overall survival was not significantly improved because of crossover. Nuclide links them to neuroendocrine tumours, everolimus and James C. Yao. Whether everolimus should come before or after radioligand therapy, which COMPETE has now tested directly, is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00510068","url":"https://clinicaltrials.gov/study/NCT00510068"}],"tags":[],"related":[],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net","lung-net"],"sections":[],"technologies":[],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00510068","phase":"3","setting":"Progressive pancreatic NETs (RADIANT-3, n=410) and lung/GI NETs (RADIANT-4, n=302): everolimus vs placebo","sponsor":"Novartis","result":"PFS HR 0.35 (pNET) and 0.48 (lung/GI).","yearReported":2011,"enrolled":712,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (RADIANT-3)","primary":true,"unit":"months","arms":[{"name":"Everolimus","n":207,"value":11},{"name":"Placebo","n":203,"value":4.6}],"hr":0.35,"ci":[0.27,0.45],"source":"https://doi.org/10.1056/NEJMoa1009290"},{"endpoint":"Progression-free survival (RADIANT-4)","primary":true,"unit":"months","arms":[{"name":"Everolimus","n":205,"value":11},{"name":"Placebo","n":97,"value":3.9}],"hr":0.48,"ci":[0.35,0.67],"source":"https://doi.org/10.1016/S0140-6736(15)00817-X"}],"route":"/trials/radiant-3-4/"}
{"id":"rathl","kind":"trial","name":"RATHL","aka":[],"tldr":"Showed that patients whose PET scan is clear after two cycles can safely drop bleomycin and its lung toxicity.","summary":"RATHL, trial NCT00678327 sponsored by the UK NCRI and Cancer Research UK and published in the New England Journal of Medicine in 2016, showed that patients with advanced Hodgkin lymphoma whose PET scan is clear after two cycles can safely drop bleomycin and its lung toxicity. It enrolled 1,214 patients, randomised those with a negative interim PET to continue ABVD or switch to AVD, met its non-inferiority endpoint on progression-free survival with fewer pulmonary events, and escalated PET-positive patients to BEACOPP. Nuclide links it to Hodgkin lymphoma, PET-adapted therapy, FDG PET, the Deauville scale term, Cancer Research UK, Peter Johnson and the bleomycin caution pairing, and it is concordant with GHSG HD18. It established interim PET as a treatment-steering tool, and whether PET can guide even deeper de-escalation is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00678327","url":"https://clinicaltrials.gov/study/NCT00678327"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-adapted-therapy","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00678327","phase":"3","setting":"Advanced Hodgkin lymphoma: interim-PET-guided omission of bleomycin (AVD) vs continued ABVD","sponsor":"UK NCRI / Cancer Research UK","result":"3-year PFS 85.7% (ABVD) vs 84.4% (AVD); bleomycin safely omitted.","yearReported":2016,"enrolled":1214,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 3 years (PET2-negative)","primary":true,"unit":"%","arms":[{"name":"ABVD","n":470,"value":85.7},{"name":"AVD","n":465,"value":84.4}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1510093"}],"replication":"Concordant with GHSG HD18 (shortened BEACOPP after negative PET2).","route":"/trials/rathl/"}
{"id":"sarah-sirvenib","kind":"trial","name":"SARAH and SIRveNIB","aka":[],"tldr":"Two large trials found radioactive beads were gentler than sorafenib but did not help patients live longer.","summary":"SARAH and SIRveNIB, led by trial NCT01482442 and sponsored by AP-HP and the National Cancer Centre Singapore, were two large trials reported in 2017 that found yttrium-90 radioembolisation was gentler than sorafenib in locally advanced hepatocellular carcinoma but did not help patients live longer. SARAH randomised 459 patients and SIRveNIB 360, and neither improved overall survival, although the radioactive beads gave better quality of life and more responses. Nuclide links them to hepatocellular carcinoma, radioembolisation and sorafenib. The results were interpreted as showing the need for personalised dosimetry and earlier-stage use rather than the failure of the modality, and whether dosimetry-guided radioembolisation can succeed where fixed dosing did not is the open question.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01482442","url":"https://clinicaltrials.gov/study/NCT01482442"}],"tags":["failure","lesson:patient-selection"],"related":["y-90"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01482442","phase":"3","setting":"Locally advanced HCC: yttrium-90 radioembolisation vs sorafenib","sponsor":"AP-HP (SARAH); NCC Singapore (SIRveNIB)","result":"OS not improved; fewer adverse events.","yearReported":2017,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival (SARAH)","primary":true,"unit":"months","arms":[{"name":"Y-90 SIRT","n":237,"value":8},{"name":"Sorafenib","n":222,"value":9.9}],"hr":1.15,"source":"https://doi.org/10.1016/S1470-2045(17)30683-6"}],"route":"/trials/sarah-sirvenib/"}
{"id":"select-lenvatinib","kind":"trial","name":"SELECT","aka":[],"tldr":"Turned lenvatinib into the main drug for thyroid cancers that no longer take up radioactive iodine, quadrupling the time before the disease grew.","summary":"SELECT, trial NCT01321554 sponsored by Eisai and reported in 2015, turned lenvatinib into the main drug for differentiated thyroid cancers that no longer take up radioactive iodine, quadrupling the time before the disease grew. It randomised 392 patients with progressive radioiodine-refractory disease to lenvatinib or placebo, met its primary progression-free survival endpoint with a very large effect and a response rate near two-thirds against almost none on placebo, leading to FDA approval in February 2015; hypertension in about two-thirds and dose reductions in more than sixty percent drive management, and survival was confounded by crossover. Nuclide links it to thyroid cancer, kinase inhibitors and anti-angiogenic therapy, VEGF and RET as targets, the radioiodine-refractory term and Martin Schlumberger. When to start a drug this toxic in a slow disease is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01321554","url":"https://clinicaltrials.gov/study/NCT01321554"},{"label":"NEJM 2015","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1406470"}],"tags":[],"related":[],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01321554","phase":"3","setting":"Radioiodine-refractory differentiated thyroid cancer with progression: lenvatinib vs placebo","sponsor":"Eisai","result":"PFS 18.3 vs 3.6 months; HR 0.21.","yearReported":2015,"enrolled":392,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Lenvatinib","value":18.3},{"name":"Placebo","value":3.6}],"hr":0.21,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1406470"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Lenvatinib","value":64.8},{"name":"Placebo","value":1.5}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1406470"}],"replication":"DECISION (sorafenib) showed the same direction with a smaller effect; class effect of VEGFR multikinase inhibitors is established.","route":"/trials/select-lenvatinib/"}
{"id":"splash","kind":"trial","name":"SPLASH","aka":[],"tldr":"In SPLASH, a second PSMA radioligand improved progression-free survival but not, so far, survival.","summary":"SPLASH, trial NCT04647526 sponsored by Lantheus through POINT Biopharma and reported in 2024, tested a second PSMA radioligand, 177Lu-PNT2002, also known as 177Lu-PSMA-I&T, against a switch of androgen receptor pathway inhibitor in PSMA-positive, taxane-naive metastatic castration-resistant prostate cancer. It randomised 412 men and met its primary radiographic progression-free survival endpoint, but the interim overall survival analysis was numerically unfavourable, with 46 percent of events and 84 percent crossover, and Lantheus deprioritised a US filing pending mature data. Nuclide links it to prostate cancer and to the 177Lu-PSMA-I&T drug record; its effect was smaller than PSMAfore's with a different ligand and dosing, while ECLIPSE with the same ligand met its progression endpoint. Whether crossover masked a real benefit or the drug simply adds little is the open question.","status":"mixed","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04647526","url":"https://clinicaltrials.gov/study/NCT04647526"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["lu177-psma-it"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04647526","phase":"3","setting":"PSMA-positive mCRPC after one ARPI, taxane-naive: 177Lu-PNT2002 vs ARPI switch","sponsor":"Lantheus (POINT Biopharma)","result":"rPFS HR 0.71; interim OS HR 1.11.","yearReported":2024,"enrolled":455,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PNT2002 (PSMA-I&T)","n":276,"value":9.5},{"name":"ARPI switch","n":136,"value":6}],"hr":0.71,"ci":[0.55,0.92],"p":"0.0088","source":"https://clinicaltrials.gov/study/NCT04647526"},{"endpoint":"Overall survival (interim)","unit":"months","arms":[{"name":"177Lu-PNT2002","note":"Numerically unfavourable at interim with crossover"},{"name":"ARPI switch"}],"hr":1.11,"source":"https://clinicaltrials.gov/study/NCT04647526"}],"replication":"Smaller effect than PSMAfore (rPFS HR 0.41) with a different ligand and dosing; ECLIPSE (177Lu-PSMA-I&T) met rPFS.","route":"/trials/splash/"}
{"id":"stampede","kind":"trial","name":"STAMPEDE","aka":["STAMPEDE trial","MRC PR08","Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy","STAMPEDE platform"],"tldr":"STAMPEDE is the longest-running platform trial in oncology, and showed that both docetaxel and abiraterone extend life when started at first diagnosis of metastatic disease.","summary":"STAMPEDE opened in 2005 at the MRC Clinical Trials Unit at UCL, with Nicholas James as chief investigator and Mahesh Parmar as its statistician, as the first multi-arm multi-stage trial in cancer: several experimental arms recruited at once against one control arm of androgen deprivation therapy, each passing through interim activity stages before being allowed to continue to an overall survival comparison, with new arms added and failing arms dropped as the standard of care moved. Nearly 12,000 men with high-risk locally advanced or newly metastatic prostate cancer joined at more than 100 hospitals in the United Kingdom and Switzerland; Silke Gillessen led the Swiss contribution and later co-chaired the trial. The original arms added zoledronic acid, docetaxel, celecoxib and their combinations; the celecoxib arms were stopped for lack of activity in 2011, and abiraterone (2011), radiotherapy to the prostate (2013), abiraterone with enzalutamide (2014), metformin (2016) and transdermal oestradiol (run jointly with the PATCH trial) were added.\n\nThe results arrived in sequence and each changed practice. In 2016 the Lancet reported that docetaxel added to hormone therapy improved overall survival, most clearly in metastatic disease, while zoledronic acid added nothing; the finding replicated CHAARTED and made early chemotherapy a standard. In 2017 the New England Journal of Medicine reported, alongside LATITUDE, that abiraterone with prednisolone cut the risk of death by about a third (hazard ratio 0.63), which established abiraterone at first diagnosis of metastatic disease. In 2018 the Lancet reported that radiotherapy to the prostate improved survival in men with a low metastatic burden but not overall, and low-volume prostate radiotherapy entered guidelines. In 2022 the Lancet reported that two years of abiraterone improved metastasis-free and overall survival in high-risk non-metastatic disease, and that adding enzalutamide brought toxicity without benefit; the Lancet Oncology in 2023 confirmed the same for enzalutamide in metastatic disease. The metformin comparison, reported at ESMO in 2024 and since published, found no overall survival benefit from adding metformin for men starting hormone therapy for metastatic disease. The transdermal oestradiol comparison, run with PATCH, showed that oestrogen patches suppress testosterone as well as injections with fewer hot flushes, better bone health and no excess of cardiovascular events (Lancet 2021).\n\nSTAMPEDE is the proof that a single academic platform with a shared control arm can answer a decade of questions faster and more cheaply than separate trials, and its multi-arm multi-stage design is now used across cancer and beyond. Its weaknesses are the ones every platform inherits: the control arm changed as docetaxel and then abiraterone became standard, so later arms were compared with a moving baseline, and some comparisons (radiotherapy, enzalutamide) were read in subgroups defined after the fact. The successor, STAMPEDE2, opened in 2023 with comparisons of stereotactic radiotherapy to metastases, lutetium PSMA radioligand therapy and niraparib with abiraterone in men starting treatment for metastatic disease.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT00268476","url":"https://clinicaltrials.gov/study/NCT00268476"},{"label":"James et al., Lancet 2016: addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(15)01037-5"},{"label":"James et al., NEJM 2017: abiraterone for prostate cancer not previously treated with hormone therapy (STAMPEDE)","url":"https://doi.org/10.1056/NEJMoa1702900"},{"label":"Parker et al., Lancet 2018: radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(18)32486-3"},{"label":"Attard et al., Lancet 2022: abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(21)02437-5"},{"label":"Attard et al., Lancet Oncology 2023: abiraterone plus prednisolone with or without enzalutamide for metastatic prostate cancer starting ADT (STAMPEDE)","url":"https://doi.org/10.1016/S1470-2045(23)00148-1"},{"label":"Langley et al., Lancet 2021: transdermal oestradiol for androgen suppression in prostate cancer, long-term cardiovascular outcomes from PATCH","url":"https://doi.org/10.1016/S0140-6736(21)00100-8"},{"label":"STAMPEDE trial website (MRC CTU at UCL)","url":"https://www.stampedetrial.org"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","docetaxel","enzalutamide"],"companies":[],"institutions":["royal-marsden"],"pathways":[],"terms":["mcrpc-mhspc"],"trials":[],"people":["silke-gillessen"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00268476","phase":"platform","setting":"Multi-arm multi-stage platform in men starting long-term hormone therapy for high-risk locally advanced or metastatic prostate cancer: docetaxel, zoledronic acid, celecoxib, abiraterone, radiotherapy to the prostate, abiraterone with enzalutamide, metformin and transdermal oestradiol added to ADT and compared with ADT alone","sponsor":"MRC Clinical Trials Unit at UCL, funded by Cancer Research UK and the Medical Research Council","result":"Abiraterone + ADT: OS HR 0.63 in mHSPC; docetaxel + ADT: OS HR 0.78. Prostate radiotherapy improved survival in low-volume metastatic disease; abiraterone improved survival in high-risk non-metastatic disease; enzalutamide added to abiraterone, zoledronic acid, celecoxib and metformin did not improve survival.","yearReported":2016,"enrolled":11992,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, abiraterone arm (M1 subgroup)","primary":true,"unit":"%","arms":[{"name":"ADT + abiraterone","note":"6-year OS 60%"},{"name":"ADT alone","note":"6-year OS 45%"}],"hr":0.6,"ci":[0.5,0.71],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00367-1/fulltext"},{"endpoint":"Overall survival, docetaxel arm (M1)","unit":"months","arms":[{"name":"ADT + docetaxel","value":60},{"name":"ADT alone","value":45}],"hr":0.76,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01037-5/fulltext"}],"replication":"Abiraterone result replicated by LATITUDE; docetaxel result replicated by CHAARTED.","route":"/trials/stampede/"}
{"id":"therap","kind":"trial","name":"TheraP (ANZUP 1603)","aka":[],"tldr":"The randomised trial that first pitted a radioligand against chemotherapy and won on response, with fewer side effects.","summary":"TheraP, ANZUP trial 1603, NCT03392428, sponsored by ANZUP and Peter MacCallum and reported in 2021, was the randomised phase 2 that first pitted a radioligand against chemotherapy, comparing 177Lu-PSMA-617 with cabazitaxel in metastatic castration-resistant prostate cancer after docetaxel, with patients selected by PSMA and FDG PET. It randomised 200 men, met its primary endpoint with a PSA response of at least fifty percent in 66 percent of men against 37 percent, delayed progression and gave better quality of life with fewer side effects, but overall survival was similar in the 2024 analysis after crossover. Nuclide links it to radioligand therapy, PSMA PET, lutetium-177 vipivotide tetraxetan, cabazitaxel, Michael Hofman and the PSA50 term, and it is consistent with VISION on activity. The survival equivalence with cabazitaxel is the nuance that matters for sequencing, which remains open.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT03392428","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":["pluvicto","cabazitaxel"],"companies":[],"institutions":["peter-mac"],"pathways":[],"terms":["psa50"],"trials":[],"people":["hofman-michael"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03392428","phase":"2","setting":"mCRPC after docetaxel: 177Lu-PSMA-617 vs cabazitaxel, PSMA PET/FDG PET selected","sponsor":"ANZUP / Peter MacCallum","result":"PSA50 66% vs 37%; OS HR 0.97.","yearReported":2021,"enrolled":201,"enrolledBasis":"registry","outcomes":[{"endpoint":"PSA response ≥50%","primary":true,"unit":"%","arms":[{"name":"177Lu-PSMA-617","n":99,"value":66},{"name":"Cabazitaxel","n":101,"value":37}],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00237-3/fulltext"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"177Lu-PSMA-617","value":19.1,"note":"Not different"},{"name":"Cabazitaxel","value":19.6}],"hr":0.97,"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00529-6/fulltext"}],"replication":"Consistent with VISION on activity; the OS equivalence with cabazitaxel is an important nuance for sequencing.","route":"/trials/therap/"}
{"id":"vision","kind":"trial","name":"VISION","aka":[],"tldr":"VISION was the trial that established radioligand therapy in prostate cancer.","summary":"VISION, trial NCT03511664 sponsored by Novartis and published in the New England Journal of Medicine in 2021, was the trial that established radioligand therapy in prostate cancer. It randomised 831 men with PSMA-positive metastatic castration-resistant prostate cancer after an androgen receptor pathway inhibitor and a taxane to 177Lu-PSMA-617 plus standard care or standard care alone, selected by PSMA PET, and met both primary endpoints of overall and radiographic progression-free survival. Whether radioligand therapy should now be given before chemotherapy or even at diagnosis, as PSMAfore and PSMAddition test, is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03511664","url":"https://clinicaltrials.gov/study/NCT03511664"}],"tags":[],"related":["lu-177"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oliver-sartor","ken-herrmann","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03511664","phase":"3","setting":"PSMA+ metastatic castration-resistant prostate cancer after ARPI and taxane: 177Lu-PSMA-617 + SOC vs SOC","sponsor":"Novartis","result":"OS HR 0.62.","yearReported":2021,"enrolled":861,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care","n":551,"value":15.3},{"name":"Standard care","n":280,"value":11.3}],"hr":0.62,"ci":[0.52,0.74],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"},{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care","value":8.7},{"name":"Standard care","value":3.4}],"hr":0.4,"ci":[0.29,0.57],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"}],"replication":"Consistent with TheraP (phase 2, 177Lu-PSMA-617 vs cabazitaxel: higher PSA response, similar OS) and with PSMAfore in an earlier line.","route":"/trials/vision/"}
{"id":"beta-then-alpha","kind":"pairing","name":"Beta radioligand → alpha radioligand","aka":[],"tldr":"After lutetium therapy stops working, an actinium version of the same drug can still produce responses.","summary":"This sequence pairing follows Radioligand therapy (beta emitters) with Targeted alpha therapy using the same targeting molecule: after lutetium stops working, an actinium version of the same drug can still produce responses. Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic or small-volume disease cannot repair, as explained in the Alpha vs beta emitters entry. In Prostate cancer, Actinium-225 PSMA agents after Lutetium-177 vipivotide tetraxetan produced PSA responses in retrospective series, and phase 3 trials (AcTION, AlphaBreak) are ongoing. In Neuroendocrine tumours, Actinium-225 DOTATATE (RYZ101) is being tested in ACTION-1 after Lutetium-177 dotatate, so the evidence is retrospective and phase 1/2 with phase 3 pending.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT06402331: AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","url":"https://clinicaltrials.gov/study/NCT06402331"}],"tags":[],"related":["lu-177","ac-225"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto","ac225-psma","lutathera","ryz101"],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"radioligand-therapy","b":"targeted-alpha-therapy","rationale":"Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic, or small-volume disease cannot repair.","evidence":"Retrospective and phase 1/2; phase 3 pending.","pairingType":"sequence","route":"/pairings/beta-then-alpha/"}
{"id":"prrt-then-alpha-net","kind":"pairing","name":"Beta PRRT → alpha PRRT","aka":[],"tldr":"When lutetium radioligand therapy stops working, alpha-emitting versions can still control the disease.","summary":"This sequence moves from beta-emitting lutetium-177 dotatate to an alpha-emitting radioligand, 212Pb-DOTAMTATE, when beta PRRT stops controlling a neuroendocrine tumour. Alpha particles deliver oxygen-independent clustered DNA damage that beta-resistant clones cannot repair, so the same somatostatin receptor target can be attacked again with a more destructive payload. The phase 2 ALPHAMEDIX-02 trial included a PRRT-exposed cohort in which disease control was maintained in most patients, and ACTION-1 is the randomised phase 3 test of 225Ac-DOTATATE after 177Lu. The pairing belongs to the wider topic of alpha versus beta emitters and targeted alpha therapy.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05153772: ALPHAMEDIX-02","url":"https://clinicaltrials.gov/study/NCT05153772"},{"label":"ClinicalTrials.gov NCT05477576: ACTION-1","url":"https://clinicaltrials.gov/study/NCT05477576"}],"tags":[],"related":["lu-177","ac-225","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":["alphamedix-02","action-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"lutathera","b":"alphamedix","rationale":"Alpha particles deliver oxygen-independent clustered DNA damage that beta-resistant clones cannot repair.","evidence":"Phase 2 (AlphaMedix); phase 3 pending (ACTION-1).","pairingType":"sequence","route":"/pairings/prrt-then-alpha-net/"}
{"id":"psma-pet-to-rlt","kind":"pairing","name":"PSMA PET → PSMA radioligand therapy","aka":[],"tldr":"The scan shows whether the target is there; the treatment uses the same address. Only patients whose tumours light up are treated.","summary":"This diagnostic-therapeutic pairing links PSMA PET to Radioligand therapy (beta emitters) against PSMA in Prostate cancer: the scan shows whether the target is there, the treatment uses the same address, and only patients whose tumours light up are treated. Identical ligand chemistry means imaging biodistribution predicts therapeutic biodistribution and enables dosimetry. VISION and PSMAfore required PSMA PET positivity, so the pairing is embedded in phase 3 design and drug labels, and the standardised uptake value predicts response. The linked agents are Piflufolastat F-18 / Pylarify TruVu and Lutetium-177 vipivotide tetraxetan, and the pairing is the archetype of Theranostics now being copied for FAP, TROP2, HER2 and CAIX.","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03392428: TheraP (ANZUP 1603)","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":[],"related":["f-18","lu-177"],"indications":["prostate"],"sections":[],"technologies":[],"targets":["psma"],"drugs":["pylarify","pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"psma-pet","b":"radioligand-therapy","rationale":"Identical ligand chemistry means imaging biodistribution predicts therapeutic biodistribution; also enables dosimetry.","evidence":"Embedded in phase 3 design and labels.","pairingType":"diagnostic-therapeutic","route":"/pairings/psma-pet-to-rlt/"}
{"id":"sstr-pet-to-prrt","kind":"pairing","name":"SSTR PET → PRRT","aka":[],"tldr":"SSTR PET followed by PRRT is the original theranostic pair: the scan with the diagnostic isotope decides who gets the same molecule with the therapeutic isotope.","summary":"This diagnostic-therapeutic pairing links somatostatin receptor PET, using gallium-68 or copper-64 DOTATATE, to peptide receptor radionuclide therapy with lutetium-177 dotatate or 177Lu-edotreotide in neuroendocrine tumours. Because the imaging and therapeutic agents share identical peptide chemistry, the biodistribution seen on the scan predicts where the therapy will be delivered, which is the founding logic of theranostics. Every pivotal PRRT trial, including NETTER-1, NETTER-2 and COMPETE, required SSTR-avid disease on imaging, and both the intensity of uptake, graded on the Krenning scale, and the absence of FDG-avid lesions lacking SSTR predict benefit. The same template was later copied by PSMA theranostics in prostate cancer.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03049189: COMPETE","url":"https://clinicaltrials.gov/study/NCT03049189"}],"tags":[],"related":["ga-68","cu-64","lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":[],"targets":["sstr2"],"drugs":["lutathera","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"sstr-pet","b":"prrt","rationale":"Identical peptide chemistry means imaging biodistribution predicts therapy delivery.","evidence":"Embedded in all pivotal PRRT trials.","pairingType":"diagnostic-therapeutic","route":"/pairings/sstr-pet-to-prrt/"}
{"id":"molecular-imaging-roadmap","kind":"roadmap","name":"Molecular imaging roadmap: FDG → PSMA → FAP → antigen and immune PET","aka":[],"tldr":"From a sugar tracer that lights up most cancers to tracers that show a single protein, a stromal cell type, or the immune cells inside a tumour.","summary":"The molecular imaging roadmap moves from PET scanners and FDG, made routine by PET/CT, to receptor tracers such as 68Ga-DOTATATE and PSMA PET that outperform anatomic imaging and enable theranostics. The current step adds stromal FAPI PET and total-body scanners, and the emerging step brings drug-target and immune PET: TROP2, HER2, B7-H3 and Nectin-4 tracers to select and sequence ADCs, CD8 and granzyme PET to monitor immunotherapy, and PARP PET. The speculative end is multi-tracer same-day imaging, PET-guided adaptive radiotherapy and imaging-derived digital twins. Each new tracer converts a biopsy biomarker into a whole-body map; the route sits in the Imaging section and links PET, PET/CT, FDG PET, PSMA PET, FAPI PET, TROP2 PET, HER2 PET, immuno-PET, PARP PET and PET/MRI.","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms (Science 2020)","url":"https://doi.org/10.1126/science.abb9601"}],"tags":[],"related":["ga-68"],"indications":[],"sections":[],"technologies":["pet","pet-ct","fdg-pet","psma-pet","fapi-pet","trop2-pet","her2-pet","immuno-pet","parp-pet","pet-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1975-2001","title":"PET and FDG","description":"PET scanners (1975) and FDG (1976) developed; FDG PET adopted for lymphoma, lung, melanoma staging in the 1990s; PET/CT (2001) makes it routine.","refs":["fdg-pet","pet-ct"],"status":"historic"},{"era":"2008-2020","title":"Receptor PET: SSTR and PSMA","description":"68Ga-DOTATATE (Netspot 2016) and 68Ga/18F-PSMA (2020-21) show receptor tracers outperform anatomic imaging and enable theranostics.","refs":["psma-pet","sstr2"],"status":"historic"},{"era":"2018-2026","title":"Stromal PET and total-body scanners","description":"FAPI tracers image >90% of epithelial cancers with high contrast; registrational trials underway. Total-body PET (uEXPLORER, Quadra) enables 40x sensitivity, low-dose paediatric and dynamic imaging. 18F-FES (ER) approved 2020; 89Zr-girentuximab (CAIX) filed. Pylarify TruVu approved 2026.","refs":["fapi-pet","pet-ct","united-imaging","pylarify"],"status":"current"},{"era":"2024-2028","title":"Drug-target and immune PET","description":"TROP2, HER2, B7-H3, Nectin-4 antibody and nanobody tracers to select and sequence ADCs; CD8 and granzyme PET to predict and monitor immunotherapy response; PARP PET for PARP-inhibitor selection; AI quantification and radiomics on standard scans.","refs":["trop2-pet","her2-pet","immuno-pet","parp-pet"],"status":"emerging"},{"era":"2028+","title":"Speculative","description":"Multi-tracer same-day imaging on total-body PET; PET-guided adaptive radiotherapy (biology-guided RT); routine antigen PET before every ADC; imaging-derived digital twins of tumour heterogeneity feeding treatment algorithms.","refs":[],"status":"speculative"}],"watch":[],"route":"/roadmaps/molecular-imaging-roadmap/"}
{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","aka":[],"tldr":"The radiopharmaceutical roadmap runs eighty years from radioactive iodine for thyroid cancer to alpha-emitting drugs for prostate and neuroendocrine cancers, with isotope supply as the limiting factor.","summary":"The radiopharmaceutical roadmap runs from radioiodine curing differentiated thyroid cancer, the first theranostic, through radium-223 and Lutathera with its matched 68Ga-DOTATATE PET, to PSMA PET and Pluvicto building the first radioligand franchise. The current steps move Pluvicto and Lutathera into earlier lines amid an M&A wave, while the emerging step brings 225Ac and 212Pb alpha emitters and new targets such as FAP, GRPR, CAIX and B7-H3 into trials, with isotope supply as the limiting factor. The speculative end imagines radioligands as a standard modality with pan-cancer FAP theranostics and personalised dosimetry. The route links radioligand therapy, targeted alpha therapy, PSMA PET and FAPI PET, prostate, thyroid and neuroendocrine cancers, and the manufacturing bottleneck.","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"}],"tags":[],"related":["ga-68","ac-225","ra-223","pb-212"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy","psma-pet","fapi-pet","radioimmunotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1946-2000","title":"Radioiodine and early radioimmunotherapy","description":"131I cures differentiated thyroid cancer, the first theranostic. Strontium-89 and samarium-153 palliate bone pain. 90Y-ibritumomab and 131I-tositumomab (2002-03) work in lymphoma but fail commercially.","refs":["thyroid"],"status":"historic"},{"era":"2013-2018","title":"Radium-223 and Lutathera","description":"Radium-223 (ALSYMPCA, 2013) is the first alpha emitter approved, for bone metastases. 177Lu-DOTATATE (NETTER-1, 2018) establishes the modern peptide receptor radionuclide therapy paradigm with a matched 68Ga-DOTATATE PET.","refs":["lutathera","sstr2"],"status":"historic"},{"era":"2020-2022","title":"PSMA theranostics","description":"PSMA PET approved (68Ga-PSMA-11 2020, Pylarify 2021); Pluvicto approved (VISION, 2022). Novartis builds the first radioligand commercial franchise; supply and site-capacity constraints appear.","refs":["psma-pet","pluvicto","vision","pylarify"],"status":"current"},{"era":"2023-2026","title":"Earlier lines, consolidation, and an M&A wave","description":"PSMAfore moves Pluvicto pre-chemotherapy (2025), NETTER-2 moves Lutathera to first line (2024); 2026 label expansions. BMS buys RayzeBio ($4.1B), AstraZeneca buys Fusion ($2.4B), Lilly buys Point; Bayer, Sanofi, Novartis expand. Pylarify TruVu approved March 2026. ITM-11 reads out a positive phase 3.","refs":["psmafore","ryz101","fusion-pharma","rayzebio","itm"],"status":"current"},{"era":"2026-2029","title":"Alpha emitters and new targets","description":"225Ac-PSMA (Novartis, Bayer Trillium, Fusion FPI-2265), 225Ac-DOTATATE (RYZ101) and 212Pb-DOTAMTATE are in phase 3; FAP radioligands (FAP-2286) are in phase 2; GRPR, CAIX, B7-H3, DLL3 radioconjugates are in early trials. TerraPower's Philadelphia Ac-225 plant aims for a 20-fold supply increase. Dosimetry-guided dosing enters trials.","refs":["ac225-psma","ryz101","fap-2286","terrapower-isotopes","orano-med","dosimetry"],"status":"emerging"},{"era":"2029+","title":"Speculative: radioligands as a standard modality","description":"Alpha therapy in hormone-sensitive prostate cancer and after ADC failure; pan-cancer FAP theranostics; radio-ADCs and pretargeting; combination with PARP inhibitors, IO, and ADCs; automated decentralised radiopharmacies; total-body PET for ultra-low-dose dosimetry.","refs":["radioimmunotherapy","beta-then-alpha","pet-ct"],"status":"speculative"}],"watch":[],"route":"/roadmaps/radiopharma-roadmap/"}
{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","aka":[],"tldr":"When ADCs against a surface protein stop working because the payload no longer kills, use the same protein to deliver radiation instead.","summary":"When ADCs against a surface protein stop working because the payload no longer kills, this idea uses the same protein to deliver radiation instead. Antigen often persists after ADC failure with resistance at the payload level, so a 225Ac- or 177Lu-labelled anti-TROP2 or anti-HER2 antibody would bypass efflux, TOP1 mutations and SLFN11 loss, and crossfire would cover antigen-heterogeneous neighbours. The test is a phase 1 of a HER2 or TROP2 radioimmunoconjugate in ADC-refractory breast cancer, with antigen PET selection and dosimetry. Speculative in maturity, it complements Payload-class switching as the rule for ADC sequencing and draws on radio-antibody and radio-ADC, targeted alpha therapy and TROP2 PET.","asOf":"2026-09-04","links":[],"tags":[],"related":["lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioimmunotherapy","targeted-alpha-therapy","trop2-pet"],"targets":["trop2","her2","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"225Ac- or 177Lu-labelled anti-TROP2 or anti-HER2 antibodies produce responses in patients progressing on TROP2 or HER2 ADCs with retained antigen expression on PET.","rationale":"Radiation cytotoxicity is independent of drug efflux and payload-specific resistance; crossfire covers antigen-heterogeneous neighbours.","test":"Run a phase 1 of a HER2 or TROP2 radioimmunoconjugate in ADC-refractory breast cancer with antigen PET selection and dosimetry.","maturity":"speculative","route":"/ideas/idea-alpha-after-adc/"}
{"id":"idea-alpha-first-mhspc","kind":"idea","name":"Alpha-emitting PSMA therapy at first metastatic diagnosis","aka":[],"tldr":"If Pluvicto helps at first diagnosis, an alpha version might do more against microscopic disease, when tumour burden is smallest.","summary":"This speculative idea would give alpha-emitting PSMA therapy with actinium-225 at the first metastatic diagnosis of hormone-sensitive prostate cancer, alongside hormone therapy. Short-range alpha emission suits small-volume disease and is oxygen-independent, and early treatment avoids the PSMA heterogeneity of castration resistance; PSMAddition established beta-emitter therapy here. The hypothesis is deeper PSA nadirs and longer radiographic progression-free survival than lutetium-177 PSMA-617 at equal or lower salivary dose; salivary toxicity and actinium-225 supply are limiting. The test is a randomised phase 2 with PSMA PET-based dosimetry, salivary gland protection and the undetectable-PSA rate at one year as primary endpoint.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04720157: PSMAddition","url":"https://clinicaltrials.gov/study/NCT04720157"}],"tags":[],"related":["lu-177","ac-225"],"indications":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":["ac225-psma","pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":["psmaddition"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"225Ac-PSMA added to ADT + ARPI in high-volume de novo mHSPC produces deeper PSA nadirs and longer rPFS than 177Lu-PSMA-617 at equal or lower cumulative salivary dose.","rationale":"Short-range alpha emission suits small-volume disease; early treatment avoids PSMA heterogeneity that develops under castration resistance.","test":"Phase 2 randomised 225Ac-PSMA vs 177Lu-PSMA-617 in mHSPC with PSMA PET-based dosimetry, salivary gland protection, and undetectable-PSA rate at 12 months as primary.","maturity":"speculative","route":"/ideas/idea-alpha-first-mhspc/"}
{"id":"idea-caix-theranostics","kind":"idea","name":"CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy","aka":[],"tldr":"Almost every clear-cell kidney cancer carries the CAIX protein. Image it with one radioactive antibody, then treat with the same antibody carrying a therapeutic isotope.","summary":"Nearly every clear-cell renal cell carcinoma expresses carbonic anhydrase IX as a direct consequence of VHL loss, so the antigen is near-universal and stable. This theranostic idea images it with 89Zr-girentuximab PET, validated for diagnosis in ZIRCON, and then treats with the same antibody carrying 177Lu for beta emission or 225Ac for targeted alpha therapy. The rationale combines a stable target, the PSMA precedent in prostate cancer, and radiation-induced immunogenic cell death in a cancer that already responds to immunotherapy. STARLITE-1 and STARLITE-2 are testing 177Lu-girentuximab with nivolumab or cabozantinib, and the proposed test is a randomised phase 2 of 177Lu-girentuximab plus nivolumab versus nivolumab alone; Telix Pharmaceuticals is the linked company.","asOf":"2026-09-07","links":[{"label":"Shuch et al., ZIRCON: 89Zr-girentuximab PET-CT imaging of clear-cell renal cell carcinoma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(24)00402-9"}],"tags":[],"related":["zr-89","lu-177","ac-225"],"indications":["rcc"],"sections":[],"technologies":["caix-pet","radioligand-therapy","targeted-alpha-therapy","radioimmunotherapy"],"targets":[],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"177Lu- or 225Ac-girentuximab produces objective responses in ≥25% of heavily pretreated clear-cell RCC patients selected by CAIX PET, and synergises with PD-1 blockade.","rationale":"Stable antigen, theranostic pairing proven in prostate cancer (PSMA), and radiation-induced immunogenic cell death in an immunotherapy-responsive tumour.","test":"Randomised phase 2 of 177Lu-girentuximab + nivolumab vs nivolumab after IO-TKI progression, PET-selected.","maturity":"early-clinical","route":"/ideas/idea-caix-theranostics/"}
{"id":"idea-cd8-pet-io","kind":"idea","name":"CD8 PET to stop or switch immunotherapy early","aka":[],"tldr":"Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.","summary":"Scan for T cells inside the tumour a few weeks after starting immunotherapy, and change course if they have not arrived. Tracers such as 89Zr-crefmirlimab, a CD8 minibody, and 18F-AraG image T-cell infiltration and activation, and an early increase has tracked response in phase 2 studies. Response to checkpoint blockade requires T-cell infiltration, CT changes lag by months and pseudoprogression confounds RECIST, so an absent CD8 PET signal at week 4 could identify non-responders early. The test is a prospective trial in NSCLC or melanoma with week-4 CD8 PET, randomising PET non-responders to continue or switch. At early-clinical maturity it addresses the bottleneck No one can predict who responds to immunotherapy.","asOf":"2026-09-04","links":[{"label":"Farwell et al., CD8-targeted PET imaging of tumour-infiltrating T cells in patients with cancer: a phase 1 first-in-human study of 89Zr-Df-IAB22M2C (Journal of Nuclear Medicine 2021)","url":"https://doi.org/10.2967/jnumed.121.262485"}],"tags":[],"related":["f-18","zr-89"],"indications":[],"sections":[],"technologies":["immuno-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Absence of CD8 PET increase at week 4 identifies non-responders with >85% specificity, enabling early switch to alternative therapy.","rationale":"Response to checkpoint blockade requires T-cell infiltration; CT changes lag by months; pseudoprogression confounds RECIST.","test":"Run a prospective trial in NSCLC or melanoma with week-4 CD8 PET; randomise PET-non-responders to continue vs switch.","maturity":"early-clinical","route":"/ideas/idea-cd8-pet-io/"}
{"id":"idea-fap-theranostics-pancancer","kind":"idea","name":"FAP theranostics as a pan-cancer stromal strategy","aka":[],"tldr":"Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.","summary":"Rather than finding a different target for each cancer, this idea hits the cancer-associated fibroblasts that almost all solid tumours share. FAP-targeted alpha or beta radioligands such as FAP-2286 would be given to FAPI-PET-avid pancreatic, gastric and sarcoma patients irrespective of tumour-cell genotype, delivering radiation to the stroma with crossfire into adjacent tumour cells and depleting the fibroblasts that exclude T cells. Stroma is genetically stable, so resistance mutations are not expected. The test is phase 2 FAP-2286 cohorts selected by FAPI PET, with paired biopsies and a PD-1 combination in pancreatic cancer. At early-clinical maturity it addresses the bottleneck Cold tumours and the immunosuppressive microenvironment.","asOf":"2026-09-04","links":[{"label":"Kratochwil et al., 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer (Journal of Nuclear Medicine 2019)","url":"https://doi.org/10.2967/jnumed.119.227967"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["fapi-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":["fap"],"drugs":["fap-2286"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"FAP-targeted alpha or beta radioligands produce disease control in FAPI-PET-avid pancreatic, gastric, and sarcoma patients irrespective of tumour-cell genotype, and sensitise to immunotherapy by depleting immunosuppressive fibroblasts.","rationale":"Stroma is genetically stable (no resistance mutations); crossfire range of 177Lu (2 mm) covers adjacent tumour cells; CAF depletion relieves T-cell exclusion.","test":"Phase 2 FAP-2286 cohorts with FAPI PET selection and paired biopsies for CAF depletion and T-cell infiltration; combination with PD-1 in pancreatic cancer.","maturity":"early-clinical","route":"/ideas/idea-fap-theranostics-pancancer/"}
{"id":"idea-fund-academic-radiopharma-pipeline","kind":"idea","name":"A university cyclotron network with shared regulatory files for new tracers","aka":[],"tldr":"Most new cancer imaging agents and radioactive drugs start in university hospitals. A network sharing production, quality files and regulatory paperwork would get them into multi-centre trials years faster.","summary":"Academic radiopharmacy has repeatedly produced the agents the field now runs on (PSMA ligands and FAPI tracers from Heidelberg, DOTATATE from Basel and Rotterdam) but each centre re-creates production, quality control and regulatory documentation. A funded network of university cyclotrons and radiopharmacies would share drug master files, validated synthesis modules, GMP quality systems and a common clinical trial application template, so a tracer validated in one centre can be adopted in ten within months. It would also provide isotope purchasing at scale (gallium-68 generators, lutetium-177, actinium-225 allocation) for academic trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fap-theranostics-pancancer","radiopharma-roadmap","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["psma-pet","fapi-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["heidelberg-nct","peter-mac"],"pathways":[],"terms":[],"trials":[],"people":["uwe-haberkorn","frederik-giesel","hofman-michael"],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared network reduces the time from first-in-human of an academic tracer or radioligand to a five-centre trial from the current several years to under eighteen months, and doubles the number of academic radiopharmaceuticals entering multi-centre trials within four years.","rationale":"PSMA PET spread globally because academic centres shared precursors and methods informally; formalising that with shared regulatory files removes the largest delay. Germany's and the Netherlands' academic radiopharmacy networks demonstrate feasibility within a country.","test":"Fund a ten-centre network with a shared master file for two agents and measure time to multi-centre trial start and centres activated compared with agents developed without the network.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4,"route":"/ideas/idea-fund-academic-radiopharma-pipeline/"}
{"id":"idea-mced-plus-fapi","kind":"idea","name":"FAPI PET as the workup for MCED positives","aka":[],"tldr":"When a blood test says 'cancer signal, origin unclear', a FAPI PET scan may find it where FDG cannot.","summary":"When a blood test reports a cancer signal of unclear origin, this idea sends the patient for FAPI PET/CT rather than FDG PET as the first-line work-up. Many MCED-positive patients have no cancer found on standard imaging, which creates anxiety and cost, whereas FAPI PET is more sensitive than FDG in pancreatic, gastric, low-grade and peritoneal disease, exactly the cancers MCED promises to catch, and has low background in liver, brain and bowel. The test is a prospective diagnostic study nested in a Galleri deployment such as the NHS or a PATHFINDER-like cohort, randomising FDG versus FAPI PET. Speculative in maturity, it addresses the bottleneck The hardest cancers are found late and is linked from the ideas on a 28-day MCED-positive resolution pathway and whole-population interception.","asOf":"2026-09-04","links":[{"label":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms (The Lancet 2023)","url":"https://doi.org/10.1016/S0140-6736(23)01700-2"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["fapi-pet","fdg-pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"FAPI PET/CT increases the cancer detection rate and reduces time to diagnosis in MCED-positive, FDG-negative or tissue-of-origin-uncertain patients.","rationale":"Complementary biology (stroma vs glucose); FAPI has low background in liver, brain, and bowel.","test":"Prospective diagnostic study nested in a Galleri deployment (e.g., NHS or PATHFINDER-like) randomising FDG vs FAPI PET as first-line workup.","maturity":"speculative","route":"/ideas/idea-mced-plus-fapi/"}
{"id":"idea-mfbg-pet-replaces-mibg","kind":"idea","name":"18F-MFBG PET replacing 123I-MIBG scintigraphy","aka":[],"tldr":"A same-day PET tracer could replace the two-day, low-resolution MIBG scan children now undergo repeatedly.","summary":"Children with neuroblastoma repeatedly undergo 123I-MIBG scintigraphy, a two-day, low-resolution scan, and this idea proposes replacing it with same-day 18F-MFBG PET. 18F-meta-fluorobenzylguanidine uses the same norepinephrine-transporter biology as MIBG but gains PET resolution and 18F logistics, needs no sedation across two days, and early data show higher lesion detection. The hypothesis is that MFBG PET/CT detects more lesions than MIBG SPECT with equal specificity, and that Curie-type scoring on MFBG predicts outcome at least as well. Prospective paired comparisons are under way at MSK and in COG imaging studies and an NDA is in progress; at an early clinical stage, it sits within the paediatric oncology roadmap alongside the MIBG theranostics and PET records.","asOf":"2026-09-07","links":[{"label":"Pandit-Taskar et al., Biodistribution and dosimetry of 18F-meta-fluorobenzylguanidine: a first-in-human PET study (Journal of Nuclear Medicine 2017)","url":"https://doi.org/10.2967/jnumed.117.193169"}],"tags":[],"related":["f-18","i-123"],"indications":["neuroblastoma"],"sections":[],"technologies":["mibg-theranostics","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"18F-MFBG PET/CT detects more lesions than 123I-MIBG SPECT with equal specificity, and Curie-type scoring on MFBG predicts outcome at least as well.","rationale":"MFBG uses the same norepinephrine-transporter biology as MIBG but with PET resolution and 18F logistics.","test":"Paired prospective comparison in newly diagnosed and relapsed patients; response prediction analysis.","maturity":"early-clinical","route":"/ideas/idea-mfbg-pet-replaces-mibg/"}
{"id":"idea-net-antagonist-ligands","kind":"idea","name":"SSTR antagonist radioligands to increase tumour dose","aka":[],"tldr":"Radioligand therapy for neuroendocrine tumours built on somatostatin receptor antagonists rather than the agonists used today: antagonists bind the receptor in every state and are not internalised, so they occupy several times more sites per cell and deliver more radiation per dose. The test is a randomised phase 2 against agonist lutetium therapy.","summary":"The idea is to build peptide receptor radionuclide therapy for neuroendocrine tumours on somatostatin receptor 2 antagonists rather than the agonists used today. Antagonists bind receptors in every conformational state and are not internalised, so they occupy several times more binding sites on each cell and deliver more radiation per dose. First-in-human studies of the antagonist 177Lu-satoreotide tetraxetan showed higher tumour uptake and dose than agonists, and early trials report responses in patients refractory to agonist PRRT. The hypothesis is higher response rates at an equivalent renal dose, including in tumours with low SSTR2 expression; the test is a randomised phase 2 of antagonist versus agonist 177Lu-PRRT in grade 1 to 2 gastroenteropancreatic NETs.","asOf":"2026-09-07","links":[{"label":"Reidy-Lagunes et al., Phase 1 trial of the SSTR antagonist radioligand 177Lu-satoreotide tetraxetan in neuroendocrine tumours (Clinical Cancer Research 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-19-1026"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["prrt"],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Antagonist PRRT achieves higher response rates than agonist PRRT at equivalent renal dose, including in low-SSTR-expressing tumours.","rationale":"Antagonists bind receptors in all conformational states and are not internalised, increasing binding sites several-fold.","test":"Randomised phase 2 antagonist vs agonist 177Lu-PRRT in grade 1-2 GEP-NETs.","maturity":"early-clinical","route":"/ideas/idea-net-antagonist-ligands/"}
{"id":"idea-net-dosimetry-prrt","kind":"idea","name":"Dosimetry-personalised PRRT instead of four fixed cycles","aka":[],"tldr":"Measure the radiation each patient's tumour and kidneys actually absorb and adjust the number and size of doses, instead of giving everyone four identical cycles.","summary":"The idea is to personalise peptide receptor radionuclide therapy with lutetium-177 dotatate or 177Lu-edotreotide by measuring the radiation each patient's tumour, kidneys and marrow actually absorb on SPECT/CT after each cycle, and adjusting the number and size of doses. The standard of 7.4 GBq for four cycles leaves many patients under-dosed relative to renal and marrow limits, uptake varies widely, and retrospective dosimetry shows tumour absorbed dose correlates with response. The hypothesis is that dosimetry-guided PRRT raises cumulative tumour dose and response rate without exceeding organ limits. The test is a randomised phase 2 of individualised versus fixed activity; P-PRRT in Canada is already testing this, and the idea addresses the wrong-doses bottleneck.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03049189: COMPETE","url":"https://clinicaltrials.gov/study/NCT03049189"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["prrt","spect"],"targets":[],"drugs":["lutathera","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dosimetry-guided PRRT increases cumulative tumour dose and response rate without exceeding renal/marrow limits, versus fixed dosing.","rationale":"Wide inter-patient variation in uptake; SPECT/CT after each cycle makes dosimetry feasible.","test":"Randomised phase 2 of individualised vs fixed activity with ORR and PFS endpoints.","maturity":"early-clinical","route":"/ideas/idea-net-dosimetry-prrt/"}
{"id":"idea-psma-pet-guided-mdt","kind":"idea","name":"PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer","aka":[],"tldr":"When PSMA PET finds only a few spots after surgery, zap each spot with focused radiation and delay or avoid lifelong hormone therapy.","summary":"The idea is to use PSMA PET after prostate surgery to find the few sites of recurrence and treat each with stereotactic radiotherapy plus short-course androgen deprivation. The oligometastatic state is real in prostate cancer, the radiotherapy is ablative and cheap, and PSMA PET removes the staging blind spot that undermined older trials such as ORIOLE and STOMP. The hypothesis is better metastasis-free and ADT-free survival than systemic therapy alone, though whether it changes survival or merely postpones hormone therapy is unproven. The test is a randomised phase 3 with PSMA PET at baseline and progression and ctDNA as a stratifier; PEACE V/STORM and NRG GU011 are under way, so it is being tested at scale.","asOf":"2026-09-06","links":[{"label":"ORIOLE: observation versus stereotactic ablative radiation for oligometastatic prostate cancer (JAMA Oncology 2020)","url":"https://doi.org/10.1001/jamaoncol.2020.0147"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PSMA-PET-directed SBRT to ≤5 metastases, with short-course ADT, improves metastasis-free and ADT-free survival versus systemic therapy alone in oligorecurrent disease.","rationale":"Oligometastatic state is real in prostate cancer; SBRT is ablative and cheap; PSMA PET removes the staging blind spot that undermined older trials.","test":"Randomised phase 3 with PSMA PET at baseline and progression, ADT-free survival and MFS endpoints, ctDNA and PSMA-PET total-volume as stratifiers.","maturity":"being-tested-at-scale","route":"/ideas/idea-psma-pet-guided-mdt/"}
{"id":"idea-reg-ac225-accelerator-pharmacopoeia","kind":"idea","name":"Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit","aka":[],"tldr":"Actinium-225 can be made in particle accelerators, but the product contains a trace of a long-lived impurity that regulators have not agreed how to handle. Settle the limit and build the hubs.","summary":"Proton irradiation of radium-226 yields actinium-225 with a small admixture of actinium-227 (half-life 21.8 years), while electron linac photonuclear and high-energy spallation routes differ in impurity profile. Without a harmonised monograph, each producer negotiates specifications with each regulator, slowing investment. The proposal is a joint European, US and Japanese pharmacopoeia monograph setting actinium-227 and other radionuclidic impurity limits based on dosimetry and waste handling, paired with public co-investment in three to five regional cyclotron or linac hubs sized for clinical supply.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A harmonised monograph published within two years is followed by at least three accelerator producers reaching GMP supply, and clinical trial sponsors report isotope supply as the limiting factor in fewer than 10% of alpha therapy trials, down from the majority today.","rationale":"Molybdenum-99 supply diversified only when regulators agreed specifications for non-HEU and accelerator-produced material. Investment follows regulatory certainty.","test":"Commission the dosimetric analysis of actinium-227 contamination at candidate limits, convene the pharmacopoeial groups, and track producer investment decisions and trial supply reports before and after publication.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3,"route":"/ideas/idea-reg-ac225-accelerator-pharmacopoeia/"}
{"id":"idea-reg-alpha-emitter-portfolio","kind":"idea","name":"Fund alpha emitters beyond actinium-225: lead-212, terbium-149 and astatine-211","aka":[],"tldr":"Almost every alpha cancer therapy in development relies on one scarce isotope. Developing several alternatives at once would stop the whole field waiting on a single supply chain.","summary":"Actinium-225 dominates targeted alpha therapy pipelines, but lead-212 (from thorium-228/radium-224 generators, used by Orano Med and Perspective Therapeutics), astatine-211 (cyclotron-produced, short half-life, suited to regional supply) and terbium-149 have complementary properties and independent supply routes. The proposal is a public-private programme that funds isotope-agnostic chelator and linker chemistry, comparative dosimetry and small head-to-head clinical studies so that a given targeting ligand can be paired with whichever alpha emitter is available, and that de-risks generator and cyclotron capacity for each.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["ac-225","pb-212","at-211","ra-224"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":["orano-med","perspective-therapeutics"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years at least two alpha emitters other than actinium-225 reach late-stage trials with GMP supply exceeding clinical demand, and the proportion of alpha therapy trials delayed by isotope supply falls below 10%.","rationale":"Diversifying supply has repeatedly been cheaper than expanding a single constrained route; lead-212 generators are already in clinical use and astatine-211 chemistry has matured at several centres.","test":"Award funding to three ligand programmes to produce matched actinium-225, lead-212 and astatine-211 versions and compare biodistribution, dosimetry and manufacturability in first-in-human studies.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":5,"route":"/ideas/idea-reg-alpha-emitter-portfolio/"}
{"id":"idea-reg-isotope-supply-observatory","kind":"idea","name":"A global medical isotope supply observatory with forecasts and shortage alerts","aka":[],"tldr":"Nobody publishes how much cancer isotope is made, where, or when supply will fall short. A public observatory would let hospitals and investors plan.","summary":"Supply and demand for lutetium-177, actinium-225, iodine-131 and their precursors are opaque; producers guard volumes, and shortages surface only when clinics cancel doses. The proposal is an observatory, hosted by the IAEA or OECD NEA with WHO, that collects confidential production and capacity data from producers under aggregation rules, publishes quarterly supply-demand balances and five-year forecasts, and issues shortage alerts to clinics and regulators. It would also track trial-stage demand so producers can invest ahead of approvals.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["lu-177","ac-225","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publication of forecasts is followed by earlier capacity investment decisions (measured by announced projects relative to forecast shortfalls) and a fall in unanticipated clinic-level shortages within three years.","rationale":"Transparent supply data (as in energy and food markets) reduce boom-bust investment and allow health systems to plan; the molybdenum-99 experience showed that opaque supply led to repeated crises.","test":"Establish the observatory for lutetium-177 first, publish two years of quarterly balances, and evaluate accuracy of forecasts and changes in shortage reports.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2,"route":"/ideas/idea-reg-isotope-supply-observatory/"}
{"id":"idea-reg-legacy-radium-recovery-ac225","kind":"idea","name":"Recover legacy radium-226 sources worldwide as the feedstock for actinium-225","aka":[],"tldr":"Thousands of old radium sources sit in hospital and industrial storage. They are exactly the raw material needed to make actinium-225, the scarcest cancer isotope.","summary":"Actinium-225 supply from thorium-229 generators (the legacy US and Russian stockpiles) is limited to tens of curies a year, far short of projected demand for alpha radioligand therapy. Accelerator routes (radium-226 irradiated in cyclotrons, linacs or via spallation at TRIUMF) scale with radium feedstock. Radium-226 exists in large quantities in disused brachytherapy sources, industrial gauges and uranium mill tailings, currently classed as waste and expensive to store. The proposal is a coordinated recovery, purification and target-fabrication programme run with the IAEA and national nuclear agencies, offering source holders free disposal in exchange for the material.","asOf":"2026-09-08","links":[{"label":"IAEA on actinium-225 supply","url":"https://www.iaea.org/newscenter/news/actinium-225-production-and-supply"}],"tags":[],"related":["ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":["ac225-psma","ryz101"],"companies":["terrapower-isotopes","orano-med"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Recovered radium-226 sufficient to supply multiple accelerator producers can be secured within five years at a cost per curie of actinium-225 below the thorium-generator route, lifting global actinium-225 output by an order of magnitude.","rationale":"Radium disposal is already a cost that source holders would pay to avoid, and purification chemistry is established. The binding constraint on the accelerator route is licensed feedstock, not physics.","test":"Inventory recoverable radium-226 in ten countries, run a pilot recovery of 50 grams with one accelerator producer, and price the resulting actinium-225 against current generator supply.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":4,"route":"/ideas/idea-reg-legacy-radium-recovery-ac225/"}
{"id":"idea-reg-medical-isotope-reactor-reserve","kind":"idea","name":"A coordinated reserve and shared schedule for the world's medical isotope reactors","aka":[],"tldr":"A handful of ageing research reactors make most cancer isotopes. Coordinating their maintenance and funding reserve capacity would prevent the shortages that stop treatments.","summary":"Lutetium-177, iodine-131 and molybdenum-99 depend on a few research reactors (HFR Petten, BR2, MARIA, SAFARI-1, OPAL, several in Russia and the US), most over 50 years old. The OECD Nuclear Energy Agency's High-Level Group on Medical Radioisotopes coordinated molybdenum-99 after the 2009-10 crisis. The proposal is to extend that model formally to therapeutic isotopes: shared outage scheduling, an agreed reserve capacity margin funded by a per-dose levy, and public co-financing of the next generation of producers (PALLAS in the Netherlands, accelerator-based SHINE, new irradiation positions in existing reactors).","asOf":"2026-09-08","links":[{"label":"OECD NEA medical radioisotopes","url":"https://www.oecd-nea.org/jcms/pl_26262/medical-radioisotopes"}],"tags":[],"related":["mo-99","lu-177","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Coordinated scheduling and reserve capacity reduce clinic-reported therapeutic isotope shortage weeks by at least 80% and keep lutetium-177 spot prices stable during planned reactor outages.","rationale":"The molybdenum-99 experience showed that coordination, not new physics, ended a supply crisis; therapeutic isotopes now face the same concentration of supply with faster-growing demand.","test":"Publish a shared outage calendar and reserve-margin target for lutetium-177 producers within a year; track clinic-reported dose cancellations and prices against the prior three years.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5,"route":"/ideas/idea-reg-medical-isotope-reactor-reserve/"}
{"id":"idea-reg-regional-radiopharmacy-hubs","kind":"idea","name":"Regional radiopharmacy hubs and harmonised transport rules for short-lived isotopes","aka":[],"tldr":"Radioactive cancer drugs decay while they travel and get stuck at borders. Regional production and simpler transport rules would get more doses to patients on time.","summary":"Radioligand therapies are often labelled centrally and shipped internationally, losing activity to decay and to customs delays; dangerous goods rules differ by country and carrier. The proposal is a network of regional GMP radiopharmacies (one per few million population) receiving bulk isotope and cold kits, labelling on demand, and delivering same-day, combined with an IAEA-brokered harmonisation of Class 7 transport paperwork and pre-clearance for medical isotopes at major airports.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional labelling and pre-clearance reduce the share of radioligand doses cancelled or postponed for supply reasons from roughly 5-10% to below 1% and reduce shipped activity per delivered dose by at least a quarter.","rationale":"Nuclear medicine already runs this way for diagnostic isotopes (technetium generators, fluorine-18 cyclotron networks). Therapeutic isotopes have longer half-lives but far higher per-dose value, so the economics of regional hubs are favourable.","test":"Pilot two regional hubs in a large country and measure dose cancellation rates, shipped activity per dose and cost per dose against central supply over one year.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3,"route":"/ideas/idea-reg-regional-radiopharmacy-hubs/"}
{"id":"idea-reg-yb176-enrichment-capacity","kind":"idea","name":"Build Western ytterbium-176 enrichment so lutetium-177 has more than one supplier","aka":[],"tldr":"The lutetium used in approved prostate and neuroendocrine cancer treatments is made from an enriched metal that comes mostly from Russia. Making it elsewhere would secure supply.","summary":"No-carrier-added lutetium-177 is produced by irradiating enriched ytterbium-176, most of which has historically come from Russian electromagnetic separators. Demand is rising steeply with Pluvicto, Lutathera and pipeline radioligands. Several companies (ASP Isotopes, ITM, SHINE and others) are developing laser or centrifuge enrichment in North America and Europe. The proposal is an advance market commitment by health systems and manufacturers to buy a guaranteed volume of Western-enriched ytterbium-176 at a floor price for ten years, with a strategic buffer stock, mirroring how vaccine advance commitments created capacity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":["itm","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Advance commitments bring at least two non-Russian enrichment facilities to commercial output within four years, supplying more than half of global ytterbium-176 demand, and lutetium-177 supply interruptions to clinics fall to zero.","rationale":"Enrichment is a capital-intensive, low-margin step whose investors need demand certainty; the clinical demand is now visible and growing, and geopolitical risk to a single-source supply chain is evident.","test":"Model demand to 2035 with the major radioligand producers, structure a joint offtake agreement, and measure delivered enrichment capacity and supply-interruption reports over five years.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":4,"route":"/ideas/idea-reg-yb176-enrichment-capacity/"}
{"id":"idea-total-body-pet-dosimetry","kind":"idea","name":"Total-body PET for personalised radioligand dosing","aka":[],"tldr":"Ultra-sensitive whole-body scanners can measure exactly where a radioactive drug goes at tiny tracer doses, allowing each patient's therapeutic dose to be tailored.","summary":"Radioligand therapy is given at fixed activity despite wide variation in tumour and kidney dose, so this idea uses ultra-sensitive total-body PET with 44Sc- or 89Zr-labelled analogues to measure each patient's pharmacokinetics before treatment and tailor the therapeutic dose. Dosimetry-guided prescription of 177Lu-PSMA is expected to raise tumour absorbed dose and response without exceeding kidney and marrow limits. Personalised dosimetry is established in radioiodine and SIRT, and total-body scanners from United Imaging and Siemens Healthineers remove the imaging-time and dose barriers. The test is a randomised trial of dosimetry-guided versus fixed-dose Pluvicto in prostate cancer with PSA50 and rPFS endpoints. At early-clinical maturity it addresses the bottleneck Wrong doses.","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"}],"tags":[],"related":["zr-89","sc-44","lu-177"],"indications":["prostate"],"sections":[],"technologies":["pet-ct","radioligand-therapy","spect"],"targets":[],"drugs":["pluvicto"],"companies":["united-imaging","siemens-healthineers"],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dosimetry-guided activity prescription for 177Lu-PSMA increases tumour absorbed dose and response without exceeding kidney and marrow limits, compared with fixed 7.4 GBq.","rationale":"Established in radioiodine and SIRT; total-body PET removes the imaging-time and dose barriers to pre-therapy dosimetry.","test":"Randomised dosimetry-guided vs fixed-dose Pluvicto trial with PSA50 and rPFS endpoints.","maturity":"early-clinical","route":"/ideas/idea-total-body-pet-dosimetry/"}
{"id":"idea-tr2-psma-volume-qualification","kind":"idea","name":"Qualify PSMA PET tumour volume as a validated imaging biomarker","aka":[],"tldr":"PSMA scans could measure prostate cancer burden and response far better than PSA, but no one has done the standardisation work to make the measurement trustworthy across scanners.","summary":"Total PSMA-positive tumour volume and SUV metrics predict outcome in metastatic prostate cancer and response to radioligand therapy, but acquisition, reconstruction and segmentation vary between centres. A QIBA-style profile (phantom calibration, harmonised reconstruction, validated segmentation software) followed by biomarker qualification for defined contexts of use (prognosis, response assessment) would let PSMA volume be used as an endpoint and selection tool in trials.","asOf":"2026-09-08","links":[{"label":"RSNA QIBA","url":"https://www.rsna.org/research/quantitative-imaging-biomarkers-alliance"}],"tags":[],"related":["psma-pet-to-rlt","idea-total-body-pet-dosimetry"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Harmonised PSMA volumetric measurements will achieve test-retest and inter-site coefficient of variation under 15% and will predict overall survival on radioligand therapy better than PSA response.","rationale":"FDG PET response criteria (PERCIST, Deauville) needed the same standardisation before adoption; PSMA PET is now widespread enough to justify it.","test":"A multi-centre phantom and test-retest study followed by retrospective validation on trial imaging from VISION and PSMAfore, then a qualification submission.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4,"route":"/ideas/idea-tr2-psma-volume-qualification/"}
{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","aka":[],"tldr":"Use a whole-body TROP2 scan instead of a single tissue stain to decide which patients get a TROP2 ADC, which one, and when to switch.","summary":"The proposal is to use a whole-body TROP2 PET scan, rather than a single tissue stain, to decide which patients receive a TROP2 ADC, which agent they get and when to switch. Baseline uptake and heterogeneity would predict benefit, and a fall in uptake at progression would signal antigen loss that should prompt a move to a non-TROP2 ADC rather than a second TROP2 agent. IHC on archival tissue failed to predict sacituzumab govitecan benefit, whereas PSMA PET already plays this role for Pluvicto and 89Zr-antibody and 68Ga-nanobody tracers image human tumours. The test is an imaging sub-study inside a first-line TNBC ADC trial, then a randomised PET-guided versus standard sequencing trial. At early-clinical maturity, it bears on the bottleneck Biomarkers are not validated or standardised.","asOf":"2026-09-04","links":[{"label":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"}],"tags":[],"related":["psma-pet-to-rlt","ga-68","zr-89"],"indications":[],"sections":[],"technologies":["trop2-pet","immuno-pet"],"targets":["trop2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Baseline TROP2 PET uptake (SUV, heterogeneity index) predicts PFS on TROP2 ADCs better than IHC, and a fall in uptake at progression indicates antigen-loss resistance that should prompt a switch to a non-TROP2 ADC rather than a second TROP2 agent.","rationale":"PSMA PET does exactly this for Pluvicto. TROP2 is internalising and abundant; 89Zr-antibody and 68Ga-nanobody tracers already image human tumours.","test":"Prospective imaging sub-study in a first-line TNBC ADC trial (e.g., a TROPION-Breast05 or sac-TMT cohort) correlating baseline and on-treatment TROP2 PET with response and PFS; then a randomised PET-guided vs standard sequencing trial.","maturity":"early-clinical","route":"/ideas/idea-trop2-pet-selection/"}
{"id":"clinicaltrials-gov","kind":"collection","name":"ClinicalTrials.gov","aka":[],"tldr":"ClinicalTrials.gov is the master list of clinical trials. Every trial on this site links to its record.","summary":"ClinicalTrials.gov is the registry and results database of more than 500,000 clinical studies worldwide, run by the NIH National Library of Medicine and released as public domain US Government work. Registration is mandatory for US trials, and API v2 gives structured access to eligibility criteria, arms, outcome measures and posted results, which makes it the backbone of any trial-matching tool. Every trial on Nuclide links to its ClinicalTrials.gov record, and the collection is tied to the technology AI trial matching and clinical decision support. It is also cited by bottleneck records including Trials enrol too few, too slowly, Failures are hidden, Data silos and Weak real-world evidence and registries, and by ideas such as One standing umbrella trial for all rare cancers in a country.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov","url":"https://clinicaltrials.gov"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://clinicaltrials.gov","holds":"Registry and results database of >500,000 clinical studies worldwide.","license":"Public domain (US Government)","maintainer":"NIH / NLM","route":"/collections/clinicaltrials-gov/"}
{"id":"prostate-cancer-foundation","kind":"collection","name":"Prostate Cancer Foundation (PCF)","aka":[],"tldr":"Michael Milken's prostate cancer foundation, which funded the science behind abiraterone, enzalutamide and PSMA therapy and runs a precision-oncology network in US veterans' hospitals.","summary":"Founded 1993 (as CaP CURE). PCF-funded research contributed to abiraterone, enzalutamide, radium-223, PSMA imaging and radioligands, and germline testing guidance; the PCF-VA network provides genomic testing and trials to veterans; the Young Investigator awards have trained a generation of researchers. Patient resources include the Prostate Cancer Patient Guide and a Black-community outreach programme; ZERO Prostate Cancer and Movember are major partner organisations for support and awareness.","asOf":"2026-09-08","links":[{"label":"PCF","url":"https://www.pcf.org/"},{"label":"ZERO Prostate Cancer","url":"https://zerocancer.org/"},{"label":"Movember","url":"https://us.movember.com/"}],"tags":["gap-fill","patient-org"],"related":["prostate","psma","psma-pet","pluvicto","abiraterone","enzalutamide","ra-223"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://www.pcf.org/","holds":"The largest philanthropic funder of prostate cancer research (>$1 billion), Challenge Awards and Young Investigator programme, the PCF-VA Precision Oncology Program, patient guides, and the annual Scientific Retreat.","license":"Copyright PCF","maintainer":"PCF","route":"/collections/prostate-cancer-foundation/"}
{"id":"src-snmmi","kind":"collection","name":"SNMMI Annual Meeting","aka":[],"tldr":"The SNMMI Annual Meeting, held each June by the Society of Nuclear Medicine and Molecular Imaging, is where new PET tracers, radioligand therapy results and dosimetry work are first presented. Abstracts are free as a Journal of Nuclear Medicine supplement, and that journal carries the field's papers through the rest of the year.","summary":"The SNMMI Annual Meeting is the theranostics meeting, held each June by the Society of Nuclear Medicine and Molecular Imaging. It holds nuclear medicine and theranostics content: new tracers, radioligand therapy data and dosimetry. Abstracts are free as a Journal of Nuclear Medicine supplement, and that journal carries the field's papers through the rest of the year. On Nuclide it is tagged source and congress, and it is linked from the journal record Journal of Nuclear Medicine and the institution record Society of Nuclear Medicine and Molecular Imaging.","asOf":"2026-09-08","links":[{"label":"SNMMI Annual Meeting","url":"https://www.snmmi.org/"}],"tags":["source","congress"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"url":"https://www.snmmi.org/","holds":"Nuclear medicine and theranostics: new tracers, radioligand therapy data, dosimetry.","license":"Abstracts free (Journal of Nuclear Medicine supplement)","maintainer":"Society of Nuclear Medicine and Molecular Imaging","route":"/collections/src-snmmi/"}
{"id":"src-urotoday","kind":"collection","name":"UroToday","aka":[],"tldr":"UroToday is the prostate, bladder, and kidney cancer feed, including PSMA and radioligand news.","summary":"UroToday is the daily feed for prostate, bladder and kidney cancer, holding genitourinary oncology abstracts, conference coverage and expert video, including PSMA and radioligand news. It is published by Digital Science Press and is free with registration. Its conference coverage of ASCO GU, EAU, AUA and the PSMA conference is exhaustive, which makes it the quickest way to follow a genitourinary meeting without attending. On Nuclide it is listed as a source with the tags source and news, read for the genitourinary cancers and for radioligand therapy news.","asOf":"2026-09-08","links":[{"label":"UroToday","url":"https://www.urotoday.com/"}],"tags":["source","news"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://www.urotoday.com/","holds":"Genitourinary oncology abstracts, conference coverage, and expert video.","license":"Free with registration","maintainer":"Digital Science Press","route":"/collections/src-urotoday/"}
{"id":"tcia","kind":"collection","name":"The Cancer Imaging Archive (TCIA)","aka":[],"tldr":"The public archive of cancer scans that most radiology AI is trained and tested on.","summary":"The Cancer Imaging Archive (TCIA) holds de-identified cancer imaging, CT, MRI, PET and pathology, linked to TCGA and to clinical trials, and it is the main training and testing source for radiology AI models. It has over 200 collections, pairs with TCGA genomics for radiogenomics, and is accessed through the NBIA portal and the Imaging Data Commons. TCIA is run by the NCI with the University of Arkansas; most collections are CC BY, with terms set per collection. On Nuclide it is tagged data, linked to the technology AI in radiology and the institution National Cancer Institute (NIH), and cited by the idea One certified open-source de-identification pipeline for scans and slides.","asOf":"2026-09-08","links":[{"label":"The Cancer Imaging Archive (TCIA)","url":"https://www.cancerimagingarchive.net"}],"tags":["data"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://www.cancerimagingarchive.net","holds":"De-identified cancer imaging (CT, MRI, PET, pathology) linked to TCGA and clinical trials; the main training source for radiology models.","license":"Mostly CC BY; per-collection","maintainer":"NCI / University of Arkansas","route":"/collections/tcia/"}
{"id":"chris-parker","kind":"person","name":"Chris C. Parker","aka":[],"tldr":"London radiation oncologist who led ALSYMPCA, the trial that showed radium-223 lengthens survival in prostate cancer that has spread to bone, and RADICALS-RT, which showed radiotherapy after prostatectomy can safely wait until the PSA rises.","summary":"Chris Parker is a clinical oncologist at The Royal Marsden and The Institute of Cancer Research. He was first author of the 2013 New England Journal of Medicine report of ALSYMPCA, in which the alpha-emitter radium-223 improved overall survival in castration-resistant prostate cancer with bone metastases, and of the 2020 Lancet report of RADICALS-RT, which found that early salvage radiotherapy on PSA rise was as good as adjuvant radiotherapy after prostatectomy, with less toxicity.","asOf":"2026-09-18","links":[],"tags":["prostate","radiotherapy","trialist"],"related":["ra-223"],"indications":["prostate-mcrpc","prostate-bcr","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["royal-marsden"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":[],"role":"Clinical oncologist, The Royal Marsden and The Institute of Cancer Research","institutionId":"royal-marsden","specialisms":["Prostate radiotherapy","Radium-223","Post-prostatectomy radiotherapy"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Parker%5BAuthor%5D"}],"papers":[{"title":"ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases","journal":"New England Journal of Medicine","year":2013,"url":"https://doi.org/10.1056/NEJMoa1213755","doi":"10.1056/NEJMoa1213755"},{"title":"RADICALS-RT: timing of radiotherapy after radical prostatectomy","journal":"The Lancet","year":2020,"url":"https://doi.org/10.1016/S0140-6736(20)31553-1","doi":"10.1016/S0140-6736(20)31553-1"}],"route":"/people/chris-parker/"}
{"id":"clemens-kratochwil","kind":"person","name":"Clemens Kratochwil","aka":[],"tldr":"Clemens Kratochwil reported the first patients treated with actinium-225 PSMA therapy.","summary":"Clemens Kratochwil is a nuclear medicine physician at Heidelberg University Hospital, working within the NCT and DKFZ network. His specialisms are targeted alpha therapy, PSMA radioligands and dosimetry in prostate cancer. He reported the first patients treated with actinium-225 PSMA therapy, published in the Journal of Nuclear Medicine as 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer. That first clinical experience launched the alpha-emitter era in prostate cancer, and he continues to work on actinium-225 PSMA agents and their dosimetry. His publications are listed on PubMed.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Kratochwil%20C%5BAuthor%5D%20225Ac%20PSMA"}],"tags":[],"related":["ac-225"],"indications":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["psma"],"drugs":["ac225-psma"],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"role":"Nuclear medicine physician, Heidelberg University Hospital","institutionId":"heidelberg-nct","specialisms":["Targeted alpha therapy","PSMA radioligands","Dosimetry"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Kratochwil%20C%5BAuthor%5D%20225Ac%20PSMA"}],"papers":[{"title":"225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer","journal":"Journal of Nuclear Medicine","year":2016,"doi":"10.2967/jnumed.116.178673"}],"orcid":"0000-0003-1334-8260","route":"/people/clemens-kratochwil/"}
{"id":"declan-murphy","kind":"person","name":"Declan G. Murphy","aka":[],"tldr":"Urologist who co-led proPSMA, the trial that showed PSMA PET should replace CT and bone scan for staging prostate cancer.","summary":"Declan Murphy was co-principal investigator of proPSMA, the randomised trial showing PSMA PET-CT is 27% more accurate than conventional imaging for staging high-risk prostate cancer, the evidence behind PSMA PET's adoption in guidelines. He directs GU oncology at Peter Mac, leads robotic surgery, and chairs the ANZUP theranostics and surgical sub-committees.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Murphy%20DG%5BAuthor%5D%20PSMA%20prostate"}],"tags":["prostate","imaging","surgery"],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":[],"companies":[],"institutions":["peter-mac","anzup"],"pathways":[],"terms":[],"trials":["propsma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"role":"Director of Genitourinary Oncology, Peter MacCallum Cancer Centre","institutionId":"peter-mac","specialisms":["Urological surgery","PSMA PET","Robotic prostatectomy","Prostate cancer staging"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Murphy%20DG%5BAuthor%5D%20PSMA%20prostate"}],"papers":[{"title":"Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA)","journal":"Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7"},{"title":"Prostate-specific membrane antigen positron emission tomography (PSMA-PET) for local staging of prostate cancer: a systematic review and meta-analysis","journal":"European Urology","year":2020}],"orcid":"0000-0002-7500-5899","route":"/people/declan-murphy/"}
{"id":"ebrahim-delpassand","kind":"person","name":"Ebrahim S. Delpassand","aka":[],"tldr":"The nuclear medicine physician who founded and leads Excel Diagnostics in Houston, a radiopharmaceutical therapy centre that also runs early trials of new radioligands.","summary":"Ebrahim Delpassand is Chief Executive Officer and medical director of Excel Diagnostics and Nuclear Oncology Center in Houston, which its site describes as a Radiopharmaceutical Therapy Center of Excellence designated by the Society of Nuclear Medicine and Molecular Imaging, offering PET-CT and other imaging, radionuclide therapy and clinical trials. He has been an investigator on early trials of somatostatin and PSMA radioligands. His publications are listed on PubMed.","asOf":"2026-09-17","links":[{"label":"Excel Diagnostics","url":"https://www.exceldiagnostics.com/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Delpassand+ES%5BAuthor%5D"}],"tags":["leadership"],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":["excel-diagnostics-nuclear-oncology"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chief Executive Officer and Medical Director, Excel Diagnostics and Nuclear Oncology Center","institutionId":"excel-diagnostics-nuclear-oncology","specialisms":["Nuclear medicine","Radiopharmaceutical therapy","Molecular imaging","Radiopharmaceutical trials"],"profiles":[{"label":"Excel Diagnostics","url":"https://www.exceldiagnostics.com/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Delpassand+ES%5BAuthor%5D"}],"papers":[],"route":"/people/ebrahim-delpassand/"}
{"id":"emily-bergsland","kind":"person","name":"Emily K. Bergsland","aka":[],"tldr":"Neuroendocrine tumour specialist who helps design the trials that set treatment for these rare cancers.","summary":"Emily Bergsland is Professor of Medicine and Associate Director for Education at the UCSF Helen Diller Family Comprehensive Cancer Center. A medical oncologist focused on gastroenteropancreatic neuroendocrine tumours, she chaired the Alliance A021202 trial of pazopanib versus placebo in progressive carcinoid tumours and co-authors national neuroendocrine tumour treatment guidelines. Her papers include NCCN guidance on the management of advanced gastroenteropancreatic neuroendocrine tumours, a review of systemic therapies for advanced gastrointestinal carcinoid tumours and the A021202 trial report. Her record links to lutetium-177 dotatate, somatostatin receptor 2 and VEGF-directed therapy, and she leads UCSF's cancer education programmes.","asOf":"2026-09-08","links":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Emily%20K.%20Bergsland"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Bergsland%20EK%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Emily%20K.%20Bergsland"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Medicine; Associate Director for Education, UCSF Helen Diller Family Comprehensive Cancer Center","institutionId":"ucsf","specialisms":["Neuroendocrine tumours","Gastrointestinal oncology","Clinical trials"],"profiles":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Emily%20K.%20Bergsland"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Bergsland%20EK%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Emily%20K.%20Bergsland"}],"papers":[{"title":"Management of Advanced Gastroenteropancreatic Neuroendocrine Tumors","journal":"Journal of the National Comprehensive Cancer Network","year":2025,"url":"https://doi.org/10.6004/jnccn.2025.5012","doi":"10.6004/jnccn.2025.5012"},{"title":"Systemic Therapies for Advanced Gastrointestinal Carcinoid Tumors","journal":"Hematology/Oncology Clinics of North America","year":2016,"url":"https://doi.org/10.1016/j.hoc.2015.09.002","doi":"10.1016/j.hoc.2015.09.002"},{"title":"Prospective randomized phase II trial of pazopanib versus placebo in patients with progressive carcinoid tumors (Alliance A021202)","journal":"Journal of Clinical Oncology (ASCO Annual Meeting abstract)","year":2019,"url":"https://doi.org/10.1200/JCO.2019.37.15_suppl.4005","doi":"10.1200/JCO.2019.37.15_suppl.4005"}],"route":"/people/emily-bergsland/"}
{"id":"frederik-giesel","kind":"person","name":"Frederik Giesel","aka":[],"tldr":"Frederik Giesel co-developed FAPI PET imaging and now leads nuclear medicine in Düsseldorf.","summary":"Frederik Giesel is Director of Nuclear Medicine at University Hospital Düsseldorf, having previously worked at Heidelberg University Hospital within the NCT and DKFZ network. His specialisms are molecular imaging, FAPI PET and PSMA theranostics. He co-led the first-in-human FAPI PET studies in Heidelberg, and his Journal of Nuclear Medicine paper reported the biodistribution and preliminary dosimetry of two DOTA-containing FAP-targeting agents imaged with 68Ga-FAPI PET/CT. He continues to develop FAP-targeted imaging and therapy in Düsseldorf. His publications are listed on PubMed.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Giesel%20FL%5BAuthor%5D%20FAPI"}],"tags":[],"related":["ga-68"],"indications":[],"sections":[],"technologies":["fapi-pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"role":"Director of Nuclear Medicine, University Hospital Düsseldorf; formerly Heidelberg","institutionId":"heidelberg-nct","specialisms":["Molecular imaging","FAPI PET","PSMA theranostics"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Giesel%20FL%5BAuthor%5D%20FAPI"}],"papers":[{"title":"68Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents","journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.118.215913"}],"route":"/people/frederik-giesel/"}
{"id":"hofman-michael","kind":"person","name":"Michael Hofman","aka":[],"tldr":"Led proPSMA and TheraP, the trials that proved PSMA PET beats conventional imaging and that lutetium-PSMA beats chemotherapy.","summary":"Michael Hofman is Professor of Nuclear Medicine and Director of the Prostate Cancer Theranostics and Imaging Centre of Excellence at the Peter MacCallum Cancer Centre in Melbourne. He led proPSMA, which proved that PSMA PET-CT beats conventional imaging for staging high-risk prostate cancer before curative-intent surgery or radiotherapy, and TheraP, the ANZUP trial that showed lutetium-177 PSMA-617 beats cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer. His publications include the proPSMA and TheraP reports, and his trials made Australia a global centre of theranostics. He now leads trials of earlier-line and combination radioligand therapy.","asOf":"2026-09-08","links":[{"label":"Peter MacCallum Cancer Centre","url":"https://www.petermac.org"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Hofman%20MS%5BAuthor%5D%20PSMA"}],"tags":[],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["peter-mac"],"pathways":[],"terms":[],"trials":["propsma","therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Nuclear Medicine; Director, Prostate Cancer Theranostics and Imaging Centre of Excellence","institutionId":"peter-mac","specialisms":["Theranostics","PSMA PET","Lutetium-PSMA therapy","Nuclear medicine"],"profiles":[{"label":"Peter MacCallum Cancer Centre","url":"https://www.petermac.org"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Hofman%20MS%5BAuthor%5D%20PSMA"}],"papers":[{"title":"Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA)","journal":"Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7"},{"title":"[177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP)","journal":"Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00237-3"}],"orcid":"0000-0001-8622-159X","route":"/people/hofman-michael/"}
{"id":"jason-lewis","kind":"person","name":"Jason S. Lewis","aka":[],"tldr":"Radiochemist who built the zirconium-89 immuno-PET platform and MSKCC's radiopharmaceutical pipeline.","summary":"Jason Lewis developed methods for labelling antibodies with zirconium-89 that made immuno-PET a clinical reality, including 89Zr-trastuzumab and 89Zr-J591 PSMA imaging, and leads a laboratory translating new radiotracers and radioligand therapies from chemistry to first-in-human trials. He directs radiochemistry at MSKCC and has trained many of the field's leaders.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lewis%20JS%5BAuthor%5D%20zirconium-89%20PET"}],"tags":["radiochemistry","immuno-pet","theranostics"],"related":["zr-89"],"indications":[],"sections":[],"technologies":["immuno-pet","her2-pet","radioligand-therapy"],"targets":["her2","psma"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"role":"Emily Tow Jackson Chair in Oncology and Chief Attending, Radiochemistry and Imaging Sciences Service, Memorial Sloan Kettering Cancer Center","institutionId":"mskcc","specialisms":["Radiochemistry","Immuno-PET","Radiopharmaceutical development","Targeted radiotherapy"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lewis%20JS%5BAuthor%5D%20zirconium-89%20PET"}],"papers":[{"title":"89Zr-DFO-J591 for immunoPET of prostate-specific membrane antigen expression in vivo","journal":"Journal of Nuclear Medicine","year":2010,"doi":"10.2967/jnumed.110.077982"},{"title":"Immuno-PET of HER2-positive breast cancer with 89Zr-trastuzumab: a first-in-human study","journal":"Journal of Nuclear Medicine","year":2016}],"route":"/people/jason-lewis/"}
{"id":"jeremie-calais","kind":"person","name":"Jeremie Calais","aka":[],"tldr":"Runs the UCLA theranostics trials that test PSMA imaging against conventional scans and lutetium against chemotherapy.","summary":"Jeremie Calais is Associate Professor and Director of the Clinical Research Program in the Ahmanson Translational Theranostics Division at UCLA, part of the UCLA Jonsson Comprehensive Cancer Center. A nuclear medicine physician specialising in PSMA PET and radioligand therapy, he leads prospective PSMA PET and PSMA radioligand therapy trials, including the head-to-head comparison of PSMA PET with fluciclovine PET and dosimetry research. His papers include the Lancet Oncology comparative imaging trial of 18F-fluciclovine and 68Ga-PSMA-11 PET-CT in early biochemical recurrence after prostatectomy and the Journal of Nuclear Medicine RESIST-PC phase 2 trial of 177Lu-PSMA-617 in the UCLA cohort. His work centres on prostate cancer theranostics.","asOf":"2026-09-08","links":[{"label":"UCLA profile","url":"https://www.uclahealth.org/providers?q=Jeremie%20Calais"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Calais%20J%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Jeremie%20Calais"}],"tags":[],"related":["f-18","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":["ucla-jonsson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"role":"Associate Professor; Director, Clinical Research Program, Ahmanson Translational Theranostics Division, UCLA","institutionId":"ucla-jonsson","specialisms":["PSMA PET","Radioligand therapy","Clinical trials"],"profiles":[{"label":"UCLA profile","url":"https://www.uclahealth.org/providers?q=Jeremie%20Calais"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Calais%20J%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Jeremie%20Calais"}],"papers":[{"title":"18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial","journal":"Lancet Oncology","year":2019,"url":"https://doi.org/10.1016/s1470-2045(19)30415-2","doi":"10.1016/s1470-2045(19)30415-2"},{"title":"Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with (177)Lu-PSMA-617 for metastatic castration-reSISTant Prostate Cancer (RESIST-PC): efficacy results of the UCLA cohort","journal":"Journal of Nuclear Medicine","year":2021,"url":"https://doi.org/10.2967/jnumed.121.261982","doi":"10.2967/jnumed.121.261982"}],"route":"/people/jeremie-calais/"}
{"id":"johannes-czernin","kind":"person","name":"Johannes Czernin","aka":[],"tldr":"Nuclear medicine leader who helped bring PSMA PET and radioligand therapy to the United States.","summary":"Johannes Czernin is Chief of the Ahmanson Translational Theranostics Division at UCLA, within the UCLA Jonsson Comprehensive Cancer Center, and editor-in-chief of the Journal of Nuclear Medicine. A nuclear medicine physician specialising in PSMA theranostics and PET imaging, he co-led the UCLA and UCSF prospective PSMA PET trials behind FDA approval and the US experience with 177Lu-PSMA-617, now known as lutetium-177 vipivotide tetraxetan. His papers include the JAMA Oncology prospective single-arm trial assessing 68Ga-PSMA-11 PET accuracy in localising recurrent prostate cancer and an Annual Review of Medicine article on molecular imaging in the development of cancer therapeutics. He helped bring PSMA PET and radioligand therapy to the United States.","asOf":"2026-09-08","links":[{"label":"UCLA profile","url":"https://www.uclahealth.org/providers?q=Johannes%20Czernin"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Czernin%20J%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Johannes%20Czernin"}],"tags":[],"related":["ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy","pet"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["ucla-jonsson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chief, Ahmanson Translational Theranostics Division, UCLA","institutionId":"ucla-jonsson","specialisms":["Nuclear medicine","PSMA theranostics","PET imaging"],"profiles":[{"label":"UCLA profile","url":"https://www.uclahealth.org/providers?q=Johannes%20Czernin"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Czernin%20J%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Johannes%20Czernin"}],"papers":[{"title":"Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial","journal":"JAMA Oncology","year":2019,"url":"https://doi.org/10.1001/jamaoncol.2019.0096","doi":"10.1001/jamaoncol.2019.0096"},{"title":"Molecular imaging in the development of cancer therapeutics","journal":"Annual Review of Medicine","year":2006,"url":"https://doi.org/10.1146/annurev.med.57.080904.190431","doi":"10.1146/annurev.med.57.080904.190431"}],"route":"/people/johannes-czernin/"}
{"id":"jonathan-strosberg","kind":"person","name":"Jonathan R. Strosberg","aka":[],"tldr":"Led NETTER-1, the trial that made lutetium dotatate the first approved radioligand therapy for neuroendocrine tumours.","summary":"Jonathan Strosberg was principal investigator of NETTER-1, which showed 177Lu-DOTATATE reduces the risk of progression by 79% in midgut neuroendocrine tumours and led to Lutathera's approval, the first radioligand therapy approved for a solid tumour and the template for PSMA-targeted therapy. He co-leads the NETTER-2 and COMPETE programmes and chairs the North American Neuroendocrine Tumor Society guidelines.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Strosberg%20J%5BAuthor%5D%20neuroendocrine%20lutetium"}],"tags":["neuroendocrine","radioligand","trialist"],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["compete"],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"role":"Section Head, Neuroendocrine Tumor Program, Moffitt Cancer Center","specialisms":["Neuroendocrine tumours","Peptide receptor radionuclide therapy","Somatostatin analogues","Radioligand trials"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Strosberg%20J%5BAuthor%5D%20neuroendocrine%20lutetium"}],"papers":[{"title":"Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors (NETTER-1)","journal":"NEJM","year":2017,"doi":"10.1056/NEJMoa1607427"},{"title":"177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results","journal":"Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00572-6"},{"title":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","journal":"The Lancet","year":2024,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"}],"route":"/people/jonathan-strosberg/"}
{"id":"karim-fizazi","kind":"person","name":"Karim Fizazi","aka":[],"tldr":"Led LATITUDE and PEACE-1, which put abiraterone into first-line metastatic prostate cancer.","summary":"Karim Fizazi is Head of Medical Oncology at Gustave Roussy and Professor at Paris-Saclay, with links to Centre Oscar Lambret. His specialisms are prostate cancer, genitourinary oncology, hormone therapy and radioligand therapy. He is one of the most influential prostate cancer trialists of the past two decades, leading LATITUDE, the New England Journal of Medicine trial of abiraterone plus prednisone in high-risk metastatic castration-sensitive prostate cancer, and PEACE-1, the Lancet trial adding abiraterone to androgen deprivation therapy and docetaxel in de novo metastatic disease. He has also led studies of radium-223 and PSMA radioligands, and is linked to the ALSYMPCA trial. His publications are listed on PubMed.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Fizazi%20K%5BAuthor%5D%20prostate%20abiraterone"}],"tags":[],"related":["ra-223"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","radium-223"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Head of Medical Oncology, Gustave Roussy; Professor, Paris-Saclay","specialisms":["Prostate cancer","Genitourinary oncology","Hormone therapy","Radioligand therapy"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Fizazi%20K%5BAuthor%5D%20prostate%20abiraterone"}],"papers":[{"title":"Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer (LATITUDE)","journal":"NEJM","year":2017,"doi":"10.1056/NEJMoa1704174"},{"title":"Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1)","journal":"Lancet","year":2022,"doi":"10.1016/S0140-6736(22)00367-1"},{"title":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","journal":"New England Journal of Medicine","year":2021,"url":"https://doi.org/10.1056/NEJMoa2107322","doi":"10.1056/NEJMoa2107322"},{"title":"ARAMIS: darolutamide in non-metastatic castration-resistant prostate cancer","journal":"New England Journal of Medicine","year":2019,"url":"https://doi.org/10.1056/NEJMoa1815671","doi":"10.1056/NEJMoa1815671"}],"route":"/people/karim-fizazi/"}
{"id":"katherine-matthay","kind":"person","name":"Katherine K. Matthay","aka":[],"tldr":"Paediatric oncologist whose trials established transplant and 13-cis-retinoic acid for high-risk neuroblastoma.","summary":"Katherine Matthay is Professor Emerita of Pediatrics at UCSF, within the UCSF Helen Diller Family Comprehensive Cancer Center, and a neuroblastoma investigator with the Children's Oncology Group (COG). A paediatric oncologist and long-time chair of COG neuroblastoma studies, she led the CCG-3891 trial establishing myeloablative therapy and 13-cis-retinoic acid in high-risk neuroblastoma and pioneered 131I-MIBG therapy for relapsed disease. Her papers report the Children's Cancer Group trial of intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cis-retinoic acid, and the long-term results of that randomised trial. Her work links iobenguane I-131 and radioligand therapy to paediatric neuroblastoma.","asOf":"2026-09-08","links":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Katherine%20K.%20Matthay"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Matthay%20KK%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Katherine%20K.%20Matthay"}],"tags":[],"related":["i-131"],"indications":["neuroblastoma"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor Emerita of Pediatrics, UCSF; Children's Oncology Group neuroblastoma investigator","institutionId":"ucsf","specialisms":["Paediatric oncology","Neuroblastoma","MIBG therapy"],"profiles":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Katherine%20K.%20Matthay"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Matthay%20KK%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Katherine%20K.%20Matthay"}],"papers":[{"title":"Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group","journal":"New England Journal of Medicine","year":1999,"url":"https://doi.org/10.1056/NEJM199910143411601","doi":"10.1056/NEJM199910143411601"},{"title":"Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study","journal":"Journal of Clinical Oncology","year":2009,"url":"https://doi.org/10.1200/JCO.2007.13.8925","doi":"10.1200/JCO.2007.13.8925"}],"route":"/people/katherine-matthay/"}
{"id":"ken-herrmann","kind":"person","name":"Ken Herrmann","aka":[],"tldr":"Nuclear medicine leader who co-led VISION and runs one of the world's largest theranostics programmes.","summary":"Ken Herrmann was a lead investigator of VISION and of the German multicentre 177Lu-PSMA-617 registry, and leads the Essen theranostics centre that has treated thousands of patients with PSMA and somatostatin receptor radioligands. He has chaired the EANM oncology committee, co-authored the Lancet Oncology series on theranostics, and leads trials of alpha emitters and new targets such as FAP.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Herrmann%20K%5BAuthor%5D%20theranostics%20PSMA"}],"tags":["radioligand","nuclear-medicine","germany"],"related":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","psma-pet","fapi-pet"],"targets":["psma","fap"],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":["essen-wtz","eanm"],"pathways":[],"terms":[],"trials":["vision"],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"role":"Chair of Nuclear Medicine, University Hospital Essen","institutionId":"essen-wtz","specialisms":["Theranostics","PSMA radioligand therapy","Nuclear medicine","Radiopharmaceutical trials"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Herrmann%20K%5BAuthor%5D%20theranostics%20PSMA"}],"papers":[{"title":"Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer (VISION)","journal":"NEJM","year":2021,"doi":"10.1056/NEJMoa2107322"},{"title":"Radiotheranostics: a roadmap for future development","journal":"Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(19)30821-6"}],"orcid":"0000-0002-9662-7259","route":"/people/ken-herrmann/"}
{"id":"louise-emmett","kind":"person","name":"Louise Emmett","aka":[],"tldr":"Nuclear medicine physician who leads ENZA-p and the PSMA imaging trials shaping Australian theranostics.","summary":"Louise Emmett (St Vincent's Hospital, Sydney) was principal investigator of ENZA-p, the ANZUP trial showing that adding 177Lu-PSMA-617 to enzalutamide delays progression in castration-resistant prostate cancer, and led the PRIMARY study of PSMA PET for diagnosis. She co-leads the ANZUP theranostics programme and writes widely used guidance on PSMA PET reporting.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Emmett%20L%5BAuthor%5D%20PSMA"}],"tags":["prostate","radioligand","australia"],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"role":"Director of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney; Professor, UNSW","specialisms":["PSMA theranostics","Nuclear medicine","Prostate cancer imaging","Radioligand trials"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Emmett%20L%5BAuthor%5D%20PSMA"}],"papers":[{"title":"[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial","journal":"Lancet Oncology","year":2024},{"title":"The additive diagnostic value of prostate-specific membrane antigen positron emission tomography computed tomography to multiparametric magnetic resonance imaging triage in the diagnosis of prostate cancer (PRIMARY)","journal":"European Urology","year":2021,"doi":"10.1016/j.eururo.2021.08.002"}],"orcid":"0000-0002-4895-7384","route":"/people/louise-emmett/"}
{"id":"michael-morris","kind":"person","name":"Michael J. Morris","aka":[],"tldr":"Principal investigator of the VISION trial that made lutetium-PSMA a standard prostate cancer treatment.","summary":"Michael J. Morris is Prostate Cancer Section Head on the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center. He is a medical oncologist known as principal investigator of the VISION trial, which made lutetium-177 PSMA radioligand therapy a standard prostate cancer treatment, and co-led PSMAfore and PSMA PET studies. His selected papers report lutetium-177 PSMA-617 for metastatic castration-resistant prostate cancer and the PSMAfore comparison against a change of androgen receptor pathway inhibitor in taxane-naive patients. He chaired the Alliance genitourinary committee and focuses on radioligand therapy and imaging biomarkers.","asOf":"2026-09-08","links":[{"label":"MSK profile","url":"https://www.mskcc.org/cancer-care/doctors/michael-morris"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Morris%20MJ%5BAuthor%5D"}],"tags":[],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":["vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Prostate Cancer Section Head, Genitourinary Oncology Service","institutionId":"mskcc","specialisms":["Prostate cancer","Radiopharmaceuticals","PSMA theranostics"],"profiles":[{"label":"MSK profile","url":"https://www.mskcc.org/cancer-care/doctors/michael-morris"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Morris%20MJ%5BAuthor%5D"}],"papers":[{"title":"Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer","journal":"New England Journal of Medicine","year":2021,"url":"https://doi.org/10.1056/NEJMoa2107322","doi":"10.1056/NEJMoa2107322"},{"title":"177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore)","journal":"Lancet","year":2024,"url":"https://doi.org/10.1016/S0140-6736(24)01653-2","doi":"10.1016/S0140-6736(24)01653-2"}],"route":"/people/michael-morris/"}
{"id":"oliver-sartor","kind":"person","name":"A. Oliver Sartor","aka":[],"tldr":"Led VISION, the trial that made lutetium-PSMA the first radioligand therapy for prostate cancer.","summary":"Oliver Sartor was co-principal investigator of VISION, which showed 177Lu-PSMA-617 improves survival in PSMA-positive metastatic castration-resistant prostate cancer and led to Pluvicto's approval, and was a lead investigator of PSMAfore, which moved the therapy before chemotherapy. He also co-led ALSYMPCA (radium-223). He directs the radiopharmaceutical trials programme at Mayo Clinic.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Oliver_Sartor","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sartor%20O%5BAuthor%5D%20PSMA%20lutetium"}],"tags":["prostate","radioligand","trialist"],"related":["lu-177","ra-223"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":[],"trials":["vision","psmafore","alsympca"],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Medical Oncology and Urology, Mayo Clinic","institutionId":"mayo-clinic","specialisms":["Prostate cancer","Radioligand therapy","PSMA-targeted therapy","Radium-223"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sartor%20O%5BAuthor%5D%20PSMA%20lutetium"}],"papers":[{"title":"Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer (VISION)","journal":"NEJM","year":2021,"doi":"10.1056/NEJMoa2107322"},{"title":"Alpha emitter radium-223 and survival in metastatic prostate cancer (ALSYMPCA)","journal":"NEJM","year":2013,"doi":"10.1056/NEJMoa1213755"}],"route":"/people/oliver-sartor/"}
{"id":"paola-anna-erba","kind":"person","name":"Paola Anna Erba","aka":[],"tldr":"Italian nuclear medicine physician serving as President of the European Association of Nuclear Medicine.","summary":"Paola Anna Erba is President of the European Association of Nuclear Medicine (EANM) for the 2025-2026 term. She is a nuclear medicine physician and academic in Italy whose research covers molecular imaging, radioligand therapy and infection and inflammation imaging. As EANM President she leads the society's congress, guidelines and advocacy for nuclear medicine in oncology.","asOf":"2026-09-10","links":[{"label":"Society page","url":"https://eanm.org/the-eanm-community/organisation/board/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Erba+PA%5BAuthor%5D"}],"tags":["leadership","clinician-scientist","nuclear medicine","theranostics"],"related":[],"indications":["neuroendocrine","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["eanm"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"President (2025-2026)","institutionId":"eanm","specialisms":["Nuclear medicine","Theranostics","Molecular imaging"],"profiles":[{"label":"Society page","url":"https://eanm.org/the-eanm-community/organisation/board/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Erba+PA%5BAuthor%5D"}],"papers":[{"title":"[18F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results","journal":"Radiation Oncology","year":2016,"doi":"10.1186/s13014-016-0586-x"},{"title":"Artificial intelligence and hybrid imaging: the best match for personalized medicine in oncology","journal":"European Journal of Hybrid Imaging","year":2020,"doi":"10.1186/s41824-020-00094-8"},{"title":"Differentiated Thyroid Cancer: A New Perspective with Radiolabeled Somatostatin Analogues for Imaging and Treatment of Patients","journal":"Thyroid®","year":2014,"doi":"10.1089/thy.2013.0225"}],"route":"/people/paola-anna-erba/"}
{"id":"peter-bartenstein","kind":"person","name":"Peter Bartenstein","aka":[],"tldr":"Peter Bartenstein is a nuclear medicine head whose department is a leading European PSMA theranostics centre.","summary":"Peter Bartenstein is Director of the Department of Nuclear Medicine at LMU Klinikum München. His specialisms are nuclear medicine, PSMA theranostics and neuro-imaging. His department is a leading European centre for PSMA PET and lutetium-177 PSMA radioligand therapy, and it co-developed 177Lu-PSMA-I&T. His papers include a dosimetry study of 177Lu-DKFZ-PSMA-617 as a new radiopharmaceutical for metastatic prostate cancer, the first clinical results of 18F-SiFAlin-TATE PET for imaging neuroendocrine tumours, and a European Urology study showing that 68Ga-PSMA PET/CT accurately stages lymph node regions before dissection in prostate cancer. His publications are listed on PubMed.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Bartenstein%20P%5BAuthor%5D%20PSMA"}],"tags":[],"related":["f-18","ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":["lu177-psma-it"],"companies":[],"institutions":["lmu-munich"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Director, Department of Nuclear Medicine, LMU Munich","institutionId":"lmu-munich","specialisms":["Nuclear medicine","PSMA theranostics","Neuro-imaging"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Bartenstein%20P%5BAuthor%5D%20PSMA"}],"papers":[{"title":"Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2015,"doi":"10.1007/s00259-015-3174-7"},{"title":"Biodistribution and first clinical results of 18F-SiFAlin-TATE PET: a novel 18F-labeled somatostatin analog for imaging of neuroendocrine tumors","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2019,"doi":"10.1007/s00259-019-04501-6"},{"title":"68Ga-PSMA Positron Emission Tomography/Computed Tomography Provides Accurate Staging of Lymph Node Regions Prior to Lymph Node Dissection in Patients with Prostate Cancer","journal":"European Urology","year":2016,"doi":"10.1016/j.eururo.2015.12.051"}],"route":"/people/peter-bartenstein/"}
{"id":"pierre-vera","kind":"person","name":"Pierre Vera","aka":[],"tldr":"Nuclear medicine physician who directs Centre Henri Becquerel, the comprehensive cancer centre for the Rouen area in Normandy.","summary":"Professeur Pierre Vera is Directeur Général of Centre Henri Becquerel, the Centre de Lutte Contre le Cancer in Rouen. He is a nuclear medicine physician, and the centre's organisation page records his appointment to a five-year term beginning in 2017. He works with Artus Paty, Directeur Général Adjoint, who has been at the centre since 2016, supported by a Comité de Direction (CODIR) and a Conférence Médicale d'Etablissement (CME). The centre is overseen by a board of directors chaired by a representative of the State.","asOf":"2026-09-10","links":[{"label":"Source: Centre Henri Becquerel organisation page","url":"https://www.becquerel.fr/le-centre/decouvrir-le-centre/organisation/"}],"tags":["leadership","clinician-scientist","comprehensive-cancer-centre"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"role":"Directeur Général (Director General), Centre Henri Becquerel","specialisms":["Nuclear medicine","Cancer imaging","Cancer centre management"],"profiles":[{"label":"Centre Henri Becquerel organisation page","url":"https://www.becquerel.fr/le-centre/decouvrir-le-centre/organisation/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Vera+P%5BAuthor%5D+AND+Rouen"}],"papers":[{"title":"Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7–IFCT-1402): a multicentre, randomised, controlled phase 2 trial","journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00320-6"},{"title":"Radiomics: Principles and radiotherapy applications","journal":"Critical Reviews in Oncology/Hematology","year":2019,"doi":"10.1016/j.critrevonc.2019.03.015"},{"title":"Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort","journal":"Blood Cancer Journal","year":2018,"doi":"10.1038/s41408-018-0111-6"}],"route":"/people/pierre-vera/"}
{"id":"rafael-mariano-grossi","kind":"person","name":"Rafael Mariano Grossi","aka":[],"tldr":"Argentine diplomat leading the IAEA since 2019, whose Rays of Hope initiative expands radiotherapy and nuclear medicine access in low- and middle-income countries.","summary":"Rafael Mariano Grossi has been Director General of the International Atomic Energy Agency since December 2019. Under his leadership the IAEA launched Rays of Hope, an initiative to close the gap in access to radiotherapy, diagnostic imaging and nuclear medicine for cancer in countries with little or no capacity. His role is recorded in the public record.","asOf":"2026-09-10","links":[{"label":"Institution profile","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":["leadership","radiotherapy","global health"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iaea"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Director General","institutionId":"iaea","specialisms":["International diplomacy","Nuclear applications in health","Global cancer care access"],"profiles":[{"label":"Institution profile","url":"https://www.iaea.org/services/rays-of-hope"}],"papers":[{"title":"The IAEA’s Rays of Hope leverages nuclear science and collaboration to fight cancer in developing countries","journal":"Journal of Cancer Policy","year":2022,"doi":"10.1016/j.jcpo.2022.100357"}],"route":"/people/rafael-mariano-grossi/"}
{"id":"rahul-aggarwal","kind":"person","name":"Rahul Aggarwal","aka":[],"tldr":"Prostate oncologist studying how tumours transform to escape hormone therapy and how to target them with radioligands.","summary":"Rahul Aggarwal is Associate Director for Clinical Sciences at the UCSF Helen Diller Family Comprehensive Cancer Center. A medical oncologist specialising in prostate cancer, neuroendocrine prostate cancer and PSMA theranostics, he leads UCSF's early-phase and prostate cancer clinical research and defined treatment-emergent small-cell neuroendocrine prostate cancer, the way tumours transform to escape hormone therapy. His papers include a multi-institutional prospective study characterising that disease clinically and genomically, and a report on heterogeneous flare in PSMA PET tracer uptake after starting androgen pathway blockade. He leads PSMA radioligand and combination trials, including with lutetium-177 vipivotide tetraxetan.","asOf":"2026-09-08","links":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Rahul%20Aggarwal"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Aggarwal%20R%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Rahul%20Aggarwal"}],"tags":[],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Associate Director for Clinical Sciences, UCSF Helen Diller Family Comprehensive Cancer Center","institutionId":"ucsf","specialisms":["Prostate cancer","Neuroendocrine prostate cancer","PSMA theranostics"],"profiles":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Rahul%20Aggarwal"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Aggarwal%20R%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Rahul%20Aggarwal"}],"papers":[{"title":"Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study","journal":"Journal of Clinical Oncology","year":2018,"url":"https://doi.org/10.1200/JCO.2017.77.6880","doi":"10.1200/JCO.2017.77.6880"},{"title":"Heterogeneous Flare in Prostate-specific Membrane Antigen Positron Emission Tomography Tracer Uptake with Initiation of Androgen Pathway Blockade in Metastatic Prostate Cancer","journal":"European Urology Oncology","year":2018,"url":"https://doi.org/10.1016/j.euo.2018.03.010","doi":"10.1016/j.euo.2018.03.010"}],"route":"/people/rahul-aggarwal/"}
{"id":"richard-baum","kind":"person","name":"Richard P. Baum","aka":[],"tldr":"One of the pioneers of peptide receptor radionuclide therapy for neuroendocrine tumours, now practising at the Curanosticum theranostics centre in Wiesbaden.","summary":"Richard Baum is a specialist in nuclear medicine whom Curanosticum describes as one of the leading experts in therapeutic nuclear medicine and part of its medical team since 2020. The centre offers PET-CT, radioiodine therapy, PSMA radioligand therapy and DOTATOC receptor radionuclide therapy. Before Wiesbaden he built the theranostics programme at the Zentralklinik Bad Berka, where lutetium-177 and yttrium-90 labelled somatostatin analogues were used to treat thousands of patients with neuroendocrine tumours, work that preceded the approvals of lutetium-177 dotatate and lutetium-177 PSMA-617. His publications are listed on PubMed.","asOf":"2026-09-17","links":[{"label":"Curanosticum","url":"https://www.curanosticum.de/en/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Baum+RP%5BAuthor%5D+radionuclide"}],"tags":["leadership"],"related":["lu-177","y-90"],"indications":["neuroendocrine","prostate"],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":["curanosticum"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Nuclear medicine specialist, Curanosticum Wiesbaden-Frankfurt","institutionId":"curanosticum","specialisms":["Nuclear medicine","Peptide receptor radionuclide therapy","PSMA radioligand therapy","Theranostics"],"profiles":[{"label":"Curanosticum","url":"https://www.curanosticum.de/en/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Baum+RP%5BAuthor%5D+radionuclide"}],"papers":[{"title":"Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors","journal":"New England Journal of Medicine","year":2017,"url":"https://doi.org/10.1056/NEJMoa1607427","doi":"10.1056/NEJMoa1607427","note":"Europe PMC author record matched by affiliation"},{"title":"FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2010,"url":"https://doi.org/10.1007/s00259-009-1297-4","doi":"10.1007/s00259-009-1297-4","note":"Europe PMC author record matched by affiliation"},{"title":"German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients","journal":"Journal of Nuclear Medicine","year":2017,"url":"https://doi.org/10.2967/jnumed.116.183194","doi":"10.2967/jnumed.116.183194","note":"Europe PMC author record matched by affiliation"}],"route":"/people/richard-baum/"}
{"id":"robert-mach","kind":"person","name":"Robert H. Mach","aka":[],"tldr":"Robert Mach invented the PARP PET tracer FluorThanatrace that images DNA repair capacity in tumours.","summary":"Robert H. Mach is the Britton Chance Professor of Radiology and Director of PET Radiochemistry at the Abramson Cancer Center, University of Pennsylvania. He is a radiochemist known for inventing the PARP PET tracer fluorine-18 FluorThanatrace, which images DNA repair capacity in tumours, alongside other tracers for imaging drug targets. His selected paper reports FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer. His laboratory's tracers enable PARP-inhibitor patient selection studies and molecular imaging with PET.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mach%20RH%5BAuthor%5D"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["parp-pet","pet"],"targets":["parp"],"drugs":[],"companies":[],"institutions":["penn-abramson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Britton Chance Professor of Radiology; Director, PET Radiochemistry","institutionId":"penn-abramson","specialisms":["Radiochemistry","PARP PET","Molecular imaging"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mach%20RH%5BAuthor%5D"}],"papers":[{"title":"[18F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer","journal":"American Journal of Nuclear Medicine and Molecular Imaging","year":2018}],"orcid":"0000-0002-7645-2869","route":"/people/robert-mach/"}
{"id":"sandhu-shahneen","kind":"person","name":"Shahneen Sandhu","aka":[],"tldr":"Runs the medical oncology side of Peter Mac's theranostics programme, combining lutetium-PSMA with hormonal and immune therapies.","summary":"Shahneen Sandhu is a medical oncologist and Lead for Genitourinary Oncology Theranostics at the Peter MacCallum Cancer Centre in Melbourne. She runs the medical oncology side of Peter Mac's theranostics programme, leading combination trials such as PRINCE and UpFrontPSMA that pair lutetium-177 PSMA-617 with androgen receptor pathway inhibitors, chemotherapy and immunotherapy. Her publications include the UpFrontPSMA trial of sequential lutetium-177 PSMA-617 and docetaxel against docetaxel alone in metastatic hormone-sensitive prostate cancer. She also contributes to melanoma and early-phase research.","asOf":"2026-09-08","links":[{"label":"Peter MacCallum Cancer Centre","url":"https://www.petermac.org"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sandhu%20S%5BAuthor%5D%20Peter%20MacCallum%20prostate%20PSMA"}],"tags":[],"related":["lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma"],"drugs":["pluvicto"],"companies":[],"institutions":["peter-mac"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Medical oncologist; Lead, Genitourinary Oncology Theranostics, Peter Mac","institutionId":"peter-mac","specialisms":["Prostate cancer","Theranostics","Melanoma","Early-phase trials"],"profiles":[{"label":"Peter MacCallum Cancer Centre","url":"https://www.petermac.org"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sandhu%20S%5BAuthor%5D%20Peter%20MacCallum%20prostate%20PSMA"}],"papers":[{"title":"Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in metastatic hormone-sensitive prostate cancer (UpFrontPSMA)","journal":"Lancet Oncology","year":2024,"doi":"10.1016/S1470-2045(24)00440-6"}],"orcid":"0000-0002-8660-4475","route":"/people/sandhu-shahneen/"}
{"id":"silke-gillessen","kind":"person","name":"Silke Gillessen","aka":[],"tldr":"Founder and chair of the APCCC consensus conference that guides advanced prostate cancer management worldwide.","summary":"Silke Gillessen (IOSI, Bellinzona) founded the Advanced Prostate Cancer Consensus Conference, whose biennial reports are the most widely used expert guidance on managing advanced prostate cancer where trial evidence is lacking. She was a lead investigator in STAMPEDE and in trials of PSMA radioligand therapy and helped establish the Swiss Group for Clinical Cancer Research GU programme.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Gillessen%20S%5BAuthor%5D%20prostate%20consensus"}],"tags":["prostate","guidelines","switzerland"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"role":"Medical and Scientific Director, Oncology Institute of Southern Switzerland (IOSI), Bellinzona","specialisms":["Prostate cancer","Consensus guidelines","Genitourinary oncology","Treatment sequencing"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Gillessen%20S%5BAuthor%5D%20prostate%20consensus"}],"papers":[{"title":"Management of patients with advanced prostate cancer: report from the Advanced Prostate Cancer Consensus Conference 2021","journal":"European Urology","year":2022,"doi":"10.1016/j.eururo.2022.04.002"},{"title":"Abiraterone for prostate cancer not previously treated with hormone therapy (STAMPEDE)","journal":"NEJM","year":2017,"doi":"10.1056/NEJMoa1702900"}],"orcid":"0000-0001-5746-6555","route":"/people/silke-gillessen/"}
{"id":"simron-singh","kind":"person","name":"Simron Singh","aka":[],"tldr":"Led NETTER-2, which moved lutetium dotatate into first-line treatment of higher-grade neuroendocrine tumours.","summary":"Simron Singh was principal investigator of NETTER-2, which showed first-line 177Lu-DOTATATE plus octreotide dramatically improves progression-free survival over high-dose octreotide in grade 2-3 gastroenteropancreatic neuroendocrine tumours, extending radioligand therapy to newly diagnosed patients. He has led Canadian and international NET guidelines and studies of NET epidemiology and patient-reported outcomes.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Singh%20S%5BAuthor%5D%20neuroendocrine%20NETTER-2"}],"tags":["neuroendocrine","radioligand","canada"],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy"],"targets":["sstr2"],"drugs":["lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"role":"Medical Oncologist and Co-Director, Susan Leslie Clinic for Neuroendocrine Tumours, Sunnybrook Odette Cancer Centre","specialisms":["Neuroendocrine tumours","Radioligand therapy","Health services research","Guidelines"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Singh%20S%5BAuthor%5D%20neuroendocrine%20NETTER-2"}],"papers":[{"title":"[177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2)","journal":"Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00701-3"},{"title":"Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society guidelines for the diagnosis and management of patients with lung neuroendocrine tumors","journal":"Journal of Thoracic Oncology","year":2020,"doi":"10.1016/j.jtho.2020.06.021"},{"title":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","journal":"The Lancet","year":2024,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"}],"route":"/people/simron-singh/"}
{"id":"song-shaoli","kind":"person","name":"Shaoli Song","aka":[],"tldr":"Leads the nuclear medicine group behind the first human TROP2 PET imaging, aiming to pick patients for TROP2 ADCs with a scan.","summary":"Shaoli Song is Professor and Director of the Department of Nuclear Medicine at Fudan University Shanghai Cancer Center. Her department developed and imaged the first TROP2-targeted PET tracers in patients with breast and other cancers, with the aim of selecting patients for TROP2 antibody-drug conjugates using a scan, alongside FAPI, HER2 and PSMA theranostic work. Her publications include head-to-head comparisons of FDG and FAPI PET-CT in recurrent soft tissue sarcoma and in platinum-sensitive recurrent ovarian cancer, and a study of preoperative FDG PET parameters for predicting microvascular invasion and recurrence in hepatocellular carcinoma. Her interests are PET tracer development and theranostics.","asOf":"2026-09-08","links":[{"label":"Fudan University Shanghai Cancer Center","url":"https://www.shca.org.cn"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Song%20S%5BAuthor%5D%20Fudan%20TROP2%20PET"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["trop2-pet","fapi-pet","her2-pet"],"targets":["trop2","fap"],"drugs":[],"companies":[],"institutions":["fuscc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor and Director, Department of Nuclear Medicine, Fudan University Shanghai Cancer Center","institutionId":"fuscc","specialisms":["Nuclear medicine","PET tracer development","TROP2 and HER2 PET","Theranostics"],"profiles":[{"label":"Fudan University Shanghai Cancer Center","url":"https://www.shca.org.cn"},{"label":"PubMed author search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Song%20S%5BAuthor%5D%20Fudan%20TROP2%20PET"}],"papers":[{"title":"Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2022,"doi":"10.1007/s00259-022-05700-4"},{"title":"Head-to-head comparison of [18F]-FDG and [68 Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023,"doi":"10.1007/s00259-022-06096-x"},{"title":"The value of preoperative 18F-FDG PET metabolic and volumetric parameters in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma","journal":"Nuclear Medicine Communications","year":2021,"doi":"10.1097/mnm.0000000000001478"}],"route":"/people/song-shaoli/"}
{"id":"thomas-hope","kind":"person","name":"Thomas A. Hope","aka":[],"tldr":"Nuclear medicine physician who led the trials that got PSMA PET approved in the United States.","summary":"Thomas Hope is Professor of Radiology and Chief of Nuclear Medicine at UCSF, within the UCSF Helen Diller Family Comprehensive Cancer Center. A nuclear medicine physician specialising in PSMA PET and theranostics, his prospective studies of 68Ga-PSMA-11 PET at UCSF and UCLA supported the first FDA approval of PSMA PET in the United States in 2020. His papers include a JAMA Oncology multicentre prospective phase 3 imaging trial of the diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis before radical prostatectomy and a JAMA Oncology prospective single-arm trial assessing its accuracy in localising recurrent prostate cancer. He leads theranostics research and PSMA radioligand dosimetry work in prostate cancer.","asOf":"2026-09-08","links":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Thomas%20A.%20Hope"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Hope%20TA%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Thomas%20A.%20Hope"}],"tags":[],"related":["ga-68"],"indications":["prostate"],"sections":[],"technologies":["psma-pet","radioligand-therapy","pet"],"targets":["psma"],"drugs":[],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Radiology; Chief of Nuclear Medicine, UCSF","institutionId":"ucsf","specialisms":["Nuclear medicine","PSMA PET","Theranostics"],"profiles":[{"label":"UCSF profile","url":"https://profiles.ucsf.edu/search/?searchtype=people&searchfor=Thomas%20A.%20Hope"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Hope%20TA%5BAuthor%5D"},{"label":"Google Scholar","url":"https://scholar.google.com/scholar?q=Thomas%20A.%20Hope"}],"papers":[{"title":"Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial","journal":"JAMA Oncology","year":2021,"url":"https://doi.org/10.1001/jamaoncol.2021.3771","doi":"10.1001/jamaoncol.2021.3771"},{"title":"Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial","journal":"JAMA Oncology","year":2019,"url":"https://doi.org/10.1001/jamaoncol.2019.0096","doi":"10.1001/jamaoncol.2019.0096"}],"route":"/people/thomas-hope/"}
{"id":"uwe-haberkorn","kind":"person","name":"Uwe Haberkorn","aka":[],"tldr":"Nuclear medicine physician whose group invented FAPI PET tracers and pioneered PSMA and FAP radioligand therapy.","summary":"Uwe Haberkorn is Head of Nuclear Medicine at Heidelberg University Hospital and the German Cancer Research Center (DKFZ). His specialisms are nuclear medicine, FAP-targeted radiopharmaceuticals and theranostics, with a focus on the FAP and PSMA targets. His Heidelberg group invented the quinoline-based FAP inhibitor (FAPI) tracers, and his Journal of Nuclear Medicine paper reported 68Ga-FAPI PET/CT tracer uptake across 28 different kinds of cancer. The group also led early PSMA-617 and FAP-targeted radioligand therapy in humans, and his record links him to FAP-2286 and lutetium-177 vipivotide tetraxetan. His publications are listed on PubMed.","asOf":"2026-09-08","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Haberkorn%20U%5BAuthor%5D%20FAPI"}],"tags":[],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":["fapi-pet","radioligand-therapy","psma-pet"],"targets":["fap","psma"],"drugs":["fap-2286","pluvicto"],"companies":[],"institutions":["heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"role":"Head of Nuclear Medicine, Heidelberg University Hospital and DKFZ","institutionId":"heidelberg-nct","specialisms":["Nuclear medicine","FAP-targeted radiopharmaceuticals","Theranostics"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Haberkorn%20U%5BAuthor%5D%20FAPI"}],"papers":[{"title":"68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer","journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.119.227967"}],"route":"/people/uwe-haberkorn/"}
{"id":"virginia-pappas","kind":"person","name":"Virginia Pappas","aka":[],"tldr":"Long-serving CEO of the Society of Nuclear Medicine and Molecular Imaging.","summary":"Virginia Pappas is Chief Executive Officer of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the principal US professional society for nuclear medicine physicians, scientists and technologists. She leads the society's staff and operations, supporting its scientific meetings, journals and advocacy for molecular imaging and radiopharmaceutical therapy in oncology.","asOf":"2026-09-10","links":[{"label":"Society page","url":"https://www.snmmi.org/"}],"tags":["leadership","nuclear medicine"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chief Executive Officer","institutionId":"snmmi","specialisms":["Association management","Nuclear medicine advocacy"],"profiles":[{"label":"Society page","url":"https://www.snmmi.org/"}],"papers":[],"route":"/people/virginia-pappas/"}
{"id":"wolfgang-weber","kind":"person","name":"Wolfgang A. Weber","aka":[],"tldr":"Nuclear medicine physician who established PET response criteria and leads Munich's radiopharmaceutical development pipeline.","summary":"Wolfgang Weber led the early studies showing FDG-PET response after one cycle of chemotherapy predicts outcome in lung and gastro-oesophageal cancer and helped define PERCIST response criteria. He directs nuclear medicine at TUM, where PSMA ligands and FAP inhibitors were developed, and has been president of the Society of Nuclear Medicine and Molecular Imaging. His current focus is trial design for theranostics.","asOf":"2026-09-10","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Weber%20WA%5BAuthor%5D%20PET"}],"tags":["nuclear-medicine","imaging","theranostics"],"related":[],"indications":[],"sections":[],"technologies":["pet","fdg-pet","radioligand-therapy","fapi-pet"],"targets":[],"drugs":[],"companies":[],"institutions":["tum-munich","snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chair of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich","institutionId":"tum-munich","specialisms":["Molecular imaging","PET response assessment","Theranostics","Radiopharmaceutical development"],"profiles":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Weber%20WA%5BAuthor%5D%20PET"}],"papers":[{"title":"Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use","journal":"JCO","year":2003,"doi":"10.1200/JCO.2003.06.120"},{"title":"Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging","journal":"JCO","year":2001,"doi":"10.1200/JCO.2001.19.12.3058"}],"orcid":"0000-0002-7854-4345","route":"/people/wolfgang-weber/"}
{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","aka":[],"tldr":"Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.","summary":"Oncology inherited from cytotoxic chemotherapy the assumption that more drug is better, so phase 1 trials escalate to the maximum tolerated dose over a few weeks in a few dozen patients and that dose becomes the label. Targeted agents, antibodies, ADCs and immunotherapies saturate their targets far below toxicity, and chronic dosing exposes patients to months of grade 2 toxicity that the 28-day dose-limiting-toxicity window never measured. The consequences are dose reductions and discontinuations in a third or more of patients on many oral targeted agents, avoidable cost, and occasionally drugs that fail because nobody can stay on them. The FDA's Project Optimus (2021) and its 2024 guidance now require randomised comparison of at least two doses before registration, and trials such as PERSEPHONE show that duration can be halved without loss of efficacy. Dosimetry-based individualisation is the parallel challenge in radioligand therapy.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"},{"label":"Shah, Rahman, Theoret & Pazdur, The drug-dosing conundrum in oncology: when less is more (NEJM 2021)","url":"https://doi.org/10.1056/NEJMp2109826"},{"label":"Earl et al., 6 versus 12 months of adjuvant trastuzumab (PERSEPHONE, Lancet 2019)","url":"https://doi.org/10.1016/S0140-6736(19)30650-6"}],"tags":[],"related":["idea-net-dosimetry-prrt","idea-total-body-pet-dosimetry"],"indications":["breast-her2-positive","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","prrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry","alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"trials","severity":"major","metrics":[{"label":"Patients requiring dose reduction of abemaciclib for adverse events in first-line MONARCH 3","value":"~43%","source":"Goetz et al., JCO 2017","url":"https://doi.org/10.1200/JCO.2017.75.6155"},{"label":"Six vs twelve months of adjuvant trastuzumab in HER2-positive breast cancer (PERSEPHONE): 4-year disease-free survival","value":"89.4% vs 89.8% (non-inferior)","source":"Earl et al., Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)30650-6"}],"causes":["Phase 1 designs optimise for speed and identify the maximum tolerated dose rather than the optimal biological dose.","Dose-limiting toxicity is assessed in one cycle, missing cumulative and chronic toxicities.","Sponsors have no commercial incentive to study lower doses or shorter durations after approval.","Regulators historically accepted a single dose in registration trials.","Pharmacokinetic variability between patients is large but dosing is rarely individualised."],"currentEfforts":["FDA Project Optimus and the 2024 final guidance on dose optimisation require sponsors to compare multiple doses before registration.","PERSEPHONE, SOLD and Short-HER established that shorter adjuvant trastuzumab is non-inferior for many patients.","The CodeBreaK 100 randomised 960 mg vs 240 mg sotorasib comparison, required by the FDA, is the model for post-approval dose re-evaluation.","Dosimetry-personalised PRRT and radioligand therapy trials replace fixed activity with absorbed-dose-based dosing.","Intermittent and stop-and-restart dosing is being tested for nirogacestat in desmoid tumours and for venetoclax in AML.","Finaldose and academic pharmacometrics groups apply model-informed precision dosing to oncology drugs."],"successLooksLike":"Every new oncology drug is registered with a dose chosen by randomised comparison, the rate of dose reductions and discontinuations for toxicity on oral targeted agents falls below 20%, and duration of therapy is tested rather than assumed.","route":"/bottlenecks/b-dose-optimisation/"}
{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","aka":[],"tldr":"Cell therapies take weeks to make for one patient and cost hundreds of thousands of dollars. Isotopes run short.","summary":"Autologous CAR-T, TIL and TCR-T are one-batch-per-patient manufacturing: leukapheresis, shipping, transduction, expansion, release testing and return take several weeks, during which some patients progress or die, a proportion of products fail specification, and list prices run to several hundred thousand dollars before hospital costs. Only a small fraction of eligible patients receive approved CAR-T because of slot availability, referral and cost. Radioligand therapy has a different supply problem: lutetium-177 depends on a handful of reactors and enrichment sources, and actinium-225 for alpha therapy has been limited to a few curies a year worldwide from thorium-229 stocks, with accelerator and thorium-based production only now scaling. ADCs and bispecifics have complex biologics supply chains with a small number of contract manufacturers. In vivo CAR generation, allogeneic products, point-of-care and automated manufacturing, and new isotope production routes are the technical answers.","asOf":"2026-09-08","links":[{"label":"Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"},{"label":"Maude et al., Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia (ELIANA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1709866"},{"label":"US Department of Energy Isotope Program","url":"https://www.isotopes.gov/"}],"tags":[],"related":["radiopharma-roadmap","idea-reg-legacy-radium-recovery-ac225","idea-reg-ac225-accelerator-pharmacopoeia","idea-reg-yb176-enrichment-capacity","idea-reg-medical-isotope-reactor-reserve","idea-reg-alpha-emitter-portfolio","idea-reg-regional-radiopharmacy-hubs","idea-reg-isotope-supply-observatory","lu-177","ac-225"],"indications":["dlbcl","prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":["pluvicto","lutathera","ac225-psma"],"companies":["novartis","terrapower-isotopes","orano-med","itm","curium"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry","theranostics"],"trials":["vision"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"regulation-manufacturing","severity":"major","metrics":[{"label":"Estimated total cost of CAR-T therapy including list price and management of adverse events (2018 US analysis)","value":"Up to ~US$500,000 per patient","source":"Hernandez, Prasad & Gellad, JAMA Oncology 2018","url":"https://doi.org/10.1001/jamaoncol.2018.0977"},{"label":"Patients in ELIANA for whom tisagenlecleucel could not be manufactured","value":"7 of 92 enrolled","source":"Maude et al., NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1709866"},{"label":"Historic global actinium-225 supply from thorium-229 stockpiles","value":"~63 GBq (1.7 Ci) per year","source":"Robertson et al., Current Radiopharmaceuticals 2018","url":"https://doi.org/10.2174/1874471011666180416161908"}],"causes":["Autologous products are bespoke batches with no economies of scale.","Viral vector and GMP capacity are limited and expensive.","Actinium-225 has historically come only from decay of legacy thorium-229 held by a few government laboratories.","Lutetium-177 production depends on reactor time and enriched target material from few suppliers.","Release testing, cold-chain logistics and hospital accreditation add weeks and cost that no design optimisation removes."],"currentEfforts":["Umoja, Interius and Orna are developing in vivo CAR-T that programmes T cells inside the patient, removing manufacturing entirely.","Allogene, Caribou, Sana and Fate build off-the-shelf allogeneic CAR-T and CAR-NK products from healthy donor or iPSC sources.","Novartis' T-Charge and point-of-care manufacturing programmes at academic centres cut vein-to-vein time to days.","The US Department of Energy Isotope Program is producing accelerator-based actinium-225, and TerraPower Isotopes and Orano Med are scaling thorium-derived and accelerator-based supply.","ITM and Curium have expanded non-carrier-added lutetium-177 production, and Novartis has built dedicated radioligand plants.","Automated closed-system cell manufacturing platforms (for example, Miltenyi CliniMACS Prodigy and Lonza Cocoon) reduce labour and cleanroom needs."],"successLooksLike":"A CAR-T or equivalent cell therapy is available within a week of decision at a cost comparable to a course of biologic therapy, the majority of eligible patients actually receive it, and isotope supply is no longer the limiting factor for any approved radioligand.","route":"/bottlenecks/b-manufacturing-cell-therapy/"}
{"id":"paper-alsympca-radium-223-nejm-2013","kind":"paper","name":"ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases","aka":[],"tldr":"Radium-223, an injected alpha-emitting radioisotope that homes to bone, lengthened survival and delayed skeletal complications in men with castration-resistant prostate cancer that had spread to bone but not to organs.","summary":"Phase 3 placebo-controlled trial of 921 men with castration-resistant prostate cancer, symptomatic bone metastases and no visceral disease, randomised 2:1 to six injections of radium-223 or placebo with best standard of care.\n\nMedian overall survival was 14.9 versus 11.3 months (hazard ratio 0.70), time to first symptomatic skeletal event was delayed (15.6 versus 9.8 months) and myelosuppression was mild.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1213755"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23863050/"}],"tags":[],"related":["ra-223"],"indications":["prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca"],"people":["chris-parker"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1213755","pmid":"23863050","authors":"Parker C, Nilsson S, Heinrich D, et al.","paperType":"rct","findings":["Median overall survival 14.9 vs 11.3 months; hazard ratio 0.70.","Time to first symptomatic skeletal event 15.6 vs 9.8 months."],"whatItMeans":"Radium-223 is an option for symptomatic bone-predominant castration-resistant prostate cancer, now less used since lutetium-PSMA, and should not be combined with abiraterone after the ERA 223 fracture signal.","caveats":["No effect on PSA or soft tissue disease.","Combination with abiraterone increased fractures and deaths in ERA 223."],"changedPractice":true,"participants":921,"route":"/key-papers/paper-alsympca-radium-223-nejm-2013/"}
{"id":"paper-cabinet-cabozantinib-nejm-2024","kind":"paper","name":"CABINET (Alliance A021602): cabozantinib for advanced neuroendocrine tumours","aka":[],"tldr":"Cabozantinib delayed progression in previously treated advanced neuroendocrine tumours of both pancreatic and extra-pancreatic origin compared with placebo, adding a new option after somatostatin analogues, everolimus or radioligand therapy.","summary":"Two parallel phase 3 placebo-controlled trials of cabozantinib in 298 patients with progressive advanced neuroendocrine tumours: 203 with extra-pancreatic (including lung and small bowel) and 95 with pancreatic tumours, all previously treated.\n\nMedian progression-free survival was 8.4 versus 3.9 months in extra-pancreatic tumours (hazard ratio 0.38) and 13.8 versus 4.4 months in pancreatic tumours (hazard ratio 0.23); hypertension, fatigue and diarrhoea were common.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2403991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282913/"}],"tags":[],"related":[],"indications":["lung-net","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cabinet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2403991","pmid":"39282913","authors":"Chan JA, Geyer S, Zemla T, et al.","paperType":"rct","findings":["Extra-pancreatic: median progression-free survival 8.4 vs 3.9 months; hazard ratio 0.38.","Pancreatic: 13.8 vs 4.4 months; hazard ratio 0.23."],"whatItMeans":"Cabozantinib is approved for previously treated neuroendocrine tumours of any origin and is a standard later-line choice, including for lung carcinoids.","caveats":["Trials stopped early at interim analysis; overall survival not powered.","Dose reductions needed in most patients."],"changedPractice":true,"participants":298,"route":"/key-papers/paper-cabinet-cabozantinib-nejm-2024/"}
{"id":"paper-clarinet-lanreotide-nejm-2014","kind":"paper","name":"CLARINET: lanreotide in metastatic enteropancreatic neuroendocrine tumours","aka":[],"tldr":"The long-acting somatostatin analogue lanreotide roughly halved the risk of progression in non-functioning gut and pancreatic neuroendocrine tumours, extending the use of these drugs from symptom control to slowing tumour growth.","summary":"Phase 3 placebo-controlled trial of 204 patients with advanced, well- or moderately differentiated, non-functioning, somatostatin receptor-positive enteropancreatic neuroendocrine tumours (Ki-67 under 10 percent) randomised to lanreotide autogel 120 mg monthly or placebo.\n\nMedian progression-free survival was not reached with lanreotide against 18.0 months with placebo (hazard ratio 0.47), with benefit in pancreatic and midgut tumours and in patients with high hepatic tumour load.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1316158"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25014687/"}],"tags":[],"related":[],"indications":["pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1316158","pmid":"25014687","authors":"Caplin ME, Pavel M, Ćwikła JB, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.47.","24-month progression-free survival 65.1 percent vs 33.0 percent."],"whatItMeans":"Somatostatin analogues are the standard first-line antiproliferative treatment for grade 1 to 2 gastroenteropancreatic neuroendocrine tumours whether or not they cause a hormone syndrome.","caveats":["Most patients had stable disease at entry, so the natural history was slow.","No overall survival benefit shown."],"changedPractice":true,"participants":204,"route":"/key-papers/paper-clarinet-lanreotide-nejm-2014/"}
{"id":"paper-detect-a-science-2020","kind":"paper","name":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms","aka":[],"tldr":"The first prospective interventional study of a multi-analyte blood test (CancerSEEK) in asymptomatic people: 26 cancers were first detected by the blood test, most of them localised, and the test roughly doubled the number of cancers caught by standard screening.","summary":"DETECT-A enrolled 10,006 women aged 65-75 with no history of cancer in the Geisinger health system. A blood test measuring mutations in cell-free DNA and protein markers (CancerSEEK) was performed; a confirmed positive led to whole-body PET-CT, and imaging-positive participants were referred for diagnosis.\n\nTwenty-six cancers were detected by the blood test, of which 17 were localised or regional and 12 were treated with surgery with intent to cure. Standard-of-care screening detected a further 24 cancers, so combining the blood test with existing screening roughly doubled detection (from about a quarter to about half of incident cancers). Fewer than 1% of participants had an unnecessary invasive procedure.\n\nIt proved that a blood-first screening pathway can be safely operationalised and that many blood-detected cancers are at a curable stage.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.abb9601"},{"label":"ClinicalTrials.gov NCT03934866","url":"https://clinicaltrials.gov/study/NCT03934866"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2020,"doi":"10.1126/science.abb9601","pmid":"32345712","authors":"Lennon AM, Buchanan AH, Kinde I, et al.","paperType":"observational","findings":["Blood test alone detected 26 of 96 incident cancers (about 27% sensitivity); with standard screening the combined sensitivity was about 52%","17 of 26 blood-detected cancers were localised or regional; 12 patients had surgery with curative intent","The blood test found cancers in organs with no standard screening (ovary, kidney, appendix, uterus, lymphoma)","Participants did not reduce their uptake of standard screening after joining the study"],"whatItMeans":"A blood test can find early, treatable cancers in people who feel well, including cancers for which no screening exists. It is not a replacement for mammography or colonoscopy but a possible addition. Larger randomised trials are needed to show benefit outweighs harm.","caveats":["Single-arm, single health system, women only; no mortality endpoint","Sensitivity of about a quarter for all incident cancers means most cancers were missed","PET-CT confirmation for all positives is costly and exposes participants to radiation","CancerSEEK's commercial successor tests differ in design, so performance does not transfer directly"],"changedPractice":false,"participants":10006,"route":"/key-papers/paper-detect-a-science-2020/"}
{"id":"paper-netter-1-nejm-2017","kind":"paper","name":"NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide","aka":[],"tldr":"Radioligand therapy with lutetium-177 dotatate reduced the risk of progression or death by nearly 80 percent compared with high-dose octreotide in midgut neuroendocrine tumours, the first randomised proof that targeted radiation works in these cancers.","summary":"Phase 3 trial of 229 patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumours randomised to four cycles of 177Lu-Dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR 60 mg.\n\nProgression-free survival at 20 months was 65.2 versus 10.8 percent (hazard ratio 0.21), response 18 versus 3 percent, and an interim analysis suggested improved overall survival; myelosuppression was modest.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1607427"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28076709/"}],"tags":[],"related":["lu-177"],"indications":["small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1607427","pmid":"28076709","authors":"Strosberg J, El-Haddad G, Wolin E, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.21; 20-month rate 65.2 percent vs 10.8 percent.","Objective response 18 percent vs 3 percent."],"whatItMeans":"Lutetium-177 dotatate is a standard treatment for progressive small bowel neuroendocrine tumours after somatostatin analogues, and NETTER-2 has since moved it into first-line use for higher-grade tumours.","caveats":["Final overall survival difference (48.0 vs 36.3 months) did not reach significance, partly because of crossover.","Rare late myelodysplasia and leukaemia."],"changedPractice":true,"participants":229,"route":"/key-papers/paper-netter-1-nejm-2017/"}
{"id":"paper-netter-2-lancet-2024","kind":"paper","name":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","aka":[],"tldr":"Using the radioactive drug lutetium dotatate as the first treatment for faster-growing neuroendocrine tumours, rather than saving it for later, nearly tripled the time without progression compared with high-dose octreotide.","summary":"Open-label phase 3 trial of 226 patients with newly diagnosed, somatostatin-receptor-positive grade 2-3 (Ki-67 10-55%) advanced gastroenteropancreatic neuroendocrine tumours randomised 2:1 to four cycles of 177Lu-dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR (60 mg). Primary endpoint was PFS by blinded review.\n\nMedian PFS was 22.8 vs 8.5 months (HR 0.28) with an objective response rate of 43% vs 9%. Following NETTER-1 (which established lutetium dotatate in progressive midgut tumours), it moved radioligand therapy to the first line for higher-grade disease, where somatostatin analogues alone are weak.","asOf":"2026-09-08","links":[{"label":"PubMed search: NETTER-2 Lancet 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"},{"label":"ClinicalTrials.gov NCT03972488","url":"https://clinicaltrials.gov/study/NCT03972488"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00701-3","pmid":"38851203","authors":"Singh S, Halperin D, Myrehaug S, et al.","paperType":"rct","findings":["Median PFS 22.8 vs 8.5 months; HR 0.28 (95% CI 0.18-0.42).","Objective response 43.0% vs 9.3%.","Benefit consistent in grade 2 and grade 3 tumours and in pancreatic and small-bowel primaries.","Grade 3 or higher adverse events about 35% vs 28%; no cases of treatment-related myelodysplasia or leukaemia at the primary analysis.","Overall survival data immature; crossover to lutetium dotatate was permitted at progression."],"whatItMeans":"Patients newly diagnosed with an advanced grade 2 or 3 neuroendocrine tumour of the gut or pancreas that shows somatostatin receptors on imaging can now receive lutetium dotatate as their first treatment, gaining more than a year of additional disease control and a much higher chance of tumour shrinkage. It does not settle whether radioligand therapy is better than other first-line options such as capecitabine-temozolomide or everolimus, and long-term marrow safety with earlier use needs surveillance.","caveats":["Comparator was high-dose octreotide, which has limited anti-proliferative activity in grade 2-3 tumours.","Overall survival not yet shown; crossover will make it hard to demonstrate.","Long-term risks of earlier radioligand exposure (marrow, kidney, secondary leukaemia) require follow-up.","Requires somatostatin-receptor PET and nuclear medicine capacity; grade 3 tumours with Ki-67 above 55% were excluded."],"changedPractice":true,"participants":226,"route":"/key-papers/paper-netter-2-lancet-2024/"}
{"id":"paper-propsma-hofman-lancet-2020","kind":"paper","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","aka":[],"tldr":"PSMA PET-CT was 27 percentage points more accurate than CT and bone scan for finding spread in men with high-risk prostate cancer before treatment, with less radiation and more influence on management, and it has replaced conventional imaging where available.","summary":"Randomised multicentre trial of 302 men with high-risk localised prostate cancer randomised to conventional imaging (CT and bone scan) or gallium-68 PSMA PET-CT for staging, with crossover imaging to define a reference standard.\n\nAccuracy was 92 percent for PSMA PET-CT against 65 percent for conventional imaging, with higher sensitivity (85 versus 38 percent) and specificity, fewer equivocal results, lower radiation dose and more frequent management change.","asOf":"2026-09-17","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(20)30314-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32209449/"}],"tags":[],"related":["ga-68"],"indications":["prostate-bcr","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["propsma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7","pmid":"32209449","authors":"Hofman MS, Lawrentschuk N, Francis RJ, et al.","paperType":"rct","findings":["Accuracy 92 percent vs 65 percent (27 percent absolute difference).","Sensitivity 85 percent vs 38 percent; specificity 98 percent vs 91 percent."],"whatItMeans":"PSMA PET-CT is the preferred staging investigation for high-risk prostate cancer and for biochemical recurrence, though most treatment trials were designed with conventional imaging.","caveats":["Reference standard relied partly on imaging follow-up rather than histology.","Detecting more disease does not by itself prove better outcomes."],"changedPractice":true,"participants":302,"route":"/key-papers/paper-propsma-hofman-lancet-2020/"}
{"id":"paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","kind":"paper","name":"Efficacy and safety of high-specific-activity 131I-MIBG therapy in advanced pheochromocytoma or paraganglioma","aka":[],"tldr":"A purified radioactive form of MIBG, taken up by adrenaline-producing tumour cells, let a quarter of patients halve their blood pressure medication for at least six months and shrank tumours in about one in five, leading to the first approved radiopharmaceutical for these tumours.","summary":"Open-label single-arm multicentre phase 2 study of high-specific-activity iobenguane I-131 in patients with MIBG-avid unresectable or metastatic pheochromocytoma or paraganglioma, given as up to two therapeutic doses; 68 patients received at least one dose.\n\nAbout a quarter of patients achieved the primary endpoint of at least a 50 percent reduction in antihypertensive medication for six months or more, objective responses occurred in about 22 percent, and most patients had disease control; myelosuppression was the main toxicity. The FDA approved the product (Azedra) in 2018.","asOf":"2026-09-18","links":[{"label":"J Nucl Med 2019","url":"https://doi.org/10.2967/jnumed.118.217463"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30291194/"}],"tags":[],"related":["i-131"],"indications":["metastatic-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.118.217463","pmid":"30291194","authors":"Pryma DA, Chin BB, Noto RB, et al.","paperType":"observational","findings":["At least a 50 percent reduction in antihypertensive medication for six months or longer in about a quarter of patients.","Objective tumour response in about 22 percent; myelosuppression was the main adverse effect."],"whatItMeans":"Radionuclide therapy is a standard option for MIBG-avid metastatic pheochromocytoma and paraganglioma; somatostatin receptor targeted lutetium therapy is the alternative for SSTR-avid disease.","caveats":["Single-arm study with a blood pressure medication endpoint rather than survival.","The commercial product was later withdrawn from the US market for business reasons, limiting access."],"changedPractice":true,"participants":68,"route":"/key-papers/paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019/"}
{"id":"paper-rathl-interim-pet-adapted-abvd-advanced-hodgkin-nejm-2016","kind":"paper","name":"RATHL: adapted treatment guided by interim PET-CT in advanced Hodgkin lymphoma","aka":[],"tldr":"Using a PET scan after two cycles to decide the rest of treatment let patients with a clear scan drop bleomycin, sparing their lungs without losing cure, while those with a positive scan were escalated to stronger chemotherapy.","summary":"International randomised trial of 1,214 patients with advanced Hodgkin lymphoma who had an interim PET-CT after two cycles of ABVD; PET-negative patients were randomised to continue ABVD or switch to AVD (omitting bleomycin), and PET-positive patients were escalated to BEACOPP.\n\nThree-year progression-free survival was 85.7 percent with ABVD and 84.4 percent with AVD, with fewer pulmonary adverse events after bleomycin was dropped; PET-positive patients escalated to BEACOPP had a three-year progression-free survival of 67.5 percent, better than expected. PET-adapted therapy became standard.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1510093"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27332902/"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rathl"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1510093","pmid":"27332902","authors":"Johnson P, Federico M, Kirkwood A, et al.","paperType":"rct","findings":["Three-year progression-free survival 85.7 percent with continued ABVD versus 84.4 percent with AVD after a negative interim PET.","Fewer pulmonary and other toxic effects without bleomycin; PET-positive patients escalated to BEACOPP had 67.5 percent three-year progression-free survival."],"whatItMeans":"An interim PET scan after two cycles guides treatment of advanced Hodgkin lymphoma: drop bleomycin if negative, intensify if positive.","caveats":["The non-inferiority margin for AVD was not formally met in the intention-to-treat analysis, though the difference was small.","Predates brentuximab vedotin and nivolumab combinations, which now often replace ABVD."],"changedPractice":true,"participants":1214,"route":"/key-papers/paper-rathl-interim-pet-adapted-abvd-advanced-hodgkin-nejm-2016/"}
{"id":"paper-sempet-de-santis-jco-2004","kind":"paper","name":"SEMPET: FDG-PET as a predictor of viable tumour in post-chemotherapy seminoma residuals","aka":[],"tldr":"A PET scan reliably told apart residual masses that still contained living seminoma from scar tissue after chemotherapy, allowing surgeons to leave PET-negative masses alone rather than operating on all masses over 3 cm.","summary":"Prospective multicentre study of 51 patients with metastatic seminoma and residual masses after chemotherapy who underwent FDG-PET, with results validated against histology or clinical follow-up.\n\nPET had a sensitivity of 80 percent and specificity of 100 percent for viable tumour, and for residual lesions over 3 cm specificity and sensitivity were both 100 percent, outperforming CT size criteria.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2004","url":"https://doi.org/10.1200/JCO.2004.07.188"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15020605/"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2004,"doi":"10.1200/JCO.2004.07.188","pmid":"15020605","authors":"De Santis M, Becherer A, Bokemeyer C, et al.","paperType":"observational","findings":["Specificity 100 percent, sensitivity 80 percent for viable residual seminoma.","Sensitivity and specificity 100 percent for lesions over 3 cm."],"whatItMeans":"FDG-PET is standard for residual seminoma masses larger than 3 cm after chemotherapy, sparing most men surgery.","caveats":["Small study; false positives occur when PET is done too soon after chemotherapy, so scans are delayed at least six weeks."],"changedPractice":true,"participants":51,"route":"/key-papers/paper-sempet-de-santis-jco-2004/"}
{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","aka":[],"tldr":"A radioactive drug that homes to the PSMA protein on prostate cancer cells helped men with heavily pretreated metastatic prostate cancer live about four months longer, launching radioligand therapy as a mainstream treatment.","summary":"Open-label phase 3 trial of 831 men with PSMA-PET-positive metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor pathway inhibitor and one or two taxanes, randomised 2:1 to 177Lu-PSMA-617 (7.4 GBq every six weeks for up to six cycles) plus protocol-permitted standard care, or standard care alone. Primary endpoints were radiographic PFS and OS.\n\nMedian OS was 15.3 vs 11.3 months (HR 0.62) and median rPFS 8.7 vs 3.4 months (HR 0.40). It led to FDA and EMA approval of Pluvicto in 2022, the first radioligand therapy to show a survival benefit in a common cancer, and made PSMA PET a theranostic gatekeeper.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03511664","url":"https://clinicaltrials.gov/study/NCT03511664"}],"tags":[],"related":["psma-pet-to-rlt","lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet","pet-ct"],"targets":["psma"],"drugs":["pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","alpha-vs-beta","dosimetry"],"trials":["vision","psmafore"],"people":["karim-fizazi","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2107322","authors":"Sartor O, de Bono J, Chi KN, et al.","paperType":"rct","findings":["Median overall survival 15.3 vs 11.3 months; HR 0.62 (95% CI 0.52-0.74).","Median radiographic PFS 8.7 vs 3.4 months; HR 0.40 (99.2% CI 0.29-0.57).","PSA decline of 50% or more in 46% vs 7%; objective response in measurable disease 30% vs 2%.","Grade 3 or higher adverse events 53% vs 38%, mainly anaemia, thrombocytopenia and fatigue; dry mouth was common but rarely severe.","About 13% of screened patients were excluded by PSMA PET (PSMA-negative lesions), and early dropout in the control arm required protocol changes."],"whatItMeans":"Men with metastatic castration-resistant prostate cancer that has progressed after hormonal therapy and chemotherapy, and whose tumours show PSMA on a PET scan, can now receive lutetium-PSMA, which extends life, controls pain and is usually better tolerated than further chemotherapy. It has established a new treatment class in which a scan decides who gets the matching radioactive drug, and it is now being tested earlier in the disease (PSMAfore, PSMAddition).","caveats":["Standard care in the control arm excluded chemotherapy, radium-223 and other active drugs, and about 56% of control patients withdrew early, weakening the comparison.","Open-label; the OS benefit is nonetheless robust to sensitivity analyses.","Requires nuclear medicine infrastructure, isotope supply and PSMA PET access, which are unequally distributed.","PSMAfore in the pre-chemotherapy setting improved rPFS but not OS, because most control patients crossed over."],"changedPractice":true,"participants":831,"route":"/key-papers/paper-vision-nejm-2021/"}
{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","aka":["Ann Oncol","src-annals-oncology"],"tldr":"Annals of Oncology is ESMO's flagship journal, publishing European phase 3 trials, the ESMO Clinical Practice Guidelines and the abstract books for the ESMO Congress.","summary":"Annals of Oncology appears monthly and publishes the ESMO Clinical Practice Guidelines (free to read), ESMO-MCBS benefit scores, trial results often presented at ESMO Congress, translational biomarker studies and the ESMO congress abstract supplements. Published by Elsevier since 2019 (previously Oxford University Press). Hybrid access.","asOf":"2026-09-09","links":[{"label":"ESMO Guidelines","url":"https://www.esmo.org/guidelines"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: ESMO journal: trials, ESMO guidelines, ESMO-MCBS scorecards and congress abstracts. Access: Paywalled; guidelines and abstracts free."],"publisher":"Elsevier","url":"https://www.annalsofoncology.org","issn":"0923-7534","scope":"clinical oncology","access":"hybrid","founded":1990,"impactFactor":{"value":56.7,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["Annals of Oncology","Ann Oncol"],"society":"European Society for Medical Oncology","route":"/journals/annals-of-oncology/"}
{"id":"cancer-biotherapy-and-radiopharmaceuticals","kind":"journal","name":"Cancer biotherapy & radiopharmaceuticals","aka":["Cancer Biotherapy & Radiopharmaceuticals","Cancer Biotherapy and Radiopharmaceuticals","Cancer Biother Radiopharm"],"tldr":"Cancer Biotherapy and Radiopharmaceuticals covers immunotherapy, targeted biological agents and radiolabelled drugs for cancer imaging and treatment, read by nuclear medicine and biotherapy researchers.","summary":"Cancer Biotherapy & Radiopharmaceuticals has been published since 1996 and, according to the NLM catalogue, is issued from 2026 by SAGE Publications in Thousand Oaks, California, following its long run with Mary Ann Liebert; Crossref lists SAGE Publications as the publisher. As its title indicates, its two subjects are cancer biotherapy, meaning biological agents used to treat cancer, and radiopharmaceuticals, meaning radiolabelled compounds used to image and treat it. The NLM record lists it as a United States serial that is indexed in MEDLINE; it is not listed in DOAJ.","asOf":"2026-09-10","links":[{"label":"Homepage","url":"https://journals.sagepub.com/home/cbr"},{"label":"NLM Catalog","url":"https://www.ncbi.nlm.nih.gov/nlmcatalog/9605408"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"SAGE Publications (formerly Mary Ann Liebert)","url":"https://journals.sagepub.com/home/cbr","issn":"1084-9785","scope":"cancer biotherapy and radiopharmaceuticals","founded":1996,"matchNames":["Cancer Biother Radiopharm","Cancer biotherapy & radiopharmaceuticals","Cancer Biotherapy & Radiopharmaceuticals","Cancer Biotherapy and Radiopharmaceuticals"],"route":"/journals/cancer-biotherapy-and-radiopharmaceuticals/"}
{"id":"cancer-imaging","kind":"journal","name":"Cancer imaging","aka":["Cancer imaging : the official publication of the International Cancer Imaging Society","Cancer Imaging"],"tldr":"Cancer Imaging is the open-access journal of the International Cancer Imaging Society, covering CT, MRI, PET and other imaging of cancer. Read by radiologists and nuclear medicine specialists working in oncology.","summary":"Cancer Imaging is the official publication of the International Cancer Imaging Society (ICIS), published by BMC, part of Springer Nature. It is an open access, peer-reviewed journal publishing original articles, reviews and editorials by radiologists specialising in oncology, covering CT, MR, PET, ultrasound, radionuclide and multimodal imaging across tumour sites, including breast, chest, gastrointestinal, hepatobiliary and pancreatic, neuro-oncology, paediatric oncology and theranostics. DOAJ records CC BY and CC0 licences, an article processing charge with waivers, and that authors retain copyright. The journal began in 2000 (originally published by e-med), with the first issue of each early volume carrying the annual ICIS conference; it has been fully open access with BMC since 2014. Indexed in MEDLINE and deposited in PubMed Central.","asOf":"2026-09-10","links":[{"label":"Homepage","url":"https://cancerimagingjournal.biomedcentral.com/"},{"label":"NLM Catalog","url":"https://www.ncbi.nlm.nih.gov/nlmcatalog/101172931"},{"label":"DOAJ record","url":"https://doaj.org/toc/1470-7330"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"BMC (Springer Nature)","url":"https://cancerimagingjournal.biomedcentral.com/","issn":"1470-7330","scope":"cancer imaging","access":"open-access","founded":2000,"matchNames":["Cancer Imaging","Cancer imaging"],"society":"International Cancer Imaging Society","route":"/journals/cancer-imaging/"}
{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","aka":["Clin Cancer Res","CCR","src-clinical-cancer-research"],"tldr":"AACR's clinical journal: phase 1 dose-escalation trials, biomarker studies, pharmacodynamics and the FDA approval summaries written by agency reviewers.","summary":"Clinical Cancer Research appears twice a month and is the main venue for phase 1 trials of new oncology drugs, translational biomarker and pharmacokinetic analyses, and the FDA Oncology Center of Excellence approval summaries that explain the evidence behind each new indication. Hybrid access; free after 12 months.","asOf":"2026-09-09","links":[{"label":"AACR Journals","url":"https://aacrjournals.org"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: Phase 1 and 2 trials, biomarker studies and CCR Translations commentaries. Access: Paywalled."],"publisher":"American Association for Cancer Research","url":"https://aacrjournals.org/clincancerres","issn":"1078-0432","scope":"clinical oncology","access":"hybrid","founded":1995,"impactFactor":{"value":10,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["Clinical Cancer Research","Clin Cancer Res","CCR"],"society":"American Association for Cancer Research","route":"/journals/clinical-cancer-research/"}
{"id":"european-urology","kind":"journal","name":"European Urology","aka":["Eur Urol"],"tldr":"European Urology is the European Association of Urology's journal and the most cited urology title, publishing prostate, bladder and kidney cancer trials, the EAU guidelines and PSMA imaging studies.","summary":"Publishes the EAU guidelines, prostate-cancer screening and active-surveillance cohorts, PSMA PET and radioligand studies, and secondary analyses of the large phase 3 trials in bladder and kidney cancer. Hybrid access via Elsevier; sister titles include European Urology Oncology and European Urology Open Science.","asOf":"2026-09-09","links":[{"label":"EAU Guidelines","url":"https://uroweb.org/guidelines"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Elsevier","url":"https://www.europeanurology.com","issn":"0302-2838","scope":"urology","access":"hybrid","founded":1975,"impactFactor":{"value":25.2,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["European Urology","Eur Urol"],"society":"European Association of Urology","route":"/journals/european-urology/"}
{"id":"jama","kind":"journal","name":"JAMA","aka":["Journal of the American Medical Association","JAMA"],"tldr":"JAMA is the American Medical Association's flagship journal. It is strong on cancer screening, prevention, health-services and patient-reported-outcome research, and on the USPSTF recommendations.","summary":"JAMA is a weekly general-medicine journal. In oncology it carries screening and prevention trials, the US Preventive Services Task Force recommendation statements, health-policy and drug-pricing analyses, and landmark care-delivery studies such as Basch's 2017 electronic symptom-monitoring survival result. Hybrid access; research articles are free to read after 12 months.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/JAMA","links":[{"label":"JAMA Network oncology","url":"https://jamanetwork.com/collections/5644/oncology"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"American Medical Association (JAMA Network)","url":"https://jamanetwork.com/journals/jama","issn":"0098-7484","scope":"general medicine","access":"hybrid","founded":1883,"impactFactor":{"value":63.1,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["JAMA","Journal of the American Medical Association"],"society":"American Medical Association","route":"/journals/jama/"}
{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","aka":["JCO","J Clin Oncol","src-jco"],"tldr":"The Journal of Clinical Oncology is ASCO's flagship journal and the workhorse of clinical oncology, publishing trials, ASCO guidelines, and the abstract supplements for the ASCO Annual Meeting.","summary":"JCO publishes three issues a month, carrying phase 2 and 3 trials across all tumour types, ASCO clinical practice guidelines (for example on immune-related adverse events), health-services and survivorship research, and the annual-meeting abstract supplements that make it the most cited oncology journal by volume. Hybrid access; guidelines are free. Sister titles include JCO Precision Oncology, JCO Oncology Practice and JCO Global Oncology.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Journal_of_Clinical_Oncology","links":[{"label":"ASCO guidelines","url":"https://www.asco.org/practice-patients/guidelines"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: ASCO flagship journal: trials, guidelines (including living guidelines) and long-term follow-up of cooperative-group studies. Access: Paywalled; guidelines and many trials free."],"publisher":"American Society of Clinical Oncology","url":"https://ascopubs.org/journal/jco","issn":"0732-183X","scope":"clinical oncology","access":"hybrid","founded":1983,"impactFactor":{"value":42.1,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["Journal of Clinical Oncology","JCO","J Clin Oncol","Journal of Clinical Oncology (ASCO Annual Meeting abstract)"],"society":"American Society of Clinical Oncology","route":"/journals/jco/"}
{"id":"journal-of-medical-imaging-and-radiation-oncology","kind":"journal","name":"Journal of medical imaging and radiation oncology","aka":["J Med Imaging Radiat Oncol","JMIRO"],"tldr":"The journal of the Australian and New Zealand college for radiologists and radiation oncologists, covering diagnostic imaging, nuclear medicine and radiotherapy. Read by radiologists and radiation oncologists in Australasia and beyond.","summary":"The Journal of Medical Imaging and Radiation Oncology, also known as JMIRO, is recorded by NLM as the official journal of the Royal Australian and New Zealand College of Radiologists. It is published by Wiley (NLM lists Wiley-Blackwell Publishing Asia) and catalogued from 2008 as an Australian bimonthly, indexed for MEDLINE under Diagnostic Imaging, Neoplasms, Nuclear Medicine and Radiation Oncology. Crossref confirms Wiley as the publisher.","asOf":"2026-09-10","links":[{"label":"Homepage","url":"https://onlinelibrary.wiley.com/journal/17549485"},{"label":"NLM Catalog","url":"https://www.ncbi.nlm.nih.gov/nlmcatalog/101469340"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Wiley","url":"https://onlinelibrary.wiley.com/journal/17549485","issn":"1754-9477","scope":"radiology and radiation oncology","founded":2008,"matchNames":["J Med Imaging Radiat Oncol","Journal of medical imaging and radiation oncology","Journal of Medical Imaging and Radiation Oncology","JMIRO"],"society":"Royal Australian and New Zealand College of Radiologists","route":"/journals/journal-of-medical-imaging-and-radiation-oncology/"}
{"id":"journal-of-nuclear-medicine","kind":"journal","name":"Journal of Nuclear Medicine","aka":["JNM","J Nucl Med"],"tldr":"The Journal of Nuclear Medicine is the SNMMI's journal and the core venue for PET tracers and radioligand therapy: PSMA and somatostatin imaging, lutetium and actinium dosimetry, and theranostics trials.","summary":"The Journal of Nuclear Medicine appears monthly and publishes first-in-human tracer studies, PSMA PET diagnostic accuracy trials, radioligand-therapy dosimetry and outcomes (lutetium-177 PSMA and DOTATATE, actinium-225), and SNMMI procedure standards. Articles become free to read after a delay; the SNMMI annual meeting abstracts are published as a supplement.","asOf":"2026-09-09","links":[{"label":"SNMMI","url":"https://www.snmmi.org"}],"tags":[],"related":["src-snmmi","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Society of Nuclear Medicine and Molecular Imaging","url":"https://jnm.snmjournals.org","issn":"0161-5505","scope":"nuclear medicine","access":"hybrid","founded":1960,"matchNames":["Journal of Nuclear Medicine","JNM","J Nucl Med","The Journal of Nuclear Medicine"],"society":"Society of Nuclear Medicine and Molecular Imaging","route":"/journals/journal-of-nuclear-medicine/"}
{"id":"lancet","kind":"journal","name":"The Lancet","aka":["Lancet"],"tldr":"The Lancet is Britain's leading general medical journal and the other main home of practice-changing cancer trials, with a stronger global-health and policy voice than NEJM.","summary":"The Lancet appears weekly and publishes practice-changing oncology phase 3 trials (CheckMate 649, KEYNOTE-048, CARTITUDE-1, TRANSFORM), the Global Burden of Disease series, and Lancet Commissions that shape cancer policy. Elsevier hybrid model: subscription with an open-access option; abstracts free. Known for editorial campaigning on health inequality and for the HPV-vaccination and cancer-survival population studies that appear in this corpus.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/The_Lancet","links":[{"label":"Oncology collection","url":"https://www.thelancet.com/clinical/diseases/cancer"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Elsevier","url":"https://www.thelancet.com/journals/lancet/home","issn":"0140-6736","scope":"general medicine","access":"hybrid","founded":1823,"impactFactor":{"value":98.4,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["The Lancet","Lancet"],"route":"/journals/lancet/"}
{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","aka":["Lancet Oncol","src-lancet-oncology"],"tldr":"The Lancet Oncology is the leading specialist cancer journal for clinical trials. It publishes phase 2 and 3 trials, long-term follow-up, quality-of-life analyses and global-oncology policy Commissions.","summary":"The Lancet Oncology appears monthly plus online-first and publishes a large share of randomised oncology trials that do not go to NEJM, with particular strength in radiotherapy, surgery, supportive care and health-system studies (IBIS-I tamoxifen prevention, MASAI AI mammography, GAP70 geriatric assessment in this corpus). Its Commissions and Series drive policy debates on drug pricing, radiotherapy access and cancer in low-income countries. Elsevier hybrid model; abstracts free.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/The_Lancet_Oncology","links":[{"label":"Lancet Oncology Commissions","url":"https://www.thelancet.com/journals/lanonc/commissions"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: Phase 2 and 3 trials, meta-analyses, global oncology policy and the ESMO-aligned commentaries. Access: Paywalled; abstracts free."],"publisher":"Elsevier","url":"https://www.thelancet.com/journals/lanonc/home","issn":"1470-2045","scope":"clinical oncology","access":"hybrid","founded":2000,"impactFactor":{"value":41.6,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["Lancet Oncology","The Lancet Oncology","Lancet Oncol"],"route":"/journals/lancet-oncology/"}
{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","aka":["Nat Med","src-nature-medicine"],"tldr":"Nature Medicine is Nature's clinical journal and now a top venue for early-phase and biomarker-rich cancer trials, medical AI studies and cell-therapy reports.","summary":"Nature Medicine appears monthly and publishes phase 1 and 2 trials with deep translational analysis (MagnetisMM-3 elranatamab in this corpus), circulating tumour DNA and multi-cancer early-detection studies, large medical-AI validations and consensus reporting guidelines for AI in medicine. Hybrid access with a Springer Nature open-access option.","asOf":"2026-09-09","links":[{"label":"Nature Medicine cancer","url":"https://www.nature.com/nm/research-articles?subject=cancer"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: Translational medicine including cancer vaccines, AI diagnostics and phase 1 to 3 trials with mechanistic depth. Access: Paywalled; abstracts free; some open access."],"publisher":"Springer Nature","url":"https://www.nature.com/nm/","issn":"1078-8956","scope":"translational medicine","access":"hybrid","founded":1995,"impactFactor":{"value":58.7,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["Nature Medicine","Nat Med"],"route":"/journals/nature-medicine/"}
{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","aka":["NEJM","N Engl J Med","src-nejm"],"tldr":"NEJM is the most influential medical journal. When a cancer drug trial changes how patients are treated, the paper is usually here, often published the same day it is presented at ASCO, ESMO or ASH.","summary":"Weekly general-medicine journal with the highest bar for randomised evidence and the largest share of practice-changing oncology phase 3 trials (IRIS imatinib, KEYNOTE-189, DESTINY-Breast04, CheckMate 067, ZUMA-1 and dozens more in this corpus). Editorials and correspondence often carry the critical reading of a trial. Paywalled, with abstracts free and many trial papers free six months after publication; requires a data-sharing statement for clinical trials under ICMJE rules.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/The_New_England_Journal_of_Medicine","links":[{"label":"Hematology/Oncology specialty page","url":"https://www.nejm.org/browse/specialty/hematology-oncology"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Holds: The practice-changing phase 3 trials, most published simultaneously with ASCO, ESMO and ASH presentations. Access: Paywalled; abstracts free; many trial papers free after 6 months."],"publisher":"NEJM Group / Massachusetts Medical Society","url":"https://www.nejm.org","issn":"0028-4793","scope":"general medicine","access":"subscription","founded":1812,"impactFactor":{"value":96.2,"year":2023,"source":"Clarivate Journal Citation Reports 2024 (2023 JIF)"},"matchNames":["NEJM","N Engl J Med","New England Journal of Medicine","The New England Journal of Medicine"],"society":"Massachusetts Medical Society","route":"/journals/nejm/"}
{"id":"radiology","kind":"journal","name":"Radiology","aka":["Radiology (RSNA)"],"tldr":"Radiology is the RSNA's flagship journal, publishing imaging research including cancer screening performance, AI image analysis and response assessment.","summary":"Radiology appears monthly. In oncology it publishes mammography and lung CT screening performance studies, AI reader studies, contrast and radiation-dose research and imaging-based response and prognosis work. Hybrid access via RSNA; sister titles include Radiology: Artificial Intelligence and Radiology: Imaging Cancer.","asOf":"2026-09-09","links":[{"label":"RSNA","url":"https://www.rsna.org"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Radiological Society of North America","url":"https://pubs.rsna.org/journal/radiology","issn":"0033-8419","scope":"radiology","access":"hybrid","founded":1923,"matchNames":["Radiology"],"society":"Radiological Society of North America","route":"/journals/radiology/"}
{"id":"science-translational-medicine","kind":"journal","name":"Science Translational Medicine","aka":["Sci Transl Med"],"tldr":"Science Translational Medicine is AAAS's translational journal, publishing the bench-to-bedside cancer papers on liquid biopsy, CAR-T engineering, tumour-immune biology and new imaging agents.","summary":"Science Translational Medicine (Sci Transl Med) is the translational journal of the American Association for the Advancement of Science (AAAS), founded in 2009, appearing weekly and available by subscription with delayed free access. It publishes bench-to-bedside studies with strong mechanistic grounding, including early circulating tumour DNA detection methods, CAR-T design and toxicity work, tumour-immune biology and PET tracer development. Its readers are translational researchers moving discoveries toward the clinic. Within Nuclide it is linked from the biographies of Lecia Sequist, Jeanne Tie, Michel Sadelain, Marcela Maus, Marie-Catherine Vozenin and Constance Lehman, and a reader would use it for the liquid biopsy, CAR-T and imaging papers that precede trials.","asOf":"2026-09-09","links":[{"label":"Science journals","url":"https://www.science.org"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"American Association for the Advancement of Science","url":"https://www.science.org/journal/stm","issn":"1946-6234","scope":"translational medicine","founded":2009,"matchNames":["Science Translational Medicine","Sci Transl Med"],"society":"American Association for the Advancement of Science","route":"/journals/science-translational-medicine/"}
{"id":"coronary-artery-disease","kind":"indication","name":"Coronary artery disease","aka":[],"tldr":"The arteries that feed the heart muscle narrow with fatty plaque, so parts of the heart can be starved of blood, especially during exercise or stress.","summary":"Coronary artery disease (CAD) is atherosclerotic narrowing of the epicardial coronary arteries, causing a mismatch between myocardial oxygen supply and demand that manifests as angina, ischaemia on stress testing, or myocardial infarction. Nuclear cardiology's role is functional: myocardial perfusion imaging (MPI) with SPECT or PET compares blood flow at rest and under stress (exercise or pharmacologic vasodilation) to localise and size reversible (ischaemic) versus fixed (infarcted or scarred) defects, and to risk-stratify patients for revascularisation versus medical therapy.\n\nSPECT MPI with technetium-99m sestamibi or tetrofosmin, or historically thallium-201, remains the most widely performed test worldwide. PET MPI with rubidium-82, nitrogen-13 ammonia, or since 2024 fluorine-18 flurpiridaz adds absolute myocardial blood flow quantification (mL/min/g) and lower radiation dose per study, at the cost of needing an on-site generator or cyclotron for the shorter-lived tracers. ASNC/SNMMI procedure standards and appropriate use criteria govern tracer choice, dosing and interpretation.\n\nOpen questions in practice include how routinely to add absolute flow quantification to standard visual and semi-quantitative reads, and how flurpiridaz's long half-life (which permits exercise stress PET, previously impractical with short-lived PET tracers) will change referral patterns away from SPECT.","asOf":"2026-09-22","links":[{"label":"ASNC/SNMMI imaging guideline: PET nuclear cardiology procedures","url":"https://www.asnc.org/wp-content/uploads/2024/06/s12350-016-0522-3.pdf"},{"label":"SNMMI/ACC/ASNC updated appropriate use criteria for PET myocardial perfusion imaging 2.0","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Appropriate%20Use%20Criteria/Updated%20AUC%20for%20PET%20Myocardial%20Perfusion%20Imaging-2.0%20FINAL.pdf"}],"tags":[],"related":["tc-99m-sestamibi","tc-99m-tetrofosmin","tl-201-chloride","rb-82-chloride","n-13-ammonia","f-18-flurpiridaz","f-18","tc-99m","n-13","rb-82","tl-201"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"cardiology","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"diagnosis of ischaemia","approach":"Stress/rest SPECT or PET myocardial perfusion imaging with exercise or pharmacologic (vasodilator or dobutamine) stress","refs":["tc-99m-sestamibi","tc-99m-tetrofosmin","tl-201-chloride","rb-82-chloride","n-13-ammonia","f-18-flurpiridaz"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"route":"/indications/coronary-artery-disease/"}
{"id":"cardiac-amyloidosis-attr","kind":"indication","name":"Cardiac amyloidosis (transthyretin, ATTR-CM)","aka":[],"tldr":"A misfolded blood protein called transthyretin builds up as stiff deposits inside the heart muscle, making it thicken and stop relaxing properly. A bone-scanning tracer that also sticks to these deposits can diagnose it without a heart biopsy.","summary":"Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by misfolded transthyretin (wild-type or a hereditary variant) depositing as amyloid fibrils in the myocardium, producing a restrictive, thick-walled heart failure phenotype that mimics hypertensive heart disease on echocardiography. It is distinct from AL (light-chain) cardiac amyloidosis, which needs haematology-led treatment, so excluding a plasma cell clone (serum/urine immunofixation and free light chains) alongside imaging is mandatory.\n\nBone-avid Tc-99m bisphosphonate tracers (pyrophosphate, or DPD/HMDP outside the US) bind ATTR amyloid deposits, apparently via calcium co-deposition, and are read against rib (bone) uptake on a 0-3 visual grade. Gillmore et al. (2016, JAMA Cardiology, n=1,217) showed grade 2-3 uptake, combined with the absence of a monoclonal protein, had 100% specificity and positive predictive value for ATTR-CM, avoiding endomyocardial biopsy in most patients. Multisociety expert consensus (ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI, with a 2021 addendum) now requires SPECT or SPECT/CT confirmation of myocardial uptake; planar grading or the heart-to-contralateral ratio alone is no longer sufficient for diagnosis.\n\nThe test matters clinically because ATTR-specific therapies (TTR stabilisers and gene-silencing agents) are now available, so a confident non-invasive diagnosis changes management; this is outside Nuclide's therapeutic scope but is the reason demand for pyrophosphate scanning has grown sharply since the mid-2010s.","asOf":"2026-09-22","links":[{"label":"Gillmore et al. 2016, JAMA Cardiology: Tc-99m PYP scintigraphy for ATTR cardiac amyloidosis","url":"https://jamanetwork.com/journals/jamacardiology/fullarticle/2546034"},{"label":"ASNC practice points: 99mTc-pyrophosphate imaging for cardiac amyloidosis","url":"https://www.asnc.org/wp-content/uploads/2024/05/ASNC-Practice-Point-99mTechnetium-Pyrophosphate.2016.pdf"}],"tags":[],"related":["tc-99m-pyrophosphate","tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"cardiology","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"non-invasive diagnosis of ATTR-CM","approach":"Tc-99m pyrophosphate (or DPD/HMDP) SPECT/CT grade 2-3 myocardial uptake plus exclusion of a monoclonal light-chain clone","refs":["tc-99m-pyrophosphate"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"route":"/indications/cardiac-amyloidosis-attr/"}
{"id":"cardiac-sarcoidosis","kind":"indication","name":"Cardiac sarcoidosis","aka":[],"tldr":"Sarcoidosis is patches of inflammation that can form in the heart as well as the lungs and other organs, and it can trigger dangerous heart rhythms or heart failure. A PET scan that shows heart inflammation, paired with a separate scan of blood flow, helps find and track it.","summary":"Cardiac sarcoidosis (CS) is myocardial granulomatous inflammation, part of the systemic disease sarcoidosis, that can cause heart block, ventricular arrhythmia, or heart failure, often before it is suspected clinically. Because endomyocardial biopsy has poor sensitivity (patchy involvement), imaging plays a central diagnostic and monitoring role.\n\nThe 2017 joint SNMMI-ASNC expert consensus document describes a two-part cardiac PET protocol: a resting myocardial perfusion scan (with N-13 ammonia or Rb-82, or a SPECT perfusion tracer where PET perfusion is unavailable) to map blood flow, followed by F-18 FDG PET after patient preparation (prolonged fasting and a high-fat, low-carbohydrate diet, sometimes with heparin) to suppress normal myocardial glucose use and reveal focal inflammatory FDG uptake. The perfusion and metabolism images are read together: a perfusion defect with matched reduced FDG uptake suggests scar, a defect with FDG uptake mismatch suggests active inflammation superimposed on damaged tissue, and normal perfusion with focal FDG uptake suggests early active disease without fixed damage.\n\nF-18 FDG itself is outside this cardiac-agents file (it is a general oncology and inflammation tracer elsewhere in the corpus); the tracers recorded here contribute the perfusion half of the CS protocol, which is required at baseline and at follow-up scans alongside the FDG study.","asOf":"2026-09-22","links":[{"label":"Joint SNMMI-ASNC expert consensus document on 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring (J Nucl Med 2017)","url":"https://jnm.snmjournals.org/content/58/8/1341"}],"tags":[],"related":["n-13-ammonia","rb-82-chloride","tc-99m-sestamibi","tc-99m-tetrofosmin","f-18","n-13","rb-82"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"cardiology","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"diagnostic PET protocol for suspected cardiac sarcoidosis","approach":"Resting perfusion PET (N-13 ammonia or Rb-82) or SPECT perfusion, paired with F-18 FDG PET after myocardial glucose suppression, read as a perfusion/metabolism pattern","refs":["n-13-ammonia","rb-82-chloride","tc-99m-sestamibi","tc-99m-tetrofosmin"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"route":"/indications/cardiac-sarcoidosis/"}
{"id":"tc-99m-sestamibi","kind":"drug","name":"Technetium Tc-99m sestamibi","aka":["Sestamibi","MIBI","Miraluma (breast imaging)"],"tldr":"A radioactive tracer injected into a vein that lodges inside heart muscle cells in proportion to blood flow, so a gamma camera picture taken after exercise or a stress drug shows which parts of the heart are not getting enough blood.","summary":"Technetium Tc-99m sestamibi (Cardiolite) is a cationic isonitrile SPECT perfusion agent, FDA-approved in December 1990, supplied as a cold kit reconstituted with generator-eluted Tc-99m and injected intravenously for rest and stress myocardial perfusion imaging. Its first-pass myocardial extraction fraction is 55-68%, lower than thallium-201's 82-88% but adequate because the higher injectable activity and 140 keV photon (near-ideal for gamma cameras) compensate with better image counts and a 6-hour half-life that allows same-day or two-day rest/stress protocols.\n\nThe FDA label indications are detecting coronary artery disease by localising reversible (ischaemic) and non-reversible (infarcted) defects, and evaluating myocardial function to inform patient management. The suggested adult dose range is 370-1,110 MBq (10-30 mCi) per injection; a separate approved indication (as Miraluma) at 740-1,110 MBq is for breast imaging as an adjunct to mammography, outside this cardiac scope.\n\nIn practice sestamibi SPECT (usually gated, giving ejection fraction and wall motion alongside perfusion) is the workhorse test to decide whether a patient with chest pain or an abnormal stress test needs coronary angiography and revascularisation versus medical therapy, and it can also serve as the resting perfusion half of a cardiac sarcoidosis PET/SPECT work-up when PET perfusion tracers are unavailable.","asOf":"2026-09-22","links":[{"label":"FDA label: Cardiolite (technetium Tc-99m sestamibi), revised December 2019","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019785s022lbl.pdf"},{"label":"First-pass myocardial extraction fractions of Tc-99m agents and Tl-201 (J Nucl Med Technol review)","url":"https://tech.snmjournals.org/content/jnmt/35/1/3.full.pdf"},{"label":"ASNC/SNMMI PET nuclear cardiology procedure standard (perfusion tracer comparison and cardiac sarcoidosis protocol)","url":"https://www.asnc.org/wp-content/uploads/2024/06/s12350-016-0522-3.pdf"}],"tags":["SPECT","myocardial perfusion","technetium"],"related":["tc-99m-tetrofosmin","tl-201-chloride","tc-99m","tl-201"],"indications":["coronary-artery-disease","cardiac-sarcoidosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Cardiolite","modality":"SPECT tracer","mechanism":"A lipophilic cationic isonitrile complex of Tc-99m that crosses cell membranes passively and accumulates in mitochondria, driven by the mitochondrial and plasma membrane potentials of viable myocytes. Myocardial uptake is proportional to coronary blood flow at the time of injection, with a first-pass extraction fraction of about 55-68% (roughly 65% at rest) that plateaus (\"rolls off\") at high flow rates, so it somewhat underestimates very high flow. Unlike thallium-201 it shows minimal redistribution, so a snapshot taken at stress genuinely reflects flow at the moment of injection, and separate rest and stress doses are needed.","approvals":[{"region":"US","year":1990,"indication":"Detecting coronary artery disease by localising myocardial ischaemia and infarction, and evaluating myocardial function"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"370-1,110 MBq (10-30 mCi) per dose for myocardial imaging (rest and stress doses given separately); imaging typically begins 15-60 minutes after injection","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019785s022lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-sestamibi/"}
{"id":"tc-99m-tetrofosmin","kind":"drug","name":"Technetium Tc-99m tetrofosmin","aka":["Tetrofosmin"],"tldr":"A radioactive tracer, chemically similar to Cardiolite, injected into a vein and taken up by heart muscle in proportion to blood flow; a gamma camera scan after rest and after exercise or a stress drug shows areas with reduced blood supply.","summary":"Technetium Tc-99m tetrofosmin (Myoview), initial US approval 1996, is a diphosphine SPECT perfusion agent supplied as a cold kit for reconstitution with Tc-99m generator eluate. It shares sestamibi's core pharmacokinetic profile: passive, blood-flow-proportional myocardial uptake with negligible redistribution, so separate rest and stress doses are required, and its 140 keV photon suits standard gamma cameras.\n\nThe FDA label covers two indications: myocardial perfusion imaging under rest and/or exercise or pharmacologic stress to delineate regions of reversible ischaemia or infarcted myocardium in patients with known or suspected coronary artery disease, and assessment of left ventricular function (ejection fraction and wall motion) via gated SPECT. The recommended dose range is 185-1,221 MBq (5-33 mCi); on a same-day protocol the first (rest or low-level stress) dose is 185-444 MBq followed 1-4 hours later by 555-1,221 MBq for the second acquisition.\n\nIts first-pass extraction fraction (about 54%) is modestly lower than sestamibi's, and comparative studies (e.g. dipyridamole-stress SPECT in mild-to-moderate CAD) have found sestamibi detects more reversible defects, attributed to tetrofosmin's earlier extraction \"roll-off\" at high flow; both remain widely used interchangeably in routine SPECT MPI.","asOf":"2026-09-22","links":[{"label":"FDA label: Myoview (technetium Tc-99m tetrofosmin), 2022 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020372Orig1s033lbl.pdf"},{"label":"First-pass extraction fractions of Tl-201, Tc-99m sestamibi and tetrofosmin (Circ Cardiovasc Imaging)","url":"https://www.ahajournals.org/doi/10.1161/circimaging.109.854893"},{"label":"Sestamibi vs tetrofosmin defect detection in mild-to-moderate CAD (JACC 2001)","url":"https://www.jacc.org/doi/10.1016/S0735-1097(00)01148-7"}],"tags":["SPECT","myocardial perfusion","technetium"],"related":["tc-99m-sestamibi","tl-201-chloride","tc-99m"],"indications":["coronary-artery-disease","cardiac-sarcoidosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Myoview","modality":"SPECT tracer","mechanism":"A lipophilic cationic diphosphine complex of Tc-99m, taken up by myocytes in proportion to blood flow and retained largely by binding within mitochondria, driven by the transmembrane and mitochondrial potentials, with minimal redistribution after uptake. Its first-pass myocardial extraction fraction is around 54%, similar to but slightly lower than sestamibi's, so its uptake-versus-flow curve plateaus (rolls off) at a somewhat lower flow rate, which can mean smaller apparent defect extent/severity than sestamibi in mild-to-moderate disease.","approvals":[{"region":"US","year":1996,"indication":"Myocardial perfusion imaging under rest and/or exercise or pharmacologic stress to delineate reversible ischaemia and infarcted myocardium"},{"region":"US","year":1999,"indication":"Assessment of left ventricular function (ejection fraction and wall motion)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"185-1,221 MBq (5-33 mCi) per dose; same-day protocol gives 185-444 MBq first then 555-1,221 MBq 1-4 hours later; imaging can begin 15 minutes after injection","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020372Orig1s033lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-tetrofosmin/"}
{"id":"tl-201-chloride","kind":"drug","name":"Thallous chloride Tl-201","aka":["Thallium-201","Tl-201 chloride"],"tldr":"The original heart-blood-flow tracer: a radioactive form of the metal thallium that heart muscle cells pull in almost like potassium, so a scan straight after exercise and a second scan hours later can tell a starved-but-alive muscle from permanently dead muscle without a second injection.","summary":"Thallous chloride Tl-201 is the oldest of the routine myocardial perfusion agents, taken up by the Na+/K+-ATPase pump with a first-pass extraction fraction of roughly 82-88%, the highest of the perfusion tracers and closest to a linear flow tracer. Its defining clinical property is redistribution: after stress injection, thallium washes out of normally perfused myocardium and re-enters previously ischaemic but viable segments over several hours, so a single injection with stress and delayed (redistribution) imaging can separate ischaemia from infarction/scar and assess viability, a capability the non-redistributing Tc-99m agents lack without a second dose.\n\nThe current FDA label indication is myocardial perfusion imaging (planar or SPECT) for diagnosis of coronary artery disease by localising non-reversible defects (infarction) and reversible defects (ischaemia, with exercise or pharmacologic stress), plus a separate indication for localising parathyroid hyperactivity pre- and post-operatively. Recommended adult doses are 37-74 MBq (1-2 mCi) for planar imaging and 74-111 MBq (2-3 mCi) for SPECT.\n\nBecause thallium's 80 keV and 167 keV photons are lower-energy than technetium's 140 keV, image quality and count statistics are inferior, and the longer 73-hour half-life gives a higher radiation dose per study; the Tc-99m agents and PET tracers have therefore displaced most of thallium's rest/stress workload, but it remains in use, particularly for viability assessment and as the low-dose rest half of dual-isotope protocols.","asOf":"2026-09-22","links":[{"label":"FDA label: Thallous Chloride Tl 201 Injection, 2025 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/018150s029lbl.pdf"},{"label":"First-pass extraction fraction comparison table (J Nucl Med Technol review)","url":"https://tech.snmjournals.org/content/jnmt/35/1/3.full.pdf"}],"tags":["SPECT","myocardial perfusion","viability"],"related":["tc-99m-sestamibi","tc-99m-tetrofosmin","tc-99m","tl-201"],"indications":["coronary-artery-disease"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"SPECT tracer","mechanism":"Tl+ is a potassium analogue actively taken up by viable myocytes via the Na+/K+-ATPase pump, giving the highest first-pass myocardial extraction fraction of the routine perfusion agents (about 82-88%) and a near-linear relationship with blood flow across a wide range. Unlike the Tc-99m agents, thallium redistributes over hours as it re-equilibrates between myocardial and blood compartments, which is exploited clinically: a stress image followed by 3-4 hour (or 24 hour) redistribution imaging distinguishes reversible ischaemia (fills in on redistribution) from fixed scar (stays a defect), and can assess myocardial viability without a second injection.","approvals":[{"region":"US","year":1977,"indication":"Myocardial perfusion imaging (planar or SPECT) for diagnosis of coronary artery disease by localisation of infarction and, with stress, ischaemia"},{"region":"US","year":1977,"indication":"Localisation of sites of parathyroid hyperactivity pre- and post-operatively"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"Planar myocardial imaging 37-74 MBq (1-2 mCi); SPECT myocardial imaging 74-111 MBq (2-3 mCi); parathyroid localisation 75-130 MBq (2-3.5 mCi)","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/018150s029lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tl-201-chloride/"}
{"id":"rb-82-chloride","kind":"drug","name":"Rubidium Rb-82 chloride","aka":["Rb-82","82Rb"],"tldr":"A generator-produced radioactive form of the metal rubidium, chemically similar to potassium, given as a fast intravenous infusion; because it decays away in about a minute and a half it can be produced on site without a cyclotron, letting a PET scan of heart blood flow be done in around half an hour.","summary":"Rubidium Rb-82 chloride, marketed via the CardioGen-82 strontium-82/rubidium-82 generator, is a PET myocardial perfusion agent behaving like a potassium analogue with a first-pass extraction fraction of about 65% (and flow-dependent roll-off similar to or greater than the Tc-99m SPECT agents). Its ultra-short 75-second half-life is both its main practical advantage, no cyclotron is required since the generator is eluted with saline immediately before each dose, and its main constraint: imaging must begin within 60-130 seconds of infusion and the generator itself is regulated for strontium breakthrough.\n\nThe FDA label indicates it for PET imaging of the myocardium under rest or pharmacologic stress to evaluate regional myocardial perfusion in adults with suspected or existing coronary artery disease. Recommended adult dosing (Model 510 infusion system) is 1,480 MBq (40 mCi) per rest or stress component, with a range of 1,110-2,220 MBq, infused intravenously at 50 mL/min; a newer Model 1700 system doses by body weight (10-30 MBq/kg).\n\nRb-82 PET's speed (a full rest/stress study in about 30 minutes) and generator-based, cyclotron-free production have made it the most widely used PET perfusion tracer in the US for routine CAD work-up, and it is also used, alongside or instead of N-13 ammonia, as the resting perfusion half of the cardiac sarcoidosis PET protocol.","asOf":"2026-09-22","links":[{"label":"FDA label: CardioGen-82 (rubidium Rb 82 generator), 2024 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/019414s034lbl.pdf"},{"label":"EMC SmPC: Cardiogen-82 (Rb-82 extraction fraction 65%)","url":"https://www.medicines.org.uk/emc/product/15771/smpc"},{"label":"ASNC/SNMMI PET nuclear cardiology procedure standard","url":"https://www.asnc.org/wp-content/uploads/2024/06/s12350-016-0522-3.pdf"}],"tags":["PET","myocardial perfusion","generator"],"related":["n-13-ammonia","f-18-flurpiridaz","tc-99m","n-13","rb-82"],"indications":["coronary-artery-disease","cardiac-sarcoidosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"CardioGen-82","modality":"PET tracer","mechanism":"Rb+ is a potassium analogue taken up by viable myocytes through the Na+/K+-ATPase pump, similarly to thallium, with a first-pass myocardial extraction fraction of about 65% at rest that falls further at high flow (roughly 40-70% across the physiological range, per comparative reviews), a bigger flow-dependent roll-off than the newer tracer flurpiridaz. Its 75-second physical half-life means it is produced on demand from a strontium-82/rubidium-82 generator immediately before each rest and stress dose, with no cyclotron needed on site, but also that imaging must start within roughly a minute of the infusion and the whole rest-stress study can be completed in about 30 minutes.","approvals":[{"region":"US","year":1989,"indication":"PET imaging of the myocardium under rest or pharmacologic stress to evaluate regional myocardial perfusion in adults with suspected or existing coronary artery disease"}],"mechanismSteps":[],"dosing":{"route":"Intravenous infusion (generator-eluted, produced immediately before use)","schedule":"1,480 MBq (40 mCi) per rest or stress component, range 1,110-2,220 MBq, infused at 50 mL/min (Model 510); 10-30 MBq/kg on Model 1700; imaging starts 60-90 seconds after infusion, rest and stress separated by a minimum 10 minutes","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/019414s034lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/rb-82-chloride/"}
{"id":"n-13-ammonia","kind":"drug","name":"Ammonia N-13","aka":["13N-ammonia","N-13 ammonia"],"tldr":"A radioactive form of ammonia gas, made fresh on site in a cyclotron and injected into a vein; heart muscle cells trap it in proportion to how much blood is flowing through, so a PET scan maps blood flow to the heart very precisely.","summary":"Ammonia N-13 injection is a cyclotron-produced PET myocardial perfusion agent, initial US approval 2007 (NDA 22-119, full approval 2011), taken up and metabolically trapped in myocytes as N-13 glutamine, giving image quality and quantitative accuracy that ASNC/SNMMI guidelines rate among the best of the FDA-approved and CMS-reimbursable PET perfusion tracers (the others being Rb-82; O-15 water is used in Europe but is not FDA approved).\n\nThe FDA label indicates it for diagnostic PET imaging of the myocardium under rest or pharmacologic stress to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease. The recommended adult dose is 10-20 mCi (0.368-0.736 GBq) as an intravenous bolus for each of the rest and stress studies, with the stress study begun 40 minutes or more after the first injection to allow adequate decay of the 9.97-minute isotope; imaging starts about 3 minutes after injection.\n\nBecause it requires an on-site or very nearby cyclotron (unlike generator-based Rb-82), N-13 ammonia's use is concentrated at academic and large hospital PET centres; it is the other guideline-endorsed option, alongside Rb-82, for the resting perfusion half of the two-part cardiac sarcoidosis PET protocol, and is favoured by some centres for absolute myocardial blood flow quantification given its longer half-life relative to Rb-82, which allows more complete kinetic sampling.","asOf":"2026-09-22","links":[{"label":"FDA label: Ammonia N 13 Injection, 2011 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022119s001lbl.pdf"},{"label":"FDA approval package, NDA 22-119/S-001","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022119orig1s001.pdf"},{"label":"ASNC/SNMMI PET nuclear cardiology procedure standard","url":"https://www.asnc.org/wp-content/uploads/2024/06/s12350-016-0522-3.pdf"}],"tags":["PET","myocardial perfusion","cyclotron"],"related":["rb-82-chloride","f-18-flurpiridaz","n-13","o-15","rb-82"],"indications":["coronary-artery-disease","cardiac-sarcoidosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"N-13 ammonia (as NH3/NH4+) diffuses into myocytes and is metabolically trapped as N-13 glutamine by glutamine synthetase, giving high myocardial uptake proportional to blood flow. Its 9.97-minute physical half-life requires an on-site cyclotron, in contrast to generator-produced Rb-82, but permits standard two- or three-compartment kinetic modelling for absolute myocardial blood flow quantification (mL/min/g) using dynamic PET acquisition.","approvals":[{"region":"US","year":2007,"indication":"Diagnostic PET imaging of the myocardium under rest or pharmacologic stress to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus injection","schedule":"10-20 mCi (0.368-0.736 GBq) per rest or stress study; imaging begins about 3 minutes after injection for 10-20 minutes; stress study begun 40+ minutes after the rest dose","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022119s001lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/n-13-ammonia/"}
{"id":"f-18-flurpiridaz","kind":"drug","name":"Flurpiridaz F-18","aka":["18F-flurpiridaz","BMS-747158-02"],"tldr":"The newest heart PET tracer, approved in the US in September 2024. It sticks tightly to a protein inside heart-muscle mitochondria in proportion to blood flow, lasts long enough to be made off site and shipped like a hospital's regular PET drug, and is the first cardiac PET tracer practical to pair with a treadmill exercise test.","summary":"Flyrcado (flurpiridaz F-18) is a fluorine-18 mitochondrial complex I-binding PET myocardial perfusion agent approved by the FDA on 27 September 2024 (NDA 215168, GE HealthCare), the first new PET MPI agent approved in the US in over a decade and the first cardiac PET tracer with a half-life practical for exercise stress protocols. Its mechanism, high-affinity binding to complex I rather than ion-pump uptake, gives a first-pass extraction fraction of about 94%, markedly higher and flatter across flow rates than sestamibi (55-68%), tetrofosmin (54%) or Rb-82 (roughly 40-70%), which its sponsor and independent reviews report translates into sharper contrast for smaller or milder perfusion defects.\n\nThe approved indication is PET myocardial perfusion imaging under rest or stress (pharmacologic or exercise) in adult patients with known or suspected coronary artery disease, to evaluate for myocardial ischaemia and infarction. Because F-18's 110-minute half-life is roughly ten times that of Rb-82 and eleven times N-13 ammonia's, Flyrcado can be manufactured off site and delivered as a ready-to-use unit dose like FDG, potentially widening PET MPI access beyond centres with an on-site generator or cyclotron, including for patients who are difficult to image by SPECT (high body-mass index, women with breast attenuation artefact).\n\nMost common adverse reactions in the pivotal programme (occurring in at least 2% of subjects across rest and stress imaging) were dyspnoea, headache, angina pectoris, chest pain, fatigue, ST-segment changes, flushing, nausea, abdominal pain, dizziness and arrhythmia. As a newly approved agent, real-world comparative outcome and cost-effectiveness data against SPECT and existing PET tracers are still accumulating.","asOf":"2026-09-22","links":[{"label":"FDA approval letter and package, NDA 215168 (Flyrcado)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/215168Orig1s000Approv.pdf"},{"label":"FDA label: Flyrcado (flurpiridaz F 18) injection, September 2024","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/215168s000lbl.pdf"},{"label":"FDA news release: FDA approves imaging drug for evaluation of myocardial ischemia and infarction (27 September 2024)","url":"https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-imaging-drug-evaluation-myocardial-ischemia-and-infarction"},{"label":"SNMMI/JNM procedure standard: 18F-flurpiridaz PET myocardial perfusion imaging and blood flow quantification","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2025/Flurpiridaz%20Procedure%20Standard-JNM.pdf"}],"tags":["PET","myocardial perfusion","mitochondrial complex I"],"related":["rb-82-chloride","n-13-ammonia","tc-99m-sestamibi","f-18","n-13","rb-82"],"indications":["coronary-artery-disease"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Flyrcado","modality":"PET tracer","mechanism":"Flurpiridaz F-18 is a fluorinated structural analogue of pyridaben, an insecticidal inhibitor of mitochondrial complex I (NADH:ubiquinone oxidoreductase). It binds with high affinity to complex I in cardiomyocyte mitochondria without impairing viability, giving a very high and largely flow-independent first-pass myocardial extraction fraction (reported at approximately 94% in preclinical and kinetic modelling studies) and slow washout, so uptake tracks blood flow more linearly across a wider flow range than the older SPECT or Rb-82 agents, with less roll-off at high flow. Its 110-minute F-18 half-life, more than ten times longer than Rb-82 or N-13 ammonia, allows off-site cyclotron production and unit-dose distribution like FDG, and is long enough to support exercise stress imaging, which is impractical with the shorter-lived PET perfusion tracers.","approvals":[{"region":"US","year":2024,"indication":"PET myocardial perfusion imaging (MPI) under rest or stress (pharmacologic or exercise) in adult patients with known or suspected coronary artery disease, to evaluate for myocardial ischaemia and infarction"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"Per FDA label dosing tables for rest and stress imaging (pharmacologic or exercise stress); supplied at 190-2,050 MBq/mL (5-55 mCi/mL) at end of synthesis","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/215168s000lbl.pdf"},"toxicity":[{"event":"Dyspnoea, headache, angina pectoris, chest pain, fatigue, ST-segment changes, flushing, nausea, abdominal pain, dizziness, arrhythmia (most common, combined rest and stress imaging)","source":"https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-imaging-drug-evaluation-myocardial-ischemia-and-infarction"}],"access":[],"regulatoryEvents":[{"date":"2024-09-27","type":"approval","region":"US","note":"FDA approved Flyrcado (flurpiridaz F 18) injection, NDA 215168, for PET myocardial perfusion imaging under rest or stress (pharmacologic or exercise) in adults with known or suspected CAD.","source":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/215168Orig1s000Approv.pdf"}],"route":"/drugs/f-18-flurpiridaz/"}
{"id":"tc-99m-pyrophosphate","kind":"drug","name":"Technetium Tc-99m pyrophosphate","aka":["Tc-99m PYP","PYP"],"tldr":"A bone-scanning radioactive tracer that also sticks to stray protein deposits that build up in a stiffened heart in transthyretin amyloidosis. Comparing how brightly the heart lights up against the ribs on the same scan tells doctors whether this specific, now-treatable type of heart disease is present, usually without needing a heart biopsy.","summary":"Technetium Tc-99m pyrophosphate (Technescan PYP, and generic/branded equivalents such as Phosphotec) is an old bone- and cardiac-imaging kit, FDA-approved for skeletal imaging of altered osteogenesis and, since the 1970s, as an adjunct in diagnosing acute myocardial infarction by direct uptake into necrotic tissue. Its label indications remain that dual scope (plus gated blood pool and gastrointestinal bleeding imaging via in vivo red blood cell labelling); it does not carry an FDA-labelled cardiac amyloidosis indication, and its use for that purpose is guideline-driven, off-label with respect to the original label wording, and now the dominant reason it is ordered in nuclear cardiology.\n\nThe evidence base for amyloid imaging is Gillmore et al. (2016, JAMA Cardiology, n=1,217: 857 with confirmed cardiac amyloidosis, 360 controls), which found 99% sensitivity and 86% specificity for ATTR cardiac amyloidosis using grade 2-3 myocardial uptake on planar/SPECT imaging, rising to 100% specificity and positive predictive value when combined with the absence of a monoclonal light-chain clone on serum/urine testing. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI multisociety expert consensus recommendations (with a 2021 addendum) formalised the protocol: SPECT or SPECT/CT confirmation of myocardial uptake is required (planar imaging alone is not diagnostic), typically read at both 1 hour and 3 hours after injection, with a visual grade of 2 or 3 classed as strongly suggestive of ATTR-CM, grade 1 as equivocal, and grade 0 as not suggestive.\n\nFDA labelled dosing for cardiac imaging is 370-555 MBq (10-15 mCi) intravenously, with imaging historically recommended 60-90 minutes post-injection for acute infarct detection; amyloid imaging protocols from the nuclear cardiology societies use similar activities with imaging windows out to 3 hours to reduce blood-pool interference.","asOf":"2026-09-22","links":[{"label":"FDA label: Technescan PYP (Tc-99m pyrophosphate), 2025 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/017538s023,018321s026lbl.pdf"},{"label":"Gillmore et al. 2016, JAMA Cardiology: multicentre study of Tc-99m PYP for ATTR cardiac amyloidosis","url":"https://jamanetwork.com/journals/jamacardiology/fullarticle/2546034"},{"label":"ASNC practice points: 99mTc-pyrophosphate imaging for cardiac amyloidosis","url":"https://www.asnc.org/wp-content/uploads/2024/05/ASNC-Practice-Point-99mTechnetium-Pyrophosphate.2016.pdf"}],"tags":["SPECT","cardiac amyloidosis","bone-avid tracer"],"related":["tl-201-chloride","tc-99m-sestamibi","tc-99m"],"indications":["cardiac-amyloidosis-attr"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Technescan PYP","modality":"SPECT tracer","mechanism":"Tc-99m pyrophosphate has a specific affinity for areas of altered osteogenesis (bone turnover) and, at lower concentration, for acutely infarcted myocardium and, incidentally, for transthyretin amyloid deposits in the heart, apparently via co-deposition of calcium/microcalcification within the amyloid fibrils. In cardiac amyloidosis imaging, myocardial retention is graded visually against rib (bone) uptake on a 0-3 scale on SPECT (or SPECT/CT) images obtained roughly 1-3 hours after injection; grade 2 (equal to rib) or grade 3 (greater than rib) uptake is considered positive.","approvals":[{"region":"US","year":1976,"indication":"Skeletal imaging to demonstrate areas of altered osteogenesis"},{"region":"US","year":1976,"indication":"Cardiac imaging as an adjunct in the diagnosis of acute myocardial infarction"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"Cardiac imaging (per FDA label): 370-555 MBq (10-15 mCi); cardiac amyloidosis SPECT protocols (per ASNC/multisociety guidance, off-label with respect to the original infarct indication) use similar activity with imaging at 1 and/or 3 hours","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/017538s023,018321s026lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-pyrophosphate/"}
{"id":"i-123-mibg-cardiac","kind":"drug","name":"Iobenguane I-123 (cardiac use)","aka":["I-123 MIBG","123I-mIBG"],"tldr":"A radioactive tracer that mimics the body's own \"fight or flight\" nerve chemical and is taken up by the nerve endings in heart muscle. In people with heart failure, comparing how much of it the heart holds onto against the surrounding chest tissue gives a read on how damaged the heart's nerve supply is, which relates to future risk.","summary":"AdreView (iobenguane I-123 injection) is a noradrenaline-analogue SPECT agent originally approved by the FDA in 2008 for detecting primary or metastatic phaeochromocytoma or neuroblastoma; a 2013 supplemental approval added a distinct cardiac indication (outside this record's oncology scope but the reason it is filed here as a cardiac agent): scintigraphic assessment of sympathetic innervation of the myocardium by measurement of the heart-to-mediastinum (H/M) uptake ratio in patients with NYHA class II or III heart failure and left ventricular ejection fraction 35% or less.\n\nIn this population, AdreView is labelled to help identify patients with lower one- and two-year mortality risk, indicated by an H/M ratio of 1.6 or greater (expected range 1.0-2.4); the label explicitly states its utility has not been established for selecting a therapeutic intervention, for monitoring response to therapy, or for identifying patients at high risk of death. The recommended adult dose is 10 mCi (370 MBq) by slow intravenous injection, with thyroid blockade (potassium iodide or perchlorate) beforehand to protect the thyroid from free iodine-123, and planar chest imaging beginning about 4 hours after injection, with optional SPECT.\n\nThis is a different mechanism and a different clinical question from the perfusion tracers in this file: it does not assess coronary blood flow or ischaemia, but the integrity of the heart's autonomic nerve supply, used as a risk-stratification adjunct in systolic heart failure rather than a coronary artery disease diagnostic.","asOf":"2026-09-22","links":[{"label":"FDA label: AdreView (iobenguane I 123 injection), 2020 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022290s005lbl.pdf"},{"label":"FDA approval letter: supplemental NDA 22-290/S-001 (cardiac heart failure indication, 2013)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/022290orig1s001ltr.pdf"}],"tags":["SPECT","sympathetic innervation","heart failure"],"related":["i131-mibg","iobenguane-i-131","mibg-theranostics","i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"AdreView","modality":"SPECT tracer","mechanism":"Iobenguane (metaiodobenzylguanidine, MIBG) is a noradrenaline analogue taken up by cardiac sympathetic nerve terminals through the same norepinephrine transporter (uptake-1) used by noradrenaline itself, then stored in neurosecretory vesicles. In failing hearts, sympathetic nerve terminals are damaged or down-regulated, reducing MIBG uptake and washout characteristics; the heart-to-mediastinum (H/M) uptake ratio on a planar image taken about 4 hours after injection quantifies how much sympathetic innervation remains, independent of coronary anatomy.","approvals":[{"region":"US","year":2008,"indication":"Detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests"},{"region":"US","year":2013,"indication":"Scintigraphic assessment of sympathetic innervation of the myocardium via heart-to-mediastinum ratio in NYHA class II-III heart failure with LVEF ≤ 35%, to help identify patients with lower 1- and 2-year mortality risk"}],"mechanismSteps":[],"dosing":{"route":"Slow intravenous injection over 1-2 minutes, after thyroid blockade","schedule":"10 mCi (370 MBq) for patients 16 years or older (or under 16 and ≥ 70 kg); weight-scaled dose for younger/lighter paediatric patients; planar chest imaging at about 4 hours post-injection, SPECT optional","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022290s005lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/i-123-mibg-cardiac/"}
{"id":"technegas","kind":"drug","name":"Technegas (technetium Tc-99m labelled carbon inhalation aerosol)","aka":["Technegas","Tc-99m carbon nanoparticle aerosol","99mTc-CNP"],"tldr":"A puff of radioactive carbon particles so fine they travel with the breath into the depths of the lung, where they stick. A gamma camera then photographs which parts of the lung are getting air, which is compared with a second scan showing which parts are getting blood.","summary":"Technegas is an inhaled ventilation agent generated at the bedside: a Technegas generator flash-heats dried Tc-99m pertechnetate in a carbon crucible at roughly 2,700 C in argon, producing technetium encapsulated in carbon nanoparticle agglomerates measured at 60-160 nm, themselves built from 7-23 nm primary particles, with a radioactivity aerodynamic diameter below 500 nm. That size is the point: unlike a wet aerosol such as Tc-99m DTPA, which impacts in the central airways and gives hot spots in obstructive disease, Technegas distributes to the lung periphery and holds still long enough to image in multiple projections.\n\nThe FDA approved Technegas on 29 September 2023 under NDA 022335, held by Cyclomedica Australia, after decades of use elsewhere. The approved indication is narrow and precise: used with sodium pertechnetate Tc-99m in the Technegas Plus System, it is a radioactive diagnostic agent for adults and paediatric patients aged 6 years and older for visualisation of pulmonary ventilation and evaluation of pulmonary embolism when paired with perfusion imaging. Dosing is count-rate driven rather than fixed: 400-1,000 MBq (10.8-27 mCi) is loaded in the crucible to reach a lung count rate of 1,500-2,500 counts per second for adults, 500-1,000 for children, with inhalation completed within 10 minutes of preparation.\n\nThe US registration study, CYC-009 (NCT03054870), was a phase 3 non-inferiority comparison against xenon-133 planar ventilation imaging; its ClinicalTrials.gov record shows 226 participants actually enrolled and a terminated status. The label itself specifies imaging with a gamma camera and a low-energy collimator and does not use the words SPECT or planar, though the agent's stability in the lung is exactly what makes V/Q SPECT practical, and the EANM V/Q SPECT guideline is built around it.","status":"approved","asOf":"2026-09-23","links":[{"label":"FDA label: TECHNEGAS, kit for the preparation of technetium Tc 99m labeled carbon inhalation aerosol (NDA 022335)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022335Orig1s000lbl.pdf"},{"label":"FDA approval package, NDA 022335, approval date 29 September 2023","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/022335Orig1s000Approv.pdf"},{"label":"Technegas particle characterisation: nanoparticle agglomerates of 60-160 nm (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10144982/"},{"label":"Cyclomedica: FDA grants approval for Technegas","url":"https://www.cyclomedica.com/2023/10/02/united-states-fda-grants-approval-for-technegas/"}],"tags":["ventilation","V/Q","technetium","inhaled"],"related":["tc-99m-maa","kr-81m","tc-99m","pulmonary-embolism-vq","cyclopharm","spect"],"indications":["pulmonary-embolism-vq"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03054870"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Technegas","modality":"Inhaled SPECT/gamma camera aerosol","mechanism":"Dried sodium pertechnetate Tc-99m is loaded into a graphite crucible and flash-heated to about 2,700 C for a few seconds in high-purity argon, which encapsulates the technetium inside carbon. The product is an ultrafine dispersion of carbon nanoparticle agglomerates with a radioactivity aerodynamic diameter under 500 nm, small enough to behave much like a gas: it follows inspired air to the alveoli rather than impacting in the large airways, then deposits and stays put, so the image is a map of where air actually reaches. Made with an argon/oxygen mix instead, the same generator yields Pertechnegas, whose technetium is not fully encased and which clears rapidly as soluble pertechnetate.","approvals":[{"region":"US","year":2023,"indication":"Visualisation of pulmonary ventilation, and evaluation of pulmonary embolism when paired with perfusion imaging, in adults and children aged 6 and over","note":"NDA 022335, Cyclomedica Australia, approved 29 September 2023"}],"mechanismSteps":[],"dosing":{"route":"Oral inhalation of the generated aerosol through a mouthpiece","schedule":"400-1,000 MBq (10.8-27 mCi) of Tc-99m pertechnetate loaded in the crucible for adults, inhaled by slow deep breathing with a 5-second breath-hold until a lung count rate of 1,500-2,500 counts per second is reached; 500-1,000 counts per second for children aged 6 and over. Inhalation must be completed within 10 minutes of preparation.","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022335Orig1s000lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2023-09-29","type":"approval","region":"US","note":"FDA approval of NDA 022335 (Cyclomedica Australia), Type 3 new dosage form","source":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/022335Orig1s000Approv.pdf"}],"route":"/drugs/technegas/"}
{"id":"tc-99m-maa","kind":"drug","name":"Technetium Tc-99m albumin aggregated (MAA)","aka":["99mTc-MAA","Tc-99m macroaggregated albumin","MAA","Pulmotech MAA","DraxImage MAA"],"tldr":"Tiny clumps of albumin, a normal blood protein, tagged with a radioactive marker and injected into a vein. They wedge briefly in the smallest blood vessels of the lung wherever blood is flowing, so the scan maps the lung's blood supply; the clumps then break up and clear.","summary":"Tc-99m macroaggregated albumin is the perfusion half of the V/Q scan and one of the oldest radiopharmaceuticals still in routine use. Two products are marketed in the US: Pulmotech MAA (BLA 210089, CIS bio International, distributed by Curium, initial US approval 2020) and DraxImage MAA (BLA 017881, Jubilant DraxImage, initial US approval 1987). Both carry the same two indications: lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion in adults and paediatric patients, and peritoneovenous shunt scintigraphy as an aid in evaluating its patency.\n\nDosing is by particle count rather than activity alone. An adult dose is 200,000 to 700,000 particles, about 350,000 recommended, falling to 10,000-50,000 for neonates under four weeks, because each particle occludes a capillary and the margin of safety comes from how few of them there are relative to the pulmonary capillary bed. The labels contraindicate the agent in severe pulmonary hypertension, where deaths have been reported, and in albumin hypersensitivity.\n\nIts second life is in interventional oncology. Before yttrium-90 radioembolisation, MAA is injected into the hepatic artery and imaged to estimate the lung shunt fraction, because hepatopulmonary shunting can deliver enough dose to the lungs to cause radiation pneumonitis. The dose constraint usually applied is a lung mean dose of 30 Gy from a single treatment or 50 Gy cumulative, and a shunt fraction above 20% has traditionally contraindicated resin-microsphere treatment. MAA is used as the surrogate because its particles are close in size to the microspheres, though the correspondence is imperfect and is itself an active research question.","status":"approved","asOf":"2026-09-23","links":[{"label":"FDA label: PULMOTECH MAA (BLA 210089), revised August 2023","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210089s002lbl.pdf"},{"label":"FDA label: DRAXIMAGE MAA (BLA 017881), revised December 2023","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/017881s030lbl.pdf"},{"label":"Kappadath et al.: lung shunt fraction from 99mTc-MAA SPECT/CT for Y-90 treatment planning, with the 30 Gy single and 50 Gy cumulative lung dose constraints","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8479035/"}],"tags":["perfusion","V/Q","technetium","radioembolisation work-up"],"related":["technegas","kr-81m","split-function-lung-perfusion","tc-99m","pulmonary-embolism-vq","y-90-resin-microspheres","y-90-glass-microspheres","radioembolisation-tare","curium","jubilant-radiopharma","y-90"],"indications":["pulmonary-embolism-vq"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"Intravenous SPECT particle agent","mechanism":"Human albumin is heat-aggregated into particles of which more than 90% measure 10-90 micrometres, none above 150. Injected intravenously, they are carried to the lungs and physically lodge in pulmonary arterioles and capillaries in proportion to regional blood flow: over 90% are trapped within 1 to 5 minutes, occluding a tiny fraction of the pulmonary capillary bed. The blockade is temporary because the aggregates are fragile and break up, and the resulting image is a perfusion map. Injected instead into the hepatic artery, the same particles follow the route Y-90 microspheres will take, which is what makes them a usable simulation of a radioembolisation treatment.","approvals":[{"region":"US","year":1987,"indication":"Lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion, and peritoneovenous shunt patency","note":"DraxImage MAA, BLA 017881, Jubilant DraxImage"},{"region":"US","year":2020,"indication":"Lung scintigraphy as an adjunct in the evaluation of pulmonary perfusion, and peritoneovenous shunt patency","note":"Pulmotech MAA, BLA 210089, CIS bio International, distributed by Curium"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection for lung perfusion; intra-arterial (hepatic artery) for radioembolisation work-up","schedule":"Adults 200,000-700,000 particles per injection, approximately 350,000 recommended; paediatric doses reduced by age, 10,000-50,000 particles for neonates under four weeks","modifications":"Contraindicated in severe pulmonary hypertension and in albumin hypersensitivity; reduce particle number in right-to-left shunt","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210089s002lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-maa/"}
{"id":"pb-212-psv359","kind":"drug","name":"Lead-212 PSV359","aka":["[212Pb]PSV359","PSV359","PSV377 (imaging analogue)"],"tldr":"A drug that homes to the scaffolding cells tumours build around themselves, carrying a radioactive metal that fires alpha particles over a very short range. A matching scan version shows first whether a patient's tumour has the target.","summary":"PSV359 is Perspective Therapeutics' lead-212 radioligand against fibroblast activation protein alpha, the marker of cancer-associated fibroblasts. FAP-alpha is attractive because it is present in the stroma of most epithelial cancers and nearly absent from normal adult tissue, and because high expression tracks with poor prognosis in non-small cell lung, colorectal, pancreatic, gastric, mesothelioma, head and neck, oesophageal and ovarian cancers.\n\nThe first-in-human phase 1/2 study, NCT06710756, opened in April 2025 with a planned 112 participants and uses the pair directly: [203Pb]PSV359 to image and [212Pb]PSV359 to treat. Its original tumour list was pancreatic, gastric and gastro-oesophageal junction, oesophageal, colorectal and ovarian cancer and head and neck squamous cell carcinoma. On 14 September 2026 Perspective announced a clinical collaboration and supply agreement with Merck under which the trial is amended to add cohorts combining [212Pb]PSV359 with pembrolizumab in FAP-alpha-positive non-small cell lung cancer and colorectal cancer. That amendment is what puts an alpha-emitting radioligand into NSCLC, a tumour that radiopharmaceuticals have otherwise reached only as a diagnostic.\n\nPerspective guides initial phase 1/2a data in late 2026. Nothing has been published on activity in lung cancer, and the pipeline table still lists the programme's target disease simply as solid tumours.","status":"phase-1","asOf":"2026-09-23","links":[{"label":"Perspective Therapeutics: clinical collaboration and supply agreement with Merck to evaluate [212Pb]PSV359 with Keytruda in FAP-alpha positive solid tumours, 14 September 2026","url":"https://www.perspectivetherapeutics.com/pr/perspective-therapeutics-announces-clinical-collaboration-and-supply-agreement-with-merck-to-evaluate-212pbpsv359-in-combination-with-keytruda-pembrolizumab-in-fap-a-positive-solid-tumors"},{"label":"ClinicalTrials.gov NCT06710756: lead-212 PSV359 therapy for patients with solid tumours","url":"https://clinicaltrials.gov/study/NCT06710756"},{"label":"Perspective Therapeutics pipeline","url":"https://www.perspectivetherapeutics.com/pipeline/"}],"tags":["FAP","lead-212","alpha","NSCLC"],"related":["perspective-therapeutics","fap","fapi-pet","pb-212","pb-212-vmt-alpha-net","targeted-alpha-therapy","nsclc","merck","pembrolizumab"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06710756"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"PSV359","modality":"Alpha-emitting radioligand (FAP-alpha targeted)","mechanism":"A small-molecule ligand for fibroblast activation protein alpha, the protease on the cancer-associated fibroblasts that build the stroma of most epithelial tumours, carrying lead-212 as the payload. Lead-212 decays through bismuth-212 to deliver an alpha particle, depositing its energy over a few cell diameters, so the dose lands on the stromal scaffold and the tumour cells packed against it rather than on distant marrow. The same targeting molecule labelled with lead-203 or gallium-68, designated PSV377, images FAP-alpha expression, so a patient can be selected on a scan before being treated.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/pb-212-psv359/"}
{"id":"nct03054870","kind":"trial","name":"CYC-009: Technegas versus xenon-133 ventilation imaging","aka":[],"tldr":"The trial that got Technegas approved in the United States: it compared the inhaled carbon aerosol against xenon-133 gas, the agent it was meant to replace.","summary":"CYC-009 (NCT03054870) was a phase 3 non-inferiority study run by Cyclomedica Australia under IND 62660, comparing Technegas with xenon-133 planar lung imaging in patients referred for ventilation scintigraphy. Its stated primary objective was to demonstrate non-inferiority of Technegas to xenon-133 with respect to the distribution of pulmonary ventilation. The registry lists the study as terminated with an actual enrolment of 226. Cyclomedica's own history records the trial completing and the New Drug Application being submitted in 2020; the FDA approved NDA 022335 on 29 September 2023.","status":"historic","asOf":"2026-09-23","links":[{"label":"ClinicalTrials.gov NCT03054870","url":"https://clinicaltrials.gov/study/NCT03054870"},{"label":"CYC-009 protocol and statistical analysis plan (ClinicalTrials.gov document)","url":"https://cdn.clinicaltrials.gov/large-docs/70/NCT03054870/Prot_SAP_001.pdf"}],"tags":["ventilation","registration trial"],"related":["technegas","cyclopharm","pulmonary-embolism-vq"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["technegas"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03054870","phase":"3","setting":"Adults referred for ventilation scintigraphy, imaged with both Technegas and xenon-133 by planar technique, to test whether Technegas is non-inferior to xenon-133 for the distribution of pulmonary ventilation. This is the registration study behind the 2023 US approval; ClinicalTrials.gov records its status as terminated with 226 participants actually enrolled.","sponsor":"Cyclomedica Australia","enrolled":226,"enrolledBasis":"registry","outcomes":[],"route":"/trials/nct03054870/"}
{"id":"kr-81m","kind":"isotope","name":"Krypton-81m","aka":["81mKr","Kr-81m","krypton gas"],"tldr":"A radioactive gas that a patient simply breathes in and out while the camera runs. It decays in thirteen seconds, so the picture is of ventilation happening now rather than of particles left behind, and it has to be generated in the room from a parent that itself lasts only a few hours.","summary":"Krypton-81m is an inert gas with a 13-second physical half-life and a 190 keV gamma emission, eluted from an 81Rb/81mKr generator: rubidium-81, bound to a zirconium phosphate cation exchange resin, sits in equilibrium with its krypton daughter, and passing oxygen or air through the generator carries the gas to the patient. The patient inhales continuously through the acquisition, so the image is a steady-state map of where air is arriving, and because the activity vanishes between views the study can be repeated in as many projections as wanted with negligible dose.\n\nIts distinctive advantage is the 190 keV photon, well separated from technetium-99m's 140 keV, which means ventilation and perfusion can be acquired simultaneously rather than sequentially. The 2019 EANM V/Q SPECT guideline puts krypton alongside Technegas as preferred over Tc-99m DTPA aerosol in patients with COPD, where a wet aerosol deposits centrally, and one comparative review argues krypton is the better ventilation tracer for its penetration and absence of hot spots, cautioning against replacing it with Technegas in severe COPD. The counterweight is that in badly obstructed lungs the time to reach steady state may be too long.\n\nAvailability is the whole problem. Rubidium-81 is cyclotron-made, principally by the 82Kr(p,2n)81Rb reaction, and has a half-life of about 4.6 hours, so a generator has to be delivered to the hospital daily from a nearby cyclotron. That economics confined krypton to a handful of countries: Kr-81m/Tc-99m V/Q imaging was once, by one account, the second most performed nuclear medicine procedure in the United Kingdom after bone scanning, and a generator remains licensed in Denmark by Rigshospitalet's own cyclotron. In the United States GE Healthcare's MPI Krypton 81m generator (NDA 018088, approved 1980) was withdrawn effective 7 December 2007, and US commercial availability had already ended years earlier.","status":"historic","asOf":"2026-09-23","links":[{"label":"EANM 2019 guideline for ventilation/perfusion SPECT (krypton and Technegas preferred over DTPA in COPD; 13 s half-life, 190 keV, simultaneous acquisition with Tc-99m)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6813289/"},{"label":"Comparative review: krypton-81m versus Technegas for ventilation imaging in COPD","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7808361/"},{"label":"IAEA evaluated nuclear data for 81Rb production, 82Kr(p,2n)81Rb, parent half-life 4.572 h","url":"http://arxiv.org/pdf/2006.03125"},{"label":"Ventilation studies with krypton-81m: continuous-flow elution and repeated projections","url":"https://pubmed.ncbi.nlm.nih.gov/542943/"}],"tags":["ventilation","V/Q","generator","gas"],"related":["technegas","tc-99m-maa","tc-99m","pulmonary-embolism-vq","split-function-lung-perfusion"],"indications":["pulmonary-embolism-vq"],"sections":[],"technologies":["spect","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"81mKr","element":"Krypton","massNumber":81,"halfLife":"13 seconds","emissions":["γ 190 keV"],"emissionClass":"gamma","use":"imaging","production":"Generator: decay of cyclotron-produced rubidium-81 (half-life about 4.6 hours) adsorbed on zirconium phosphate resin, made principally by the 82Kr(p,2n)81Rb reaction; the gas is eluted by a continuous flow of oxygen or air and inhaled directly.","supply":"constrained","supplyNote":"The parent's 4.6-hour half-life forces daily delivery from a cyclotron within a few hours' reach, which is why use is confined to a few centres and countries. The only US product, GE Healthcare's MPI Krypton 81m generator (NDA 018088, 1980), was formally withdrawn effective 7 December 2007. A generator authorisation is held in Denmark by the cyclotron and radiochemistry unit at Rigshospitalet, Copenhagen.","chelators":[],"pairedWith":["tc-99m"],"route":"/isotopes/kr-81m/"}
{"id":"split-function-lung-perfusion","kind":"technology","name":"Split-function perfusion scintigraphy before lung resection","aka":["Quantitative lung perfusion scintigraphy","Split lung function study","Differential perfusion scan"],"tldr":"Before a surgeon removes part of a lung, the scan is used as an arithmetic tool rather than a picture: it measures what share of the breathing work that piece of lung is actually doing, so the team can predict the patient's lung function after the operation and decide whether they will tolerate it.","summary":"Predicting postoperative lung function is where perfusion scintigraphy earns its place in thoracic oncology. The ACCP physiologic evaluation guideline (Brunelli et al., Chest 2013) sets out the division of labour explicitly: for a pneumonectomy candidate the perfusion method is used, with predicted postoperative FEV1 taken as preoperative FEV1 times one minus the fraction of total perfusion for the resected lung, while for a lobectomy the anatomical segment-counting method is used. The reason is empirical, not dogmatic: before lobectomy, segment counting predicts postoperative FEV1 about as well as scintigraphy, so the scan is usually unnecessary; before pneumonectomy, the lung to be removed has to be measured.\n\nThe thresholds are what make the scan consequential. The ACCP guideline recommends no further testing when both predicted postoperative FEV1 and DLCO exceed 60% of predicted; a low-technology exercise test (stair climb or shuttle walk) when either falls below 60% but both stay above 30%; and formal cardiopulmonary exercise testing with VO2max measurement when either falls below 30%. The ERS/ESTS 2009 guideline routes any patient whose FEV1 or DLCO is below 80% of predicted to cardiopulmonary exercise testing, and regards predicted postoperative FEV1 or DLCO below 30% combined with a peak VO2 below 35% of predicted or 10 mL/kg/min as prohibitive risk for major resection. In its framing, segment counting is the default calculation and perfusion scintigraphy is reserved for patients whose function is borderline.\n\nWhether tomographic quantification beats planar counting is genuinely unsettled. A 2024 series found SPECT/CT predicted postoperative FEV1 and DLCO more accurately than either planar scintigraphy or segment counting, and would have qualified 58 of 82 patients for resection against 47 by segment counting. A 2020 head-to-head study in the Journal of Nuclear Medicine found no significant difference between segment counting, planar perfusion and SPECT/CT, and concluded the extra effort may add nothing outside right lobectomy. What both agree on is the direction of the error in segment counting: it systematically underestimates postoperative function, which risks denying surgery to patients who would have tolerated it.","status":"standard-of-care","asOf":"2026-09-23","links":[{"label":"ACCP physiologic evaluation of the patient with lung cancer being considered for resectional surgery (Brunelli et al., Chest 2013): the ppo formulas and the 60% and 30% thresholds","url":"https://www.aamr.org.ar/secciones/oncologia/evaluacion_fisiologica.pdf"},{"label":"ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (Brunelli et al. 2009)","url":"https://academic.oup.com/ejcts/article/36/1/181/2755225"},{"label":"Fitness for radical treatment of lung cancer patients (Breathe 2011): why segment counting suffices before lobectomy","url":"https://publications.ersnet.org/content/breathe/7/3/221"},{"label":"SPECT/CT quantification predicted postoperative FEV1 and DLCO better than planar or segment counting (2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11509096/"},{"label":"Head-to-head comparison finding no significant difference between segment counting, planar perfusion and SPECT/CT (J Nucl Med 2020)","url":"https://jnm.snmjournals.org/content/61/7/981"}],"tags":["pulmonary","surgical planning","quantitative","SPECT"],"related":["tc-99m-maa","kr-81m","pulmonary-embolism-vq","nsclc"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["tc-99m-maa"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"The same Tc-99m MAA perfusion scan used to look for embolism, counted rather than merely looked at. Activity is measured per lung (and per region on tomographic studies) to give the fraction of total perfusion each part contributes, and that fraction is used to predict what spirometry will look like after a resection: predicted postoperative FEV1 equals preoperative FEV1 multiplied by one minus the fraction of total perfusion belonging to the lung to be removed. For a lobectomy the anatomical version is used instead, multiplying by one minus the number of unobstructed segments to be removed over the total number of unobstructed segments, counting 19 segments in all.","strengths":["Turns a routine perfusion scan into a quantitative decision tool, using a formula stated in guidelines rather than judgement.","Measures what the lung to be resected actually contributes, which matters most when disease has already destroyed function in that lung; segment counting assumes every segment is equal.","Segment counting systematically underestimates predicted postoperative FEV1, so the scan can qualify patients for curative surgery who would otherwise be refused."],"limitations":["Before a lobectomy it adds little: segment counting predicts postoperative FEV1 about as accurately, so guidelines reserve the scan for pneumonectomy candidates and borderline function.","Whether SPECT or SPECT/CT quantification beats planar counting is contested, with a 2024 series favouring SPECT/CT and a 2020 head-to-head study finding no difference.","It predicts spirometry, not outcome: the guidelines pair it with exercise testing precisely because a predicted value alone does not decide operability."],"route":"/technologies/split-function-lung-perfusion/"}
{"id":"cyclopharm","kind":"company","name":"Cyclopharm","aka":["Cyclomedica","Cyclomedica Australia","Cyclopharm Limited"],"tldr":"The Australian company behind Technegas, the inhaled ventilation agent, which spent thirty years as a product the United States could not buy and is now being installed across American hospitals.","summary":"Cyclopharm Limited (ASX:CYC) develops and sells Technegas through its operating company Cyclomedica Australia, which shares its Kingsgrove registered address. Technegas is used in 65 countries by the company's own count, with direct distribution in 17 and more than 5 million patient procedures to date.\n\nThe company's defining event was the US FDA approval of Technegas on 29 September 2023 under NDA 022335, opening the last major market that had been closed to it. Its first-half 2026 results reported US Technegas revenue up 74% year on year, from A$1.2m to A$2.1m, with revenue-generating US sites doubling from 35 at 30 June 2025 to 70 at 30 June 2026 and 83 by 12 August 2026, against a stated US lung imaging market of 5,139 sites. In July 2026 it announced a commercial installation across 11 clinical locations of University Hospitals in Cleveland, Ohio. Those commercial figures come from the company's own investor material rather than an independent source.\n\nWhat makes Cyclopharm structurally unusual in this corpus is that it sells a generator and a consumable rather than a dose: the value sits in the installed base of Technegas systems, not in isotope supply, so its constraint is hospital adoption and reimbursement rather than reactor time.","asOf":"2026-09-23","links":[{"label":"Cyclomedica: part of Cyclopharm Limited (ASX:CYC), 65 countries","url":"https://www.cyclomedica.com/company/cyclopharm/"},{"label":"Cyclopharm first-half 2026 results summary (investor presentation: 67 countries, 83 US revenue-generating sites as at 12 August 2026)","url":"https://investor.cyclopharm.com/site/pdf/ee402a7a-7ffe-4386-9541-9d22f3e60b42/Platform/ListPage/CYC-1H2026-Results-Summary.pdf"},{"label":"Cyclopharm ASX announcement: 11-site Technegas rollout at University Hospitals, Cleveland, 15 July 2026","url":"https://investor.cyclopharm.com/site/pdf/60334760-9465-4ad1-9ff3-1d17eb39d00c/Platform/ListPage/Immediate-11Site-Technegas-Rollout-at-University-Hospitals.pdf"}],"tags":["ventilation","Australia","listed"],"related":["technegas","pulmonary-embolism-vq","tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Kingsgrove, New South Wales, Australia","country":"AU","companyType":"radiopharma","website":"https://www.cyclopharm.com/","ticker":"ASX:CYC","stage":"public","investors":[],"funding":[],"route":"/companies/cyclopharm/"}
{"id":"asnc","kind":"institution","name":"American Society of Nuclear Cardiology","aka":["ASNC"],"tldr":"The professional society for heart scans that use radioactive tracers. It writes the rules for how those scans are done in the United States and publishes the field's journal.","summary":"ASNC describes itself as \"the international home for nuclear cardiology and the only professional society devoted exclusively to the field\", and dates its work to 1993. Its remit is the cardiac half of nuclear medicine: myocardial perfusion imaging with SPECT and PET, transthyretin cardiac amyloidosis imaging, cardiac sarcoidosis, and sympathetic innervation imaging - the clinical questions behind technetium-99m sestamibi, rubidium-82, nitrogen-13 ammonia, fluorine-18 flurpiridaz, technetium-99m pyrophosphate and iodine-123 MIBG.\n\nTwo outputs matter to this corpus. First, the appropriate use criteria and imaging guidelines ASNC issues with SNMMI and the ACC, which govern tracer choice and interpretation in US practice. Second, the Journal of Nuclear Cardiology (id: journal-of-nuclear-cardiology), its official journal, published by Elsevier: the Annual Scientific Session abstracts are deposited there each year, and because they carry no supplement label, Nuclide's congress harvest finds them by date window instead (scripts/fetch-abstracts.ts). The 2026 Annual Scientific Session ran 16 to 19 September in Las Vegas.","asOf":"2026-09-22","links":[{"label":"About ASNC","url":"https://www.asnc.org/about-asnc/"},{"label":"Journal of Nuclear Cardiology (official journal)","url":"https://www.asnc.org/news-publications/journal-of-nuclear-cardiology/"},{"label":"ASNC2026 Annual Scientific Session, 16 to 19 September 2026, Las Vegas","url":"https://www.asnc.org/education-events/annual-scientific-session/"}],"tags":[],"related":["journal-of-nuclear-cardiology","coronary-artery-disease","cardiac-amyloidosis-attr","cardiac-sarcoidosis","snmmi","f-18","tc-99m","i-123","n-13","rb-82"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Fairfax","country":"US","lat":38.8462,"lng":-77.3064,"institutionType":"consortium","website":"https://www.asnc.org/","programs":["Nuclear cardiology appropriate use criteria","Imaging guidelines and procedure standards","Annual Scientific Session"],"route":"/institutions/asnc/"}
{"id":"jsnm","kind":"institution","name":"Japanese Society of Nuclear Medicine","aka":["JSNM","Nihon Kaku Igakukai"],"tldr":"Japan's national society for nuclear medicine: it runs the country's annual nuclear medicine meeting and publishes its journals.","summary":"The JSNM was established in 1964 and states a membership of about 3,600. It publishes two journals: Annals of Nuclear Medicine (id: annals-of-nuclear-medicine), its English-language journal, and the Japanese-language Kaku Igaku. Its annual scientific meeting is the main venue for Japanese nuclear medicine data: the 66th meeting runs 19 to 21 November 2026 in Himeji and the 67th on 11 to 13 November 2027 in Omiya.\n\nJapan matters to this corpus for two reasons that its society meetings track directly. Approvals arrive later than in the US or EU but are well documented in English by the PMDA - Lutathera in June 2021, Pluvicto and Locametz in September 2025. And Japan is import-dependent for the molybdenum-99 that feeds its technetium-99m generators, which makes domestic isotope supply a standing agenda item rather than a background concern.","asOf":"2026-09-22","links":[{"label":"About the JSNM (established 1964, about 3,600 members)","url":"https://jsnm.org/english/about_jsnm/"},{"label":"JSNM publications","url":"https://jsnm.org/english/publications/"},{"label":"JSNM meetings and events (66th 2026 Himeji, 67th 2027 Omiya)","url":"https://jsnm.org/english/meetings_and_events/"}],"tags":[],"related":["annals-of-nuclear-medicine","pdradiopharma","nihon-medi-physics","pmda","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Tokyo","country":"JP","lat":35.6595,"lng":139.7247,"institutionType":"consortium","website":"https://jsnm.org/english/","programs":["Annual scientific meeting","Annals of Nuclear Medicine","Kaku Igaku"],"route":"/institutions/jsnm/"}
{"id":"ksnm","kind":"institution","name":"Korean Society of Nuclear Medicine","aka":["KSNM"],"tldr":"South Korea's nuclear medicine society, which runs the country's annual meeting and publishes its English-language journal.","summary":"The KSNM describes itself as \"a scientific and professional organization founded in 1961\". Its journal is Nuclear Medicine and Molecular Imaging (id: nuclear-medicine-and-molecular-imaging), published by Springer. The 65th annual meeting, held with the 25th Asian Regional Cooperative Council for Nuclear Medicine meeting, runs 6 to 7 November 2026 at Sejong University in Seoul.\n\nKorea is a small market with an unusually dense radiopharmaceutical industry: FutureChem's florastamin F-18 PSMA tracer reached MFDS approval in April 2026, CellBion has filed for conditional approval of a lutetium-177 PSMA therapy, DuChemBio supplies most of the country's diagnostic tracers, and KIRAMS runs the public cyclotron and alpha-emitter programmes. The society meeting is where those programmes report first.","asOf":"2026-09-22","links":[{"label":"KSNM English site (founded 1961; 65th annual meeting 6 to 7 November 2026, Sejong University, Seoul)","url":"https://www.ksnm.or.kr/eng/"},{"label":"KSNM publication archive","url":"https://www.ksnm.or.kr/eng/pub/search.php"}],"tags":[],"related":["nuclear-medicine-and-molecular-imaging","futurechem","cellbion","duchembio","kirams","f-18","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Seoul","country":"KR","lat":37.5665,"lng":126.978,"institutionType":"consortium","website":"https://www.ksnm.or.kr/eng/","programs":["Annual meeting","Nuclear Medicine and Molecular Imaging"],"route":"/institutions/ksnm/"}
{"id":"csnm","kind":"institution","name":"Chinese Society of Nuclear Medicine","aka":["CSNM","Chinese Medical Association Society of Nuclear Medicine"],"tldr":"China's national nuclear medicine society, a branch of the Chinese Medical Association, which runs the country's annual nuclear medicine congress.","summary":"The society publishes in Chinese as a branch of the Chinese Medical Association and gives its own English name on its site as the Chinese Society of Nuclear Medicine. Its 2026 congress - the 19th National Nuclear Medicine Academic Conference, held with the field's 70th anniversary in China - ran 17 to 19 September 2026 in Xi'an, per the society's own banner (English title as given by the society).\n\nIt is the publishing body behind the Chinese Journal of Nuclear Medicine and Molecular Imaging (id: chinese-journal-of-nuclear-medicine-and-molecular-imaging), which is the main Chinese-language venue for the field and is not indexed in Crossref, so its content cannot be harvested the way the Western journals are. Chinese radiopharmaceutical research output is instead tracked here through Europe PMC affiliation counts (scripts/fetch-global.ts) and through worldwide patent filings (scripts/fetch-patents.ts), both of which return English text.","asOf":"2026-09-22","links":[{"label":"Chinese Society of Nuclear Medicine (Chinese Medical Association)","url":"https://chinanm.cma.org.cn/"},{"label":"Chinese Journal of Nuclear Medicine and Molecular Imaging, 2026 issue 3 contents","url":"https://chinanm.cma.org.cn/art/2026/4/22/art_1509_60533.html"}],"tags":[],"related":["chinese-journal-of-nuclear-medicine-and-molecular-imaging","china-isotope-radiation","sinotau-pharmaceutical"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Beijing","country":"CN","lat":39.9042,"lng":116.4074,"institutionType":"consortium","website":"https://chinanm.cma.org.cn/","programs":["National Nuclear Medicine Academic Conference","Chinese Journal of Nuclear Medicine and Molecular Imaging"],"route":"/institutions/csnm/"}
{"id":"kirams","kind":"institution","name":"Korea Institute of Radiological and Medical Sciences","aka":["KIRAMS"],"tldr":"South Korea's government radiation-medicine institute, which runs the national cancer hospital and the cyclotrons that make the country's research isotopes.","summary":"KIRAMS is a government-funded research institute combining radiological research with the Korea Cancer Center Hospital, which has operated since 1963. Its cyclotrons supply research isotopes to Korean groups, and in 2025 it was reported to have received approval from Korea's Nuclear Safety and Security Commission to begin cyclotron production of actinium-225, the alpha emitter behind the next generation of radioligand therapies. That approval is reported here from an English-language news account rather than a KIRAMS page, and is flagged as such.\n\nKIRAMS also convenes the national alpha-radiopharmaceutical research consortium with Korean industry, which is how the state institute and the listed developers (FutureChem, CellBion) coordinate on isotope supply.","asOf":"2026-09-22","links":[{"label":"Korea Cancer Center Hospital (KIRAMS), history from 1963","url":"https://www.kcch.re.kr/eng/conts/101001000000000.do"},{"label":"News report: KIRAMS approved to produce actinium-225 (Asia Business Daily English edition, June 2025)","url":"https://view.asiae.co.kr/en/article/2025060415574246814"}],"tags":[],"related":["ac-225","cellbion","futurechem","ksnm"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Seoul","country":"KR","lat":37.6396,"lng":127.0594,"institutionType":"research-institute","website":"https://www.kirams.re.kr/","programs":["Cyclotron isotope production","Korea Cancer Center Hospital","Alpha-emitter research"],"route":"/institutions/kirams/"}
{"id":"brit","kind":"institution","name":"Board of Radiation and Isotope Technology","aka":["BRIT"],"tldr":"India's government isotope producer: it makes and sells the radioactive medicines used in Indian hospitals.","summary":"BRIT is a unit of India's Department of Atomic Energy and the country's main supplier of radiopharmaceuticals. Its own therapeutic product page lists sodium iodide I-131, I-131 mIBG, lutetium-177 EDTMP, lutetium-177 DOTATATE and lutetium-177 PSMA-617 injection in production - which means India manufactures domestically the same PSMA radioligand therapy that is sold in the West as Pluvicto, at a scale set by public supply rather than by a marketing authorisation.\n\nThe practical constraint is feedstock: India is not self-sufficient in molybdenum-99 or iodine-131, so hospital supply depends on reactor availability and imports. BRIT's site is intermittently unreachable from outside India, so the product list above was read in a browser session on 22 September 2026 rather than by an automated fetch, and the regulator route (CDSCO's approved-new-drugs PDFs) blocks scripts entirely.","asOf":"2026-09-22","links":[{"label":"BRIT therapeutic radiopharmaceuticals product list","url":"https://britatom.gov.in/en/product/radiopharmaceuticals/therapeutic"},{"label":"BRIT (Department of Atomic Energy)","url":"https://britatom.gov.in/"}],"tags":[],"related":["lu-177","i-131","radioactive-iodine","aiims-delhi","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"city":"Navi Mumbai","country":"IN","lat":19.033,"lng":73.0297,"institutionType":"government","website":"https://britatom.gov.in/","programs":["Radiopharmaceutical production","Radioisotope supply to Indian hospitals"],"route":"/institutions/brit/"}
{"id":"nihon-medi-physics","kind":"company","name":"Nihon Medi-Physics","aka":["Nihon Medi-Physics Co., Ltd.","NMP"],"tldr":"Japan's largest maker of radioactive tracers for scans, now wholly owned by GE HealthCare.","summary":"Nihon Medi-Physics was incorporated on 20 March 1973 and is based at Shinsuna, Koto-ku, Tokyo. Its stated business is the \"research, development, manufacture, sale, purchase and import/export of radioactive pharmaceuticals\". It holds the Japanese approvals for several of the diagnostic agents in this corpus, each dated in the PMDA's own English list: DaTscan (ioflupane I-123) in September 2013, Vizamyl (flutemetamol F-18) in September 2017 and Axumin (fluciclovine F-18) in March 2021.\n\nOwnership changed in 2025. GE HealthCare had held 50 per cent since acquiring Amersham in 2004; on 31 March 2025 it completed the purchase of the remaining 50 per cent from Sumitomo Chemical, making NMP a wholly owned subsidiary and giving GE HealthCare direct control of the Japanese radiopharmaceutical channel. In September 2025 Lantheus and GE HealthCare announced an exclusive licence for PYLARIFY (piflufolastat F-18) in Japan, which is how a US PSMA tracer reaches the Japanese market.","asOf":"2026-09-22","links":[{"label":"Company overview (incorporated 20 March 1973; shareholder GE HealthCare)","url":"https://www.nmp.co.jp/eng/profile/about.html"},{"label":"GE HealthCare completes acquisition of Nihon Medi-Physics","url":"https://www.gehealthcare.com/en-us/about/newsroom/press-releases/ge-healthcare-completes-acquisition-of-nihon-medi-physics-nmp-a-leading-radiopharmaceutical-company-in-japan"},{"label":"PMDA list of approved drugs (April 2004 onwards)","url":"https://www.pmda.go.jp/files/000281190.pdf"}],"tags":[],"related":["ge-healthcare","i-123-ioflupane","f-18-flutemetamol","fluciclovine-f18","pylarify","jsnm","pmda","f-18","i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Tokyo, Japan","country":"JP","companyType":"radiopharma","website":"https://www.nmp.co.jp/eng/","founded":1973,"stage":"acquired","investors":[],"funding":[],"acquiredBy":"ge-healthcare","route":"/companies/nihon-medi-physics/"}
{"id":"pdradiopharma","kind":"company","name":"PDRadiopharma","aka":["PDRadiopharma Inc.","PDR"],"tldr":"The Japanese radiopharmaceutical business that PeptiDream bought from FUJIFILM: it sells most of Japan's radioactive diagnostics and the therapies that go with them.","summary":"PDRadiopharma is a wholly owned subsidiary of PeptiDream, listed on its own company outline as \"PeptiDream Inc. 100%\". The legal entity started business on 28 March 2022, when the radiopharmaceutical business of FUJIFILM Toyama Chemical transferred to it, but the operation traces back to 1968 - which is why PDRadiopharma holds Japanese approvals granted long before the company existed.\n\nPeptiDream states the subsidiary commercialises 24 diagnostic and 8 therapeutic products in Japan. Its product pages list sodium pertechnetate generators, iodine-123 brain perfusion agents and sodium iodide I-131 therapy capsules; the PMDA's English approval list adds Lutathera and LysaKare (June 2021, originally approved to FUJIFILM Toyama Chemical), Amyvid, MyoMIBG-I123, Tauvid (December 2024) and Raiatt MIBG-I 131 (September 2025). That makes it the counterpart in Japan to Curium or Lantheus in the West: the domestic supplier of the routine agents on which the therapy business rests.","asOf":"2026-09-22","links":[{"label":"Company outline (shareholder PeptiDream Inc. 100%, business start 28 March 2022)","url":"https://www.pdradiopharma.com/en/about/outline/"},{"label":"PeptiDream company profile (radiopharmaceutical business through PDRadiopharma)","url":"https://www.peptidream.com/en/company/profile/"},{"label":"Diagnostic product list","url":"https://www.pdradiopharma.com/en/hcw/products/diagnostic/"},{"label":"Therapeutic product list","url":"https://www.pdradiopharma.com/en/hcw/products/therapeutic/"}],"tags":[],"related":["lutathera","f-18-flortaucipir","f-18-florbetapir","i-123-mibg-cardiac","radioactive-iodine","jsnm","pmda","i-123","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Tokyo, Japan","country":"JP","companyType":"radiopharma","website":"https://www.pdradiopharma.com/en/","founded":2022,"stage":"private-large","investors":[],"funding":[],"route":"/companies/pdradiopharma/"}
{"id":"china-isotope-radiation","kind":"company","name":"China Isotope & Radiation Corporation","aka":["CIRC","China Isotope and Radiation Corporation"],"tldr":"China's state-backed isotope and nuclear medicine group: it makes the radioactive material and the medicines that use it.","summary":"CIRC describes itself in its 2025 annual report as \"a leading enterprise in isotope and irradiation application in China\", founded in 1983 and listed on the Hong Kong Stock Exchange main board on 6 July 2018 under stock code 1763. It is a controlling subsidiary of China National Nuclear Corporation (CNNC), the state nuclear group; in August 2025 a 33.79 per cent block held by China Baoyuan was transferred to CNNC without consideration, concentrating state control further. Revenue for 2025 was RMB 7,187.7 million, down 5.1 per cent year on year.\n\nIts business spans the chain rather than one product: nuclides, nuclear medicines, nuclear-medicine departments and equipment, irradiation services and radiation sources. The 2025 report records the launch of terbium-161 with exclusive agency rights - an isotope still experimental in the West - and its subsidiary HTA (id: hta-atom-hi-tech) achieved domestic large-scale germanium-68 production in February 2026. For Nuclide the group matters as the supply-side answer to why Chinese radioligand programmes can scale without Western isotope imports.","asOf":"2026-09-22","links":[{"label":"CIRC 2025 annual report (HKEXnews): founding 1983, stock code 1763, CNNC control","url":"https://www.hkexnews.hk/listedco/listconews/sehk/2026/0422/2026042200023.pdf"},{"label":"CIRC 2025 annual results announcement (revenue RMB 7,187.7 million; terbium-161 agency)","url":"https://www.hkexnews.hk/listedco/listconews/sehk/2026/0327/2026032704522.pdf"}],"tags":[],"related":["hta-atom-hi-tech","tb-161","ge-68","mo-99","csnm"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Beijing, China","country":"CN","companyType":"radiopharma","website":"https://www.circ.com.cn/","ticker":"HKEX: 1763","founded":1983,"stage":"public","investors":[],"funding":[],"route":"/companies/china-isotope-radiation/"}
{"id":"hta-atom-hi-tech","kind":"company","name":"HTA (Atom Hi-Tech)","aka":["HTA Co., Ltd.","Atom Hi-Tech","Atom High-Tech"],"tldr":"The Chinese state group's radiopharmaceutical arm, and the first company to make germanium-68 generators' feedstock at scale in China.","summary":"HTA is the radiopharmaceutical subsidiary of China Isotope & Radiation Corporation (id: china-isotope-radiation), and so sits under CNNC. In February 2026 CNNC announced that HTA had achieved domestic large-scale production of germanium-68 on a 30 MeV proton cyclotron - the parent isotope of the gallium-68 generators used for PSMA and DOTATATE PET - with each batch exceeding 3.7 GBq and nuclear purity above 99.9 per cent, described as China's first independent, stable, large-scale Ge-68 capability.\n\nThat is the supply story; the product story is that HTA also holds Chinese approvals for routine agents including therapeutic sodium iodide I-131 capsules, and runs lutetium-177 and gallium-68 somatostatin-receptor programmes. Together with the Qinshan reactor route for lutetium-177, it is why China's domestic radioligand pipeline is less exposed to European isotope supply than most.","asOf":"2026-09-22","links":[{"label":"CNNC: China achieves large-scale production of Germanium-68 (HTA, February 2026)","url":"https://en.cnnc.com.cn/2026-02/13/c_1164555.htm"},{"label":"CIRC 2025 annual report (HTA listed as a subsidiary)","url":"https://www.hkexnews.hk/listedco/listconews/sehk/2026/0422/2026042200023.pdf"}],"tags":[],"related":["china-isotope-radiation","ge-68","ga-68","lu-177","radionuclide-generators-kits","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Beijing, China","country":"CN","companyType":"radiopharma","website":"https://www.atom-hitech.com/","stage":"public","investors":[],"funding":[],"route":"/companies/hta-atom-hi-tech/"}
{"id":"cellbion","kind":"company","name":"CellBion","aka":["CellBion Co., Ltd.","Cellbion"],"tldr":"A Korean company developing a lutetium-177 prostate cancer therapy of its own, now filed for conditional approval in Korea.","summary":"CellBion was founded in July 2010 and is based at Daehak-ro, Jongno-gu, Seoul, on the Seoul National University cancer laboratory site; it is listed on KOSDAQ under code 308430. Its own description of the business is \"the advancement of Radioligand Therapy (RLT) and Antibody Radionuclide Conjugates (ARC)\".\n\nThe lead asset is lutetium-177 DGUL (pocuvotide) for metastatic castration-resistant prostate cancer, with the matching gallium-68 NGUL diagnostic. The company's pipeline page states that \"conditional approval is anticipated shortly following the completion of Phase 2 trials in Korea\", and Korean trade press reported in 2026 that the conditional-approval application had been submitted to the MFDS. Behind it sit an actinium-225 DGUL programme and an actinium-225 antibody conjugate, both preclinical, and a phase 1 combination of the lutetium agent with pembrolizumab. If approved, it would be Korea's first domestically developed radioligand therapy.","asOf":"2026-09-22","links":[{"label":"CellBion company profile (founded July 2010, Seoul)","url":"http://cellbion.co.kr/?r=reen&c=98/105"},{"label":"CellBion pipeline (177Lu-DGUL, 68Ga-NGUL, 225Ac programmes)","url":"http://cellbion.co.kr/?r=reen&c=99/108"}],"tags":[],"related":["lu-177","ac-225","prostate-mcrpc","psma-pet","ksnm","kirams","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Seoul, South Korea","country":"KR","companyType":"radiopharma","website":"http://cellbion.co.kr/","ticker":"KOSDAQ: 308430","founded":2010,"stage":"public","investors":[],"funding":[],"route":"/companies/cellbion/"}
{"id":"duchembio","kind":"company","name":"DuChemBio","aka":["DuchemBio Co., Ltd.","DCB"],"tldr":"Korea's biggest maker of diagnostic PET tracers, now building the country's first plant for radioactive cancer therapies.","summary":"DuChemBio makes the routine diagnostic tracers Korean hospitals run on: fluorodeoxyglucose F-18, FP-CIT for Parkinsonian syndromes, and the amyloid PET agents it manufactures under licence for foreign owners, including Neuraceq for Life Molecular Imaging. It was established in November 2002 (as Medicboss) and renamed in December 2007, listed on KONEX in 2014 under code 176750, and moved to KOSDAQ after receiving preliminary approval in November 2024.\n\nIts second business is contract manufacturing, and that is where the therapy side enters: it signed an exclusive licensing and development agreement with Germany's ITM for the lutetium-177 edotreotide therapy in South Korea. In September 2026 it signed a KRW 34.3 billion investment agreement with North Jeolla Province and Jeongeup City to build what Korean reporting describes as the country's first radiopharmaceutical therapy CDMO plant, with commercial production targeted for the second half of 2029. The company's own drug pipeline is diagnostic; the therapy exposure is manufacturing and licences.","asOf":"2026-09-22","links":[{"label":"DuChemBio company history (established 2002, renamed 2007; archived company site)","url":"https://web.archive.org/web/20220115151814/http://duchembio.com/1-3history"},{"label":"ITM and DCB exclusive licensing and development agreement (n.c.a. 177Lu-edotreotide in South Korea)","url":"https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-and-dcb-sign-exclusive-licensing-development-agreement-for-solucin-in-south-korea"},{"label":"DuChemBio to build a KRW 34.3 billion radiopharmaceutical CDMO plant (September 2026)","url":"https://pharmasource.global/content/news/cdmo-news/duchembio-to-build-25-5m-radiopharmaceutical-cdmo-plant-in-south-korea/"}],"tags":[],"related":["fludeoxyglucose-f18","i-123-ioflupane","itm","life-molecular-imaging","ksnm","f-18","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Seoul, South Korea","country":"KR","companyType":"radiopharma","website":"https://www.duchembio.com/","ticker":"KOSDAQ: 176750","founded":2002,"stage":"public","investors":[],"funding":[],"route":"/companies/duchembio/"}
{"id":"annals-of-nuclear-medicine","kind":"journal","name":"Annals of Nuclear Medicine","aka":["Ann Nucl Med"],"tldr":"The English-language journal of Japan's nuclear medicine society.","summary":"Annals of Nuclear Medicine is the official English-language journal of the Japanese Society of Nuclear Medicine (id: jsnm), published by Springer, with print ISSN 0914-7187 and electronic ISSN 1864-6433. It is the main route by which Japanese nuclear medicine work - tracer development, dosimetry, clinical PET and SPECT series - reaches an international readership, and the reason Japanese practice is visible in English even though the society's other journal, Kaku Igaku, is Japanese-language only.\n\nFor this corpus it is a monitored feed rather than a congress source: the society does not deposit meeting abstracts with DOIs, so scripts/fetch-pulse.ts reads the journal's recent articles from Crossref by ISSN (no usable RSS feed exists), and the congress harvest leaves it alone.","asOf":"2026-09-22","links":[{"label":"Annals of Nuclear Medicine (Springer): ISSN 0914-7187 print, 1864-6433 electronic","url":"https://link.springer.com/journal/12149"},{"label":"JSNM publications","url":"https://jsnm.org/english/publications/"}],"tags":[],"related":["jsnm","journal-of-nuclear-medicine","ejnmmi"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Springer (for the Japanese Society of Nuclear Medicine)","url":"https://link.springer.com/journal/12149","issn":"0914-7187","scope":"Nuclear medicine and molecular imaging","access":"hybrid","matchNames":["Annals of Nuclear Medicine","Ann Nucl Med"],"society":"Japanese Society of Nuclear Medicine","route":"/journals/annals-of-nuclear-medicine/"}
{"id":"nuclear-medicine-and-molecular-imaging","kind":"journal","name":"Nuclear Medicine and Molecular Imaging","aka":["Nucl Med Mol Imaging"],"tldr":"The English-language journal of Korea's nuclear medicine society.","summary":"Nuclear Medicine and Molecular Imaging is the official journal of the Korean Society of Nuclear Medicine (id: ksnm), published by Springer with print ISSN 1869-3474 and electronic ISSN 1869-3482. It carries Korean clinical and radiochemistry work in English, which matters here because Korea's radioligand programmes - FutureChem's florastamin and ludotadipep, CellBion's lutetium-177 DGUL - publish domestically well before they appear at Western congresses.\n\nLike its Japanese counterpart it deposits no meeting abstracts, so Nuclide reads it as a literature feed from Crossref by ISSN rather than as a congress source.","asOf":"2026-09-22","links":[{"label":"Nuclear Medicine and Molecular Imaging (Springer): ISSN 1869-3474 print, 1869-3482 electronic","url":"https://link.springer.com/journal/13139"},{"label":"KSNM publication archive","url":"https://www.ksnm.or.kr/eng/pub/search.php"}],"tags":[],"related":["ksnm","cellbion","futurechem","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Springer (for the Korean Society of Nuclear Medicine)","url":"https://link.springer.com/journal/13139","issn":"1869-3474","scope":"Nuclear medicine and molecular imaging","access":"hybrid","matchNames":["Nuclear Medicine and Molecular Imaging","Nucl Med Mol Imaging"],"society":"Korean Society of Nuclear Medicine","route":"/journals/nuclear-medicine-and-molecular-imaging/"}
{"id":"chinese-journal-of-nuclear-medicine-and-molecular-imaging","kind":"journal","name":"Chinese Journal of Nuclear Medicine and Molecular Imaging","aka":["CJNMMI","Zhonghua he yi xue yu fen zi ying xiang za zhi"],"tldr":"China's main nuclear medicine journal. It publishes in Chinese, which is why most of its content is invisible to the usual English-language trackers.","summary":"The Chinese Journal of Nuclear Medicine and Molecular Imaging is sponsored by the Chinese Medical Association and edited by the Jiangsu Institute of Nuclear Medicine, carrying ISSN 2095-2848 and CN 32-1828/R. It was founded in 1981 under an earlier name and has published monthly since 2017. The journal title above is the official English title the publisher itself uses; the journal's contents are in Chinese.\n\nIt is recorded here as a deliberate coverage gap rather than a feed. The journal is not indexed in Crossref (checked 22 September 2026), and a Europe PMC search by journal name returns nothing, so its articles cannot be harvested the way Western journals are. Chinese radiopharmaceutical output is instead tracked through Europe PMC affiliation counts, which returned 6,914 papers with a Chinese affiliation in the year to 22 September 2026, and through worldwide patent filings, where Chinese applicants dominate recent radiopharmaceutical publications.","asOf":"2026-09-22","links":[{"label":"Journal home and masthead (ISSN 2095-2848, CN 32-1828/R)","url":"http://www.zhhyx.com.cn/about.jhtml"},{"label":"Chinese Society of Nuclear Medicine: journal contents","url":"https://chinanm.cma.org.cn/art/2026/4/22/art_1509_60533.html"}],"tags":[],"related":["csnm","china-isotope-radiation"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Chinese Medical Association (edited by the Jiangsu Institute of Nuclear Medicine)","url":"http://www.zhhyx.com.cn/","issn":"2095-2848","scope":"Nuclear medicine and molecular imaging, published in Chinese","access":"subscription","founded":1981,"matchNames":["Chinese Journal of Nuclear Medicine and Molecular Imaging","Zhonghua he yi xue yu fen zi ying xiang za zhi"],"society":"Chinese Society of Nuclear Medicine","route":"/journals/chinese-journal-of-nuclear-medicine-and-molecular-imaging/"}
{"id":"pexiretide-tc99m","kind":"drug","name":"Technetium (99mTc) pexiretide","aka":["99mTc-3PRGD2","technetium [99mTc] pexiretide injection","Jilunte","3PRGD2","锝[99mTc]佩昔瑞特加肽注射液"],"tldr":"A Chinese-invented injection that makes tumours visible on the cheap, widely available type of scanner (SPECT) rather than the expensive one (PET). It was approved in China in April 2026 to check whether lung cancer has spread to the lymph nodes.","summary":"Pexiretide is a dimeric RGD peptide carrying three PEG spacers, labelled with technetium-99m, that targets integrin αvβ3 — a receptor expressed on new tumour blood vessels and on many tumour cells. It was developed by Professor Wang Fan's group at Peking University's Medical Isotope Research Centre on National Natural Science Foundation grants, and China's NMPA approved it on 2 April 2026 under the trade name Jilunte, for SPECT/CT assessment of regional lymph-node metastasis in patients with suspected lung cancer.\n\nThe funder's own announcement calls it the first Class 1 innovative radiopharmaceutical developed independently in China and the world's first broad-spectrum tumour imaging agent for SPECT — a claim about the modality, not the molecule: PET agents dominate general tumour imaging, while SPECT has been confined to bone, thyroid and perfusion work for decades. That distinction is the commercial point. China's installed base of SPECT/CT scanners is roughly two to three times its PET/CT base (Securities Times, citing industry estimates), and a SPECT scan costs a fraction of a PET scan, so a broad tumour agent that runs on the cheaper machine reaches district hospitals that will never own a cyclotron.\n\nThe registrational claim reported in Chinese coverage is that in phase 3 there was no statistically significant difference from 18F-FDG PET/CT in telling benign from malignant lung lesions, while for lung cancer lymph-node metastasis the specificity and accuracy of 99mTc-3PRGD2 SPECT/CT were significantly higher than PET/CT's. The trial report itself is not public in English; the closest peer-reviewed evidence is a prospective head-to-head study in 26 patients with primary malignant lung tumours (Korean Journal of Radiology, 2023), which compared the two scans across 42 metastatic and 136 benign lymph-node stations with histopathology as the reference.\n\nCommercially the agent sits with Ridio (Foshan), a company founded in 2012 out of the Peking University group, whose controlling shareholder is Beijing Jilunte Pharmaceutical; Baiyang Pharmaceutical invested in 2022 and holds the mainland commercialisation rights. An earlier filing was withdrawn in February 2025 and resubmitted before this approval.","status":"approved","asOf":"2026-09-22","links":[{"label":"National Natural Science Foundation of China: the world's first integrin-targeted innovative radiopharmaceutical approved, 2 April 2026 (Chinese)","url":"https://www.nsfc.gov.cn/p1/3381/2825/121910.html"},{"label":"Securities Times: approval, phase 3 comparison with FDG PET/CT and the SPECT installed base (Chinese)","url":"https://stcn.com/article/detail/3725436.html"},{"label":"99mTc-3PRGD2 SPECT/CT for diagnosing lymph node metastasis of primary malignant lung tumours (Korean Journal of Radiology, 2023)","url":"https://doi.org/10.3348/kjr.2023.0411"},{"label":"Advances in clinical oncology research on 99mTc-3PRGD2 SPECT imaging (Frontiers in Oncology, 2022)","url":"https://doi.org/10.3389/fonc.2022.898764"}],"tags":["diagnostic","china","spect","integrin"],"related":["integrin-avb3","tc-99m","spect","csnm","china-isotope-radiation","chinese-journal-of-nuclear-medicine-and-molecular-imaging","f-18"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Jilunte","code":"99mTc-3PRGD2","modality":"Integrin αvβ3-targeted SPECT imaging agent (RGD peptide dimer)","mechanism":"A technetium-99m-labelled dimeric RGD peptide with three polyethylene glycol spacers that binds integrin αvβ3 on tumour neovasculature and tumour cells, so an ordinary SPECT/CT camera can image the lesion.","approvals":[{"region":"China","year":2026,"indication":"SPECT/CT assessment of regional lymph-node metastasis in patients with suspected lung cancer","note":"NMPA approval 2 April 2026; described by its funder as China's first independently developed Class 1 innovative radiopharmaceutical"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2026-04-02","type":"approval","region":"China","note":"NMPA marketing approval (priority review), trade name Jilunte","source":"https://www.nsfc.gov.cn/p1/3381/2825/121910.html"},{"date":"2025-02","type":"withdrawal","region":"China","note":"An earlier new drug application for the same product was withdrawn before being resubmitted; reported by Chinese trade press, not by the regulator","source":"https://www.163.com/dy/article/K0V13Q6H05118K9D.html"}],"route":"/drugs/pexiretide-tc99m/"}
{"id":"nsclc","kind":"indication","name":"Non-small cell lung cancer","aka":["NSCLC","lung cancer","lung adenocarcinoma","lung squamous cell carcinoma","large cell lung carcinoma"],"tldr":"The cancer that kills more people than any other, and the reason most PET scanners are busy. Most cases are found once the disease has already spread, and a scan with radioactive sugar is what decides who can still be cured by surgery.","summary":"Non-small cell lung cancer is the group of lung carcinomas that are not small-cell: adenocarcinoma (about 40% of all lung cancers), squamous cell carcinoma (about 25%) and large cell carcinoma (about 10%), classified by the World Health Organization together with the International Association for the Study of Lung Cancer, with adenosquamous, sarcomatoid and salivary gland-type tumours making up the remainder. Squamous tumours usually start near a central bronchus, adenocarcinomas peripherally. Smoking is the dominant cause: on average a smoker's risk is tenfold that of a lifetime non-smoker, and radon, asbestos, air pollution, prior radiation, family history and HIV infection add to it. Subsets of adenocarcinoma carry targetable alterations in EGFR, ALK, ROS1, BRAF, RET, NTRK1-3, MET, KRAS and HER2; EGFR and ALK predominate in never-smokers while KRAS and BRAF are commoner in current and former smokers, so molecular typing and PD-L1 scoring now precede treatment in metastatic disease.\n\nNuclear medicine's role here is diagnostic and it is decisive. The staging work-up runs from history, examination and contrast-enhanced chest CT to 18F-FDG PET, with tissue taken by bronchoscopy, mediastinoscopy or anterior mediastinotomy. Across 44 studies and 2,865 patients, FDG PET detected mediastinal nodal metastasis with a pooled sensitivity of 74% (95% CI 69-79) and specificity of 85% (95% CI 82-88), against roughly 61% and 79% for CT, and a randomised trial found that adding FDG PET to conventional staging significantly reduced the number of thoracotomies. It does not replace sampling: because false positives are frequent enough that forgoing mediastinoscopy on a PET-positive node was judged unsafe, a positive mediastinum is still biopsied, while PET's main practical value is finding the distant deposit that makes surgery futile. Since 1 January 2025 the reporting task has changed shape: the ninth edition of TNM splits N2 into N2a (single-station) and N2b (multiple-station) and M1c into M1c1 (several metastases in one organ system) and M1c2 (several organ systems), so a scan report now has to count nodal stations and organ systems rather than simply call the mediastinum positive.\n\nWhat is moving. China approved technetium (99mTc) pexiretide in April 2026, an integrin alpha-v-beta-3 RGD peptide that puts the same staging question on a SPECT/CT scanner, which matters where SPECT capacity far exceeds PET capacity. 68Ga-FAPI-04, which targets the fibroblast scaffolding rather than glucose metabolism, detected primary NSCLC with 96.7% sensitivity and staged nodal stations at 72.0% sensitivity and 93.1% specificity in a 91-patient series, the specificity FDG lacks. Research tracers including 18F-FLT for proliferation and 18F-F-AraG for T-cell activity are in trials aimed at response rather than extent. Therapy is the gap: no radiopharmaceutical is approved to treat lung cancer of any histology anywhere, and the alpha-emitting DLL3 programmes now in the clinic are aimed at small-cell disease, which has its own record.","asOf":"2026-09-22","wikipedia":"https://en.wikipedia.org/wiki/Non-small-cell_lung_cancer","links":[{"label":"NCI PDQ: non-small cell lung cancer treatment (health professional)","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"},{"label":"SEER Cancer Stat Facts: lung and bronchus cancer","url":"https://seer.cancer.gov/statfacts/html/lungb.html"},{"label":"IARC Global Cancer Observatory: trachea, bronchus and lung factsheet (GLOBOCAN 2024)","url":"https://gco.iarc.fr/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf"},{"label":"NCCN Guidelines: Non-Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"},{"label":"USPSTF: lung cancer screening, final recommendation statement (2021)","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening"},{"label":"Implementation of the 9th TNM for lung cancer: practical points (2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12165876/"},{"label":"18F-FLT and 18F-FDG uptake versus Ki-67 in NSCLC (Eur J Nucl Med Mol Imaging, 2007)","url":"https://doi.org/10.1007/s00259-007-0449-7"},{"label":"68Ga-FAPI-04 PET/CT in NSCLC: nodal metastasis and FAP expression (J Nucl Med, 2024)","url":"https://doi.org/10.2967/jnumed.123.266806"}],"tags":["lung","diagnostic","staging"],"related":["sclc","lung-net","f-18","tc-99m","ga-68","pb-212-psv359","pulmonary-embolism-vq","split-function-lung-perfusion"],"indications":["sclc","lung-net"],"sections":[],"technologies":["fdg-pet","pet-ct","ct","spect-ct","fapi-pet","radiomics","split-function-lung-perfusion"],"targets":["glut-hexokinase","fap","integrin-avb3"],"drugs":["fludeoxyglucose-f18","pexiretide-tc99m","ga-68-fapi-46","f-18-fluorothymidine","tc-99m-mdp","tc-99m-maa"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06107374","nct07276789"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"lung","burden":"Lung cancer ranks first worldwide in both incidence and mortality: GLOBOCAN 2024 estimates 2,637,005 new cases (age-standardised rate 23.9 per 100,000) and 1,861,839 deaths (16.3 per 100,000) a year. The NCI estimated 226,650 new US cases and 124,730 deaths for 2025, small-cell and non-small-cell combined, making it the leading cause of cancer death in the United States. Non-small-cell histologies are the large majority of that total.","subtypes":["Adenocarcinoma (about 40% of all lung cancers; usually peripheral)","Squamous cell carcinoma (about 25%; usually near a central bronchus)","Large cell carcinoma (about 10%)","Adenosquamous carcinoma","Sarcomatoid carcinoma","Salivary gland-type tumours of the lung"],"biomarkers":["EGFR","ALK","ROS1","BRAF","RET","NTRK1, NTRK2, NTRK3","MET","KRAS","HER2","PD-L1 tumour proportion score (22C3 immunohistochemistry)","Stage (ninth-edition TNM) remains the dominant treatment determinant"],"standardOfCare":[{"setting":"Screening in people at risk","approach":"Annual low-dose CT for adults aged 50 to 80 with a 20 pack-year smoking history who still smoke or quit within the past 15 years; stopped after 15 smoke-free years or when a competing health problem limits benefit.","refs":["ct"],"guideline":{"version":"USPSTF final recommendation statement, 9 March 2021","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening"}},{"setting":"Diagnosis and initial staging","approach":"History, examination, laboratory tests, chest radiograph and contrast-enhanced chest CT, then 18F-FDG PET; tissue obtained by bronchoscopy, mediastinoscopy or anterior mediastinotomy.","refs":["ct","fdg-pet","pet-ct","fludeoxyglucose-f18"],"guideline":{"version":"NCCN Guidelines: Non-Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"}},{"setting":"Mediastinal nodes positive on PET","approach":"Pathological confirmation before a curative-intent plan is abandoned, because the false-positive rate makes PET alone an unsafe basis for withholding surgery.","refs":["fdg-pet","pet-ct"],"guideline":{"version":"NCCN Guidelines: Non-Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"}},{"setting":"Suspected distant spread","approach":"Bone scintigraphy and CT or MRI of the brain when symptoms, signs, laboratory findings or perceived risk suggest metastatic disease that PET may not resolve.","refs":["tc-99m-mdp","ct"],"guideline":{"version":"NCI PDQ, NSCLC treatment (health professional)","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"}},{"setting":"Resectable early-stage disease","approach":"Surgery with mediastinal nodal evaluation, with adjuvant systemic therapy for larger or node-positive tumours; stereotactic body radiotherapy or conventional radiotherapy where the patient is inoperable.","refs":[],"guideline":{"version":"NCCN Guidelines: Non-Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"}},{"setting":"Locally advanced unresectable disease","approach":"Radiotherapy combined with chemotherapy, with long-term survival achievable in a minority.","refs":[],"guideline":{"version":"NCI PDQ, NSCLC treatment (health professional)","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"}},{"setting":"Advanced metastatic disease","approach":"Systemic therapy directed by molecular typing and PD-L1 score: targeted agents where a driver alteration is present, chemotherapy and immunotherapy otherwise, alongside supportive care.","refs":[],"guideline":{"version":"NCCN Guidelines: Non-Small Cell Lung Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"}}],"stateOfArt":["18F-FDG PET/CT is the staging backbone. Pooled across 44 studies and 2,865 patients, sensitivity for mediastinal nodal metastasis was 74% (95% CI 69-79) and specificity 85% (95% CI 82-88), against about 61% and 79% for CT; the median prevalence of mediastinal metastases in those series was 29%.","PET changes management mainly by finding disease outside the chest. A randomised study found significantly fewer thoracotomies when FDG PET was added to conventional staging, but the trials disagree on how many futile operations it prevents, and PET-positive mediastinal nodes still require sampling.","The ninth edition of TNM, effective 1 January 2025, leaves the T categories unchanged but divides N2 into N2a (single-station) and N2b (multiple-station) and M1c into M1c1 (multiple metastases in one organ system) and M1c2 (metastases in multiple organ systems), which moves some patients to a lower stage group and puts the burden of counting stations and organ systems onto the imaging report.","Technetium (99mTc) pexiretide, approved by China's NMPA on 2 April 2026, is the first approved alternative that answers the nodal-staging question on SPECT/CT rather than PET/CT, a distinction that matters in health systems whose SPECT installed base is several times their PET capacity.","68Ga-FAPI-04 PET/CT detected the primary tumour with 96.7% sensitivity and 100% positive predictive value, and staged nodal stations with 72.0% sensitivity, 93.1% specificity and 89.4% accuracy, in 91 patients with NSCLC; uptake correlated with fibroblast activation protein expression in resected specimens.","No radiopharmaceutical therapy is approved for lung cancer of any histology. Targets identified in lung tumours (fibroblast activation protein, integrin alpha-v-beta-3) are so far used for imaging only, and the alpha-emitting DLL3 programmes in the clinic are directed at small-cell disease."],"history":[{"year":2010,"title":"Revised international staging system adopted by AJCC and UICC","note":"Built from a clinical database of more than 5,000 patients; gave greater prognostic specificity to the stage groups.","refs":[]},{"year":2021,"title":"USPSTF widens low-dose CT screening","note":"Final statement of 9 March 2021: annual LDCT for adults aged 50 to 80 with a 20 pack-year history who smoke or quit within 15 years, lowering both the age and pack-year thresholds.","refs":[]},{"year":2025,"title":"Ninth-edition TNM takes effect on 1 January","note":"N2 splits into N2a and N2b, M1c into M1c1 and M1c2; T categories unchanged.","refs":["pet-ct"]},{"year":2026,"title":"China approves technetium (99mTc) pexiretide for nodal staging","note":"NMPA approval on 2 April 2026 of an integrin alpha-v-beta-3 RGD peptide for SPECT/CT assessment of regional lymph nodes in suspected lung cancer.","refs":["pexiretide-tc99m"]}],"pipeline":["pexiretide-tc99m","ga-68-fapi-46","fapi-pet","f-18-fluorothymidine","pb-212-psv359","nct06107374","nct07276789"],"openProblems":["FDG PET misses about a quarter of mediastinal nodal metastases, so a negative mediastinum on PET does not reliably spare a patient invasive staging when the pre-test probability is high.","False positives are frequent enough that a PET-positive mediastinal node cannot be treated as proof of spread; the money saved by skipping mediastinoscopy was judged not to justify the error rate.","Glucose metabolism is a non-specific target. FAP and integrin imaging offer higher specificity for nodal disease but neither has a regulatory approval outside China, and neither has been tested head-to-head against FDG in a registrational trial.","There is no theranostic pair in lung cancer: every approved agent here is diagnostic, and no radioligand therapy has reached approval in any lung histology.","The ninth-edition N2a/N2b and M1c1/M1c2 subdivisions require station-level and organ-system-level reporting that most existing structured-report templates and PET reporting software do not yet produce.","Most of the world's 2.6 million annual cases arise where PET capacity is thinnest, which is the practical argument for the SPECT-based alternative China approved rather than for a better PET tracer."],"basics":{"symptoms":["Worsening cough, chest pain, haemoptysis, malaise, weight loss, breathlessness and hoarseness are the commonest presenting complaints.","Many tumours are found incidentally on chest imaging performed for another reason.","Symptoms may come from local invasion or compression of adjacent structures, for example dysphagia from oesophageal compression or hoarseness from laryngeal nerve involvement."],"diagnosis":["Tissue is obtained by bronchoscopy, mediastinoscopy or anterior mediastinotomy; histology is classified under the WHO/IASLC system.","Imaging work-up is contrast-enhanced chest CT followed by 18F-FDG PET, with bone scintigraphy and brain CT or MRI when distant spread is suspected.","Molecular testing for EGFR, ALK, ROS1, BRAF, RET, NTRK, MET, KRAS and HER2, plus PD-L1 immunohistochemistry, directs systemic treatment in advanced disease."],"staging":["The ninth edition of TNM has applied since 1 January 2025.","N2 is now split into N2a (single nodal station) and N2b (multiple stations); M1c is split into M1c1 (multiple metastases in a single organ system) and M1c2 (metastases in multiple organ systems). The T categories are unchanged from the eighth edition.","Pathological staging requires examination of the tumour, knowledge of the resection margins and determination of nodal status; clinical and pathological stage can differ."],"sources":[{"label":"NCI PDQ: non-small cell lung cancer treatment (health professional)","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"},{"label":"Implementation of the 9th TNM for lung cancer: practical points (2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12165876/"}]},"prognosis":{"text":"Five-year relative survival for lung and bronchus cancer is 29.5% in SEER 21 (excluding Illinois) for 2016-2022, and stage at diagnosis dominates it: 24% of cases are localised with 65.5% survival, 21% regional with 38.2%, and 51% distant with 10.5%; 4% are unstaged at 17.5%. US incidence is 47.2 and mortality 30.2 per 100,000 per year. Because half of all patients are already metastatic when they are diagnosed, the population figure is pulled far below what any individual early-stage patient should expect, and the numbers pool small-cell with non-small-cell disease.","sources":[{"label":"SEER Cancer Stat Facts: lung and bronchus cancer","url":"https://seer.cancer.gov/statfacts/html/lungb.html"}]},"route":"/indications/nsclc/"}
{"id":"colorectal-cancer","kind":"indication","name":"Colorectal cancer","aka":["bowel cancer","colon cancer","rectal cancer","CRC"],"tldr":"The third commonest cancer in the world and the second biggest cancer killer. Most of it is curable if caught before it spreads, which is why so much of the imaging effort goes into finding out whether it has.","summary":"Colorectal cancer is an adenocarcinoma of the colon or rectum, usually arising from an adenomatous polyp over years. GLOBOCAN 2024 puts it third for incidence worldwide with 2,041,007 new cases and second for mortality with 917,895 deaths. In the United States, SEER projects 158,850 new cases and 55,230 deaths for 2026, with five-year relative survival of 65.4% overall but 91.3% for localised disease against 16.9% once it has spread to distant sites, and 23% of cases are already distant at diagnosis. That gradient is why every part of the pathway is organised around finding disease early and finding it completely.\n\nTreatment splits by site and stage. Localised colon cancer is resected, with adjuvant oxaliplatin-based chemotherapy for stage III. Locally advanced rectal cancer has moved to total neoadjuvant therapy, giving all chemotherapy and chemoradiation before surgery, which the NCI's summary calls the preferred approach and which allows some patients with a complete clinical response to avoid surgery altogether under intensive surveillance. Metastatic disease is treated by biomarker: anti-EGFR antibodies only in RAS wild-type tumours, encorafenib with cetuximab for the roughly 10% with BRAF V600E, and pembrolizumab first line for the roughly 4% of stage IV disease that is mismatch-repair deficient, where KEYNOTE-177 gave median progression-free survival of 16.5 against 8.2 months.\n\nNuclear medicine's role here is narrow and specific, and that is the point for radiopharmaceutical development. FDG PET/CT is not indicated for routine staging or routine surveillance. Its accepted niches are equivocal conventional imaging, work-up before resection of potentially curable liver metastases, and the scenario that matters most for tracer development: a serially rising carcinoembryonic antigen with negative conventional imaging, where pooled FDG PET/CT sensitivity and specificity have been reported at 94.1% and 77.2%. The only agent ever approved specifically for occult colorectal recurrence, the anti-CEA antibody fragment arcitumomab, was withdrawn from the market in 2005 and nothing has replaced it.","asOf":"2026-09-23","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"IARC GLOBOCAN 2024 colorectum factsheet","url":"https://gco.iarc.who.int/media/globocan/factsheets/cancers/41-colorectum-fact-sheet.pdf"},{"label":"SEER Cancer Stat Facts: colorectal cancer","url":"https://seer.cancer.gov/statfacts/html/colorect.html"},{"label":"NCI PDQ: colon cancer treatment, health professional version","url":"https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq"},{"label":"NCI PDQ: rectal cancer treatment, health professional version","url":"https://www.cancer.gov/types/colorectal/hp/rectal-treatment-pdq"},{"label":"Review of PET/CT in colorectal cancer, including the rising-CEA indication","url":"https://www.mdpi.com/2072-6694/14/11/2668"},{"label":"DYNAMIC five-year results, Nature Medicine 2025","url":"https://www.nature.com/articles/s41591-025-03579-w"}],"tags":["gastrointestinal","surveillance","recurrence"],"related":["ceacam5","fdg-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"GLOBOCAN 2024 reports 2,041,007 new cases a year worldwide, an age-standardised rate of 18.6 per 100,000, ranking third for incidence, and 917,895 deaths at 7.8 per 100,000, ranking second for cancer mortality. SEER projects 158,850 new US cases and 55,230 US deaths in 2026.","subtypes":["Colon adenocarcinoma","Rectal adenocarcinoma","Mismatch-repair deficient / microsatellite instability-high disease (about 4% of stage IV)","BRAF V600E-mutant disease (about 10% of metastatic cases)","HER2-positive, RAS wild-type disease"],"biomarkers":["RAS (KRAS/NRAS) mutation status, which decides whether anti-EGFR antibodies can be used","BRAF V600E, present in about 10% of metastatic cases and a marker of poor prognosis","Mismatch repair / microsatellite instability, by immunohistochemistry or molecular testing","HER2 amplification, for tucatinib with trastuzumab in RAS wild-type disease","Carcinoembryonic antigen (CEA) in serum, for surveillance rather than diagnosis","Tumour-informed circulating tumour DNA, validated for de-escalating adjuvant chemotherapy"],"standardOfCare":[{"setting":"Localised colon cancer","approach":"Surgical resection of the primary and regional nodes, with adjuvant oxaliplatin-based chemotherapy for stage III; adjuvant radiotherapy has no standard role.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq"}},{"setting":"Locally advanced rectal cancer","approach":"Total neoadjuvant therapy is the preferred approach; patients with a complete clinical response may be managed non-operatively with intensive surveillance instead of resection.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/colorectal/hp/rectal-treatment-pdq"}},{"setting":"Metastatic disease, first line","approach":"Chemotherapy backbone with bevacizumab, plus anti-EGFR antibodies only in RAS wild-type tumours; pembrolizumab alone for mismatch-repair deficient disease.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq"}},{"setting":"Surveillance after curative resection","approach":"CEA every three to six months for the first two years then six-monthly to five years, with contrast CT of chest, abdomen and pelvis; FDG PET/CT is not indicated routinely but is considered when CEA rises and conventional imaging is negative.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq"}}],"stateOfArt":["Organ preservation is now a real option in rectal cancer: after total neoadjuvant therapy, a complete clinical response can be watched rather than operated on, though the optimal surveillance protocol has not been determined and about a quarter of these patients develop local regrowth, mostly within two years.","Circulating tumour DNA has changed adjuvant decision-making in one direction only. The randomised DYNAMIC trial cut adjuvant chemotherapy use from 27.9% to 15.3% in stage II colon cancer while remaining non-inferior at five years, but ctDNA positivity has not yet reliably identified patients who benefit from escalating treatment.","FDG PET/CT is used for the rising-CEA problem rather than for staging, with pooled sensitivity and specificity of 94.1% and 77.2% and sensitivity that rises with the CEA level, from 83.3% at a CEA of 3.4 ng/mL or below to 100% above 30 ng/mL."],"history":[{"year":2020,"title":"FDA approved pembrolizumab first line for mismatch-repair deficient metastatic colorectal cancer","note":"Based on KEYNOTE-177, which gave median progression-free survival of 16.5 against 8.2 months.","refs":[]},{"year":2023,"title":"Tucatinib with trastuzumab given accelerated approval for RAS wild-type, HER2-positive metastatic disease","note":"The first approved targeted regimen for HER2-positive colorectal cancer, on 19 January 2023.","refs":[]},{"year":2025,"title":"Five-year DYNAMIC results confirmed ctDNA-guided de-escalation of adjuvant chemotherapy is non-inferior in stage II colon cancer","note":"Published in Nature Medicine; adjuvant chemotherapy use fell from 27.9% to 15.3%.","refs":[]}],"pipeline":["opp-ceacam5-imaging-colorectal","ceacam5","fdg-pet"],"openProblems":["Nodal staging is unreliable: pooled CT sensitivity and specificity for nodal involvement are about 64 to 71% and 67%, and up to half of metastatic nodes are 5 mm or smaller, so CT-detected nodal involvement should not be relied on alone.","Peritoneal metastases are systematically missed, with a CT detection rate of only 20 to 25% for nodules under 5 mm and underestimation of the surgical peritoneal cancer index by 12 to 33%.","A positive ctDNA result with negative imaging is a management dilemma rather than an answer: nothing localises the disease it has detected, and no molecular imaging agent is approved for that scenario since arcitumomab was withdrawn in 2005.","Watch-and-wait surveillance after rectal organ preservation has no agreed protocol, which makes it hard to know how often and with what modality to look."],"prognosis":{"text":"Survival depends almost entirely on how far the cancer has spread when it is found. SEER reports five-year relative survival of 65.4% overall for patients diagnosed between 2016 and 2022: 91.3% for localised disease, which is 34% of cases, 75.2% for regional disease at 37% of cases, and 16.9% for distant disease at 23% of cases. These are averages across all ages and treatments and say nothing about an individual patient.","sources":[{"label":"SEER Cancer Stat Facts: colorectal cancer","url":"https://seer.cancer.gov/statfacts/html/colorect.html"}]},"route":"/indications/colorectal-cancer/"}
{"id":"urothelial-cancer","kind":"indication","name":"Urothelial cancer","aka":["bladder cancer","transitional cell carcinoma","urothelial carcinoma","UC"],"tldr":"Urothelial cancer mostly starts in the bladder lining and ranges from tumours that stay superficial and are managed for years with local treatments to disease that spreads and needs systemic therapy. Survival depends heavily on how early it is caught, which is why so much attention goes into staging it accurately.","summary":"Urothelial cancer, most commonly bladder cancer, arises from the transitional epithelium lining the urinary tract. GLOBOCAN 2022 estimated 614,298 new cases and 220,596 deaths worldwide, with roughly 75% of the burden occurring in men, while the newer GLOBOCAN 2024 release put incidence at 635,264 cases, ranked eighth worldwide, and mortality at 227,626 deaths, ranked thirteenth. In the United States, SEER projects 84,530 new cases and 17,870 deaths for 2026, with an incidence rate of 17.9 per 100,000 and a death rate of 4.1 per 100,000. Five-year relative survival is 79.1% overall, but this conceals a very wide stage gradient: 98.0% for in situ disease, which makes up half of cases, 73.0% for localised disease, 41.8% for regional disease, and only 9.6% for distant disease.\n\nTreatment is stratified by depth of invasion and risk. Non-muscle-invasive disease is treated with transurethral resection followed by intravesical chemotherapy and, for higher-risk tumours, bacillus Calmette-Guerin; BCG-unresponsive disease now has three FDA-approved options, pembrolizumab, the intravesical gene therapy nadofaragene firadenovec, and radical cystectomy for those fit for surgery. Muscle-invasive disease is treated with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy, or with bladder-sparing trimodal chemoradiation, and since 2025 with perioperative pembrolizumab plus enfortumab vedotin, an approval extended in 2026 to cisplatin-eligible patients based on KEYNOTE-B15/EV-304. Adjuvant nivolumab is standard after cystectomy in patients at high recurrence risk. Metastatic disease is now led by enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, combined with pembrolizumab as first-line therapy regardless of cisplatin eligibility, with erdafitinib reserved for the roughly 20% of patients whose tumours carry an actionable FGFR2/3 alteration.\n\nNuclear medicine's role in staging urothelial cancer remains unsettled and is limited chiefly by physiology. FDG accumulates in urine and is excreted through the collecting system, obscuring the primary tumour and adjacent pelvic nodes on FDG PET/CT, the exact anatomical region that matters most for surgical planning. AUA, EAU, ESMO and NCCN guidelines diverge as a result: the US-oriented consensus is to avoid routine PET in initial staging and consider it only in selected or indeterminate cases, while ESMO and EAU jointly recommend systematic FDG PET/CT staging in oligometastatic patients being considered for radical treatment, to avoid overtreatment. Meta-analysis nodal-staging accuracy is modest across all modalities, with pooled sensitivity of about 0.40 for CT, 0.60 for MRI and 0.56 for FDG PET/CT against specificities around 0.91 to 0.92, leaving occult nodal disease a persistent blind spot before radical cystectomy.","asOf":"2026-09-23","links":[{"label":"IARC GLOBOCAN 2024 bladder factsheet","url":"https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf"},{"label":"SEER Cancer Stat Facts: bladder cancer","url":"https://seer.cancer.gov/statfacts/html/urinb.html"},{"label":"NCI PDQ: bladder cancer treatment, health professional version","url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"},{"label":"FDA approval: enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer"},{"label":"Guideline of guidelines: muscle-invasive bladder cancer, PMC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8057355/"},{"label":"PET imaging in bladder cancer: an update and future direction, MDPI","url":"https://www.mdpi.com/1424-8247/16/4/606"}],"tags":["urological","staging","nodal-staging"],"related":["nectin4","fdg-pet","immuno-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"urological","burden":"GLOBOCAN 2022 estimated 614,298 new cases and 220,596 deaths worldwide, about 75% of them in men. The newer GLOBOCAN 2024 release put incidence at 635,264 cases, ranked eighth worldwide with an age-standardised rate of 5.5 per 100,000, and mortality at 227,626 deaths, ranked thirteenth at 1.8 per 100,000. SEER projects 84,530 new US cases and 17,870 US deaths for 2026, with an incidence rate of 17.9 and a death rate of 4.1 per 100,000.","subtypes":["Non-muscle-invasive bladder cancer (Ta, Tis/carcinoma in situ, T1)","Muscle-invasive bladder cancer","Metastatic urothelial carcinoma","FGFR2/3-altered urothelial carcinoma"],"biomarkers":["FGFR3/FGFR2 genetic alterations, present in about 20% of metastatic urothelial carcinoma and required by an FDA-approved companion diagnostic to qualify patients for erdafitinib","PD-L1 expression, used as a stratification factor in the CheckMate 274 adjuvant nivolumab trial though not required for pembrolizumab use in NMIBC","Urine cytology and cystoscopy with biopsy, used to define complete response in BCG-unresponsive-disease trials"],"standardOfCare":[{"setting":"Non-muscle-invasive disease (Ta/Tis/T1)","approach":"Transurethral resection of the bladder tumour followed by a single immediate instillation of intravesical chemotherapy, typically mitomycin, with periodic intravesical BCG instillations for higher-risk disease based on risk stratification.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"NMIBC, BCG-unresponsive","approach":"Pembrolizumab or intravesical nadofaragene firadenovec gene therapy for patients ineligible for or declining cystectomy, with radical cystectomy remaining the definitive option for those medically fit for it.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"Muscle-invasive disease","approach":"Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy and urinary diversion, or bladder-sparing trimodal chemoradiation; perioperative pembrolizumab with enfortumab vedotin around cystectomy for cisplatin-ineligible and, since 2026, cisplatin-eligible patients; adjuvant nivolumab after cystectomy for those at high recurrence risk.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"Metastatic disease, first line","approach":"Enfortumab vedotin plus pembrolizumab for all patients regardless of cisplatin eligibility; platinum-based chemotherapy where the combination is unavailable; erdafitinib after progression in patients with a susceptible FGFR3 alteration.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}}],"stateOfArt":["Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, combined with pembrolizumab has replaced platinum chemotherapy as first-line therapy for locally advanced or metastatic urothelial cancer, with the EV-302/KEYNOTE-A39 trial reporting median overall survival of 31.5 months against 16.1 months for chemotherapy.","Perioperative use of pembrolizumab with enfortumab vedotin around radical cystectomy was approved in 2025 for cisplatin-ineligible muscle-invasive disease and extended in 2026 to cisplatin-eligible patients, based on KEYNOTE-B15/EV-304, which reported a 47% reduction in the risk of event-free survival events compared with neoadjuvant chemotherapy and surgery.","Guideline bodies disagree on the role of PET in staging: AUA, EAU and NCCN restrict FDG PET/CT to selected or indeterminate cases in initial staging, while ESMO and EAU jointly recommend it specifically for staging oligometastatic patients being considered for radical treatment, reflecting a genuine transatlantic practice discrepancy."],"history":[{"year":2020,"title":"FDA approved pembrolizumab for BCG-unresponsive, high-risk non-muscle-invasive bladder cancer with carcinoma in situ","note":"Approved 8 January 2020 for patients ineligible for or declining cystectomy.","refs":[]},{"year":2021,"title":"Nivolumab approved for adjuvant treatment of high-risk urothelial carcinoma after radical resection","note":"Based on CheckMate 274, median disease-free survival 20.8 versus 10.8 months; approved 19-20 August 2021.","refs":[]},{"year":2022,"title":"Nadofaragene firadenovec-vncg (Adstiladrin) approved","note":"First gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ, approved 16 December 2022.","refs":[]},{"year":2023,"title":"Enfortumab vedotin plus pembrolizumab granted full FDA approval for all locally advanced or metastatic urothelial cancer regardless of cisplatin eligibility","note":"Based on EV-302/KEYNOTE-A39, median overall survival 31.5 versus 16.1 months; approved 15 December 2023.","refs":[]},{"year":2024,"title":"Erdafitinib converted to full FDA approval for FGFR3-altered metastatic urothelial carcinoma","note":"For patients who progressed on at least one prior systemic therapy, approved 19 January 2024.","refs":[]},{"year":2025,"title":"Perioperative pembrolizumab plus enfortumab vedotin approved for cisplatin-ineligible muscle-invasive bladder cancer","note":"Based on KEYNOTE-905/EV-303; approved 21 November 2025.","refs":[]},{"year":2026,"title":"Perioperative pembrolizumab plus enfortumab vedotin indication expanded to cisplatin-eligible muscle-invasive bladder cancer","note":"Based on KEYNOTE-B15/EV-304 in 808 patients, a 47% reduction in event-free survival events versus neoadjuvant chemotherapy and surgery.","refs":[]}],"pipeline":["opp-nectin4-imaging-urothelial","nectin4","fdg-pet","immuno-pet"],"openProblems":["Nodal staging before radical cystectomy is poor across all imaging modalities, with pooled sensitivity of about 0.40 for CT, 0.60 for MRI and 0.56 for FDG PET/CT despite specificities around 0.91 to 0.92, meaning occult nodal metastases are commonly missed pre-operatively.","FDG PET/CT's value in the pelvis is intrinsically limited by physiological urinary excretion of the tracer, which obscures the primary tumour bed and adjacent nodes in exactly the region that matters most for surgical planning.","No international guideline consensus exists on the routine role of PET in initial staging, with US-oriented societies restricting its use and European societies recommending it for oligometastatic staging.","Only about 20% of metastatic urothelial carcinoma patients carry an FGFR2/3 alteration actionable with erdafitinib, leaving most patients without a validated targeted-therapy biomarker pathway after platinum and immunotherapy failure.","Distant disease still carries a five-year relative survival of only 9.6% despite recent enfortumab vedotin plus pembrolizumab and adjuvant immunotherapy advances, showing these regimens extend but do not yet cure metastatic disease for most patients."],"prognosis":{"text":"Survival depends strongly on stage at diagnosis. SEER reports five-year relative survival of 79.1% overall for patients diagnosed between 2016 and 2022: 98.0% for in situ disease, which is half of all cases, 73.0% for localised disease at 34% of cases, 41.8% for regional disease at 7% of cases, 9.6% for distant disease at 6% of cases, and 50.8% for unknown or unstaged disease at 3% of cases. These are population averages and do not predict any individual patient's outcome.","sources":[{"label":"SEER Cancer Stat Facts: bladder cancer","url":"https://seer.cancer.gov/statfacts/html/urinb.html"}]},"route":"/indications/urothelial-cancer/"}
{"id":"pancreatic-cancer","kind":"indication","name":"Pancreatic ductal adenocarcinoma","aka":["pancreatic cancer","PDAC","pancreatic adenocarcinoma"],"tldr":"Pancreatic cancer is one of the deadliest common cancers because it is usually found only after it has already grown into nearby structures or spread elsewhere. Surgery can cure it, but scans before the operation often cannot tell whether the tumour is truly removable, so some patients are opened up only to find the cancer has already spread too far.","summary":"Pancreatic ductal adenocarcinoma is a comparatively uncommon but highly lethal malignancy. GLOBOCAN 2024 estimates 531,318 new cases worldwide, ranking eleventh for incidence with an age-standardised rate of 4.7 per 100,000, against 490,786 deaths, ranking sixth for cancer mortality at 4.2 per 100,000; IARC's own cancer-type overview page separately describes it as the twelfth most common cancer, a minor internal discrepancy between two GLOBOCAN 2024 outputs. In the United States, SEER projects 67,530 new cases and 52,740 deaths for 2026, making it the third leading cause of cancer death, with an overall five-year relative survival of only 13.7% for patients diagnosed between 2016 and 2022. Survival tracks stage sharply: 43.6% at five years for the 15% of patients diagnosed with localised disease, 17.0% for the 28% with regional spread, and 3.4% for the 51% who already have distant metastases at diagnosis.\n\nTreatment is organised around resectability. Resectable and borderline resectable disease is treated with a combination of neoadjuvant therapy, surgery and postoperative chemotherapy, though the optimal neoadjuvant regimen remains unknown and is being tested in ongoing trials; for good-performance-status patients after resection, adjuvant mFOLFIRINOX improved median overall survival to 53.5 months against 35.5 months for gemcitabine in the PRODIGE-24 trial, with a five-year overall survival of 43.2% against 31.4%, at the cost of substantially more grade 3 or 4 toxicity. Locally advanced disease that cannot be resected because of vascular involvement is treated with chemotherapy, with chemoradiation added in some patients; the LAP07 trial showed no overall-survival benefit from adding chemoradiation to gemcitabine-based induction, though that trial predates the widespread adoption of FOLFIRINOX in this setting. Metastatic disease is treated with combination chemotherapy chosen by fitness: FOLFIRINOX improved median overall survival to 11.1 months against 6.8 months for gemcitabine alone, gemcitabine plus nab-paclitaxel improved it to 8.5 against 6.7 months, and the newer NALIRIFOX regimen gave 11.1 against 9.2 months compared with gemcitabine plus nab-paclitaxel. The 4% to 8% of patients with a germline BRCA1 or BRCA2 variant are managed with platinum-based first-line chemotherapy and, if the disease has not progressed after sixteen weeks or more, olaparib maintenance, though the POLO trial that supported this approach showed a progression-free survival benefit without a statistically significant overall-survival benefit.\n\nNuclear medicine currently has almost no defined role in this disease. NCCN materials describe PET/CT as not a routine test, useful only as a problem-solving adjunct after a dedicated pancreatic-protocol CT in high-risk patients, such as those with borderline resectable disease, a markedly elevated CA 19-9, a large primary tumour or large regional nodes, and explicitly not a substitute for high-quality CT; ESMO guidance goes further, stating that PET/CT does not add staging information in resectable disease and cannot be recommended. No FDG-PET-based or receptor-targeted imaging role for pancreatic ductal adenocarcinoma itself was identified in any guideline reviewed. The clinical gap this leaves is large: conventional CT misjudges resectability often enough that published series report 20% to 48% of patients thought resectable on CT turning out to be unresectable at surgery, and a Cochrane meta-analysis put the median pre-test probability of unresectable disease after a resectable-looking CT at 41.4%, while no validated tumour-specific serum marker exists to help, since CA 19-9 has low specificity and a normal level does not exclude recurrence. That combination, a common and morbid staging failure with no molecular imaging tool aimed at it, is the opportunity that fibroblast activation protein imaging is intended to address.","asOf":"2026-09-23","links":[{"label":"IARC GLOBOCAN 2024 pancreas factsheet","url":"https://gco.iarc.who.int/media/globocan/factsheets/cancers/13-pancreas-fact-sheet.pdf"},{"label":"SEER Cancer Stat Facts: pancreatic cancer","url":"https://seer.cancer.gov/statfacts/html/pancreas.html"},{"label":"NCI PDQ: pancreatic cancer treatment, health professional version","url":"https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq"},{"label":"FDA approval letter, nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/021660Orig1s037.pdf"},{"label":"ASCO Post: FDA approves olaparib for germline BRCA-mutated metastatic pancreatic cancer","url":"https://ascopost.com/issues/january-25-2020/fda-approves-olaparib-for-patients-with-germline-brca-mutated-metastatic-pancreatic-cancer/"},{"label":"Ferrari C et al., review of PET/CT guideline positions in pancreatic cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8394552/"}],"tags":["gastrointestinal","staging","unresectability"],"related":["fap","fdg-pet","pet-ct"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"GLOBOCAN 2024 estimates 531,318 new cases of pancreatic cancer worldwide, ranking eleventh for incidence with an age-standardised rate of 4.7 per 100,000, and 490,786 deaths, ranking sixth for cancer mortality at 4.2 per 100,000 (IARC's cancer-type overview page separately describes it as the twelfth most common cancer). SEER projects 67,530 new US cases and 52,740 US deaths in 2026, the third leading cause of cancer death in the United States, against an overall five-year relative survival of only 13.7%.","subtypes":["Resectable disease, tumours without vascular involvement","Borderline resectable disease, with vascular or local structural involvement carrying a high risk of an R1 resection","Locally advanced (unresectable) disease, with local vessel impingement or invasion precluding surgery","Metastatic disease","Germline BRCA1/BRCA2-mutated disease, present in 4% to 8% of patients with pancreatic adenocarcinoma"],"biomarkers":["CA 19-9 in serum, used to track response and progression during and after treatment despite low specificity and no tumour-specific role","Germline BRCA1/BRCA2 status, which identifies candidates for platinum-based chemotherapy and, on sustained response, olaparib maintenance","Peritoneal cytology obtained at staging laparoscopy, with a positive predictive value of 94% and specificity of 98% for unresectability, though sensitivity is only 25%"],"standardOfCare":[{"setting":"Resectable or borderline resectable disease","approach":"Neoadjuvant therapy (chemotherapy with or without chemoradiation), surgery, and postoperative chemotherapy or chemoradiation; the optimal neoadjuvant regimen is unknown. After resection, adjuvant mFOLFIRINOX is preferred for good performance status, giving a median overall survival of 53.5 months against 35.5 months for gemcitabine (PRODIGE-24), at higher toxicity.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq"}},{"setting":"Locally advanced (unresectable) disease","approach":"Chemotherapy with or without targeted therapy, or chemotherapy followed by chemoradiation in patients without metastases; the LAP07 trial found no overall-survival benefit from adding chemoradiation to gemcitabine-based induction, though FOLFIRINOX has since been widely adopted in this setting.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq"}},{"setting":"Metastatic disease, first line","approach":"FOLFIRINOX (median overall survival 11.1 versus 6.8 months for gemcitabine), gemcitabine plus nab-paclitaxel (8.5 versus 6.7 months), or NALIRIFOX (11.1 versus 9.2 months against gemcitabine plus nab-paclitaxel), chosen by performance status.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq"}},{"setting":"Metastatic disease, germline BRCA1/BRCA2-mutated","approach":"First-line platinum-based chemotherapy; olaparib maintenance can be considered after at least sixteen weeks without progression, based on the POLO trial, which showed a progression-free survival benefit (7.4 versus 3.8 months) without a statistically significant overall-survival benefit.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq"}}],"stateOfArt":["Adjuvant chemotherapy intensity now clearly changes outcomes after resection: PRODIGE-24 showed mFOLFIRINOX gave a median overall survival of 53.5 months and a five-year overall survival of 43.2%, against 35.5 months and 31.4% for gemcitabine, though 75.9% of FOLFIRINOX patients had grade 3 or 4 toxicity compared with 52.9% on gemcitabine.","In metastatic disease, regimen choice has continued to improve median overall survival incrementally, from 6.8 months on gemcitabine alone, to 11.1 months with FOLFIRINOX, to 11.1 months with the newer NALIRIFOX regimen against 9.2 months for gemcitabine plus nab-paclitaxel in the NAPOLI 3 trial.","Biomarker-selected therapy has entered the metastatic setting for the small germline BRCA1/BRCA2-mutated subgroup, but the benefit is confined to progression-free survival; NCI's own commentary on the POLO trial notes that without a proven overall-survival benefit the result lays groundwork for future combination studies rather than establishing olaparib as a standard of care on its own.","PET/CT remains a problem-solving adjunct rather than a staging tool, reserved by NCCN-derived guidance for high-risk patients such as those with borderline resectable disease or a markedly elevated CA 19-9, explicitly not a substitute for a dedicated pancreatic-protocol CT."],"history":[{"year":2011,"title":"FOLFIRINOX shown superior to gemcitabine in metastatic disease","note":"Conroy et al., ACCORD11/PRODIGE4, NEJM: median overall survival 11.1 versus 6.8 months.","refs":[]},{"year":2013,"title":"FDA approved nab-paclitaxel with gemcitabine for first-line metastatic disease","note":"Approved 6 September 2013 based on the MPACT trial of 861 patients, median overall survival 8.5 versus 6.7 months.","refs":[]},{"year":2018,"title":"PRODIGE-24 published, establishing adjuvant mFOLFIRINOX after resection","note":"Median overall survival 53.5 versus 35.5 months for gemcitabine; five-year overall survival 43.2% versus 31.4%.","refs":[]},{"year":2019,"title":"FDA approved olaparib maintenance for germline BRCA-mutated metastatic disease","note":"Approved 27 December 2019 alongside the BRACAnalysis CDx companion diagnostic, based on the POLO trial.","refs":[]},{"year":2023,"title":"NAPOLI 3 trial published","note":"NALIRIFOX gave median overall survival of 11.1 versus 9.2 months for gemcitabine plus nab-paclitaxel in 770 patients.","refs":[]}],"pipeline":["opp-fap-pancreatic-staging","fap","fapi-pet","fdg-pet"],"openProblems":["Conventional CT misjudges resectability often enough to be a clinical problem: published series report 20% to 48% of patients thought resectable on CT being found unresectable at surgery, and a Cochrane meta-analysis put the median pre-test probability of unresectable disease after a resectable-looking CT at 41.4%.","No validated tumour-specific serum marker exists; CA 19-9 has low specificity and a normal level does not preclude recurrence, so it cannot be used for screening or to reliably rule out disease.","The optimal neoadjuvant chemotherapy regimen and sequencing for borderline resectable disease is unresolved, with multiple trials (including ALLIANCE, PREOPANC-3, PANACHE-01-PRODIGE and NorPACT-01) still evaluating different approaches.","Even in the biomarker-selected germline BRCA-mutated population, PARP inhibitor maintenance has not shown a statistically significant overall-survival benefit, leaving the clinical value of that selection strategy incomplete.","Disease burden is projected to keep rising against stagnant early detection, with pancreas and liver cancers projected to surpass breast, prostate and colorectal cancers to become the second and third leading causes of cancer death by 2030."],"prognosis":{"text":"Survival remains poor across every stage. SEER reports an overall five-year relative survival of 13.7% for patients diagnosed between 2016 and 2022: 43.6% for the 15% of patients diagnosed with localised disease, 17.0% for the 28% with regional spread, 3.4% for the 51% with distant metastases at diagnosis, and 12.5% for the 5% left unstaged. These are population averages and say nothing about an individual patient.","sources":[{"label":"SEER Cancer Stat Facts: pancreatic cancer","url":"https://seer.cancer.gov/statfacts/html/pancreas.html"}]},"route":"/indications/pancreatic-cancer/"}
{"id":"gastric-oesophageal-cancer","kind":"indication","name":"Gastric and gastro-oesophageal junction adenocarcinoma","aka":["stomach cancer","gastric cancer","GEJ adenocarcinoma","oesophagogastric adenocarcinoma"],"tldr":"Cancer of the stomach or the junction where the gullet meets the stomach is common worldwide and still mostly found late, which is why survival is poor for most patients. Treatment now depends heavily on testing the tumour for a handful of markers that decide which targeted drugs and immunotherapies can be used.","summary":"Gastric and gastro-oesophageal junction (GEJ) adenocarcinoma is a heterogeneous disease spanning intestinal and diffuse (signet-ring) histological subtypes and a spectrum from proximal junctional tumours to distal gastric tumours. GLOBOCAN 2024 estimates rank stomach cancer fifth worldwide for both incidence and mortality, with 980,286 new cases and 641,554 deaths a year. In the United States, SEER projects 31,510 new cases and 10,740 deaths for 2026, and five-year relative survival is 39.8% overall, but that figure conceals an enormous stage gradient: 78.1% for localised disease, which is 32% of cases, 39.0% for regional disease at 23%, and 8.1% for distant disease at 35%. Most Western patients present with regional or distant disease, which is why the field has organised itself around biomarker-directed systemic therapy rather than around early detection.\n\nTreatment splits by resectability and, in the metastatic setting, by biomarker. Resectable gastric or GEJ adenocarcinoma is treated with perioperative FLOT chemotherapy, which the FLOT4 trial showed improves overall survival over ECF/ECX (median 50 versus 35 months), combined with D2 lymphadenectomy at surgery; the phase 3 MATTERHORN trial has since shown that adding durvalumab to FLOT improves event-free survival further and NCCN restricts the category-1 recommendation for that combination to PD-L1-positive tumours. Resectable oesophageal or junctional (Siewert I-II) adenocarcinoma has long been treated with neoadjuvant chemoradiotherapy per the CROSS trial, which gave a median overall survival of 49.4 versus 24.0 months and a 13 percentage point absolute ten-year survival benefit, but the newer ESOPEC trial reports perioperative FLOT outperforming CROSS in this population (median overall survival 66 versus 37 months), so practice is shifting. In the metastatic setting, first-line therapy is chosen by testing for HER2 (trastuzumab, with pembrolizumab added if PD-L1 CPS is at least 1), PD-L1 CPS in HER2-negative disease (nivolumab or pembrolizumab added to chemotherapy), CLDN18.2 positivity in HER2-negative disease (zolbetuximab), and mismatch-repair status, with pembrolizumab recommended second line for MSI-H/dMMR disease; trastuzumab deruxtecan is approved second line after trastuzumab progression.\n\nNuclear medicine's role is limited and this is the central problem the field is trying to solve. FDG PET/CT is an adjunct to CT rather than a replacement for staging laparoscopy, and NCCN guideline text records FDG-PET/CT accuracy of 68% in preoperative staging against 47% for FDG-PET alone and 53% for CT alone, while a Dutch prospective cohort found FDG-PET/CT sensitivity of only 33% for distant metastases against a specificity of 97%, and staging laparoscopy sensitivity of 82% for peritoneal disease against 78% specificity. FDG uptake is characteristically low in diffuse and signet-ring histology, a common subtype in gastric cancer, so the modality is weakest exactly where peritoneal spread most needs to be excluded; PET sensitivity for peritoneal carcinomatosis has been reported at only about 50%. This gap between what biomarker testing can select for systemically and what imaging can see anatomically, particularly for peritoneal disease, is the opening that new imaging targets such as CLDN18.2 and FAPI tracers are being explored to fill.","asOf":"2026-09-23","links":[{"label":"IARC GLOBOCAN 2024 stomach factsheet","url":"https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf"},{"label":"SEER Cancer Stat Facts: stomach cancer","url":"https://seer.cancer.gov/statfacts/html/stomach.html"},{"label":"NCI PDQ: gastric cancer treatment, health professional version","url":"https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq"},{"label":"FLOT4 trial, Al-Batran et al., Lancet 2019 (PubMed)","url":"https://pubmed.ncbi.nlm.nih.gov/30982686/"},{"label":"CROSS trial, van Hagen et al., NEJM 2012","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1112088"},{"label":"FDA approval of zolbetuximab-clzb (Vyloy) for CLDN18.2-positive gastric/GEJ adenocarcinoma","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma"}],"tags":["gastrointestinal","biomarker-selected","peritoneal staging"],"related":["cldn18-2","her2","fdg-pet","fap"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"GLOBOCAN 2024 estimates rank stomach cancer fifth worldwide for incidence, with 980,286 new cases a year (age-standardised rate 8.9 per 100,000), and fifth for mortality, with 641,554 deaths a year (age-standardised rate 5.6 per 100,000). SEER projects 31,510 new US cases and 10,740 US deaths in 2026. Five-year relative survival (SEER, 2016-2022) is 39.8% overall: 78.1% for the 32% of patients diagnosed with localised disease, 39.0% for the 23% with regional disease, and 8.1% for the 35% with distant disease.","subtypes":["Gastric adenocarcinoma, intestinal type","Gastric adenocarcinoma, diffuse type (signet-ring cell)","Gastro-oesophageal junction (Siewert I-II) adenocarcinoma","HER2-positive disease","CLDN18.2-positive, HER2-negative disease","Mismatch-repair deficient / microsatellite instability-high disease"],"biomarkers":["HER2, by IHC with reflex FISH for IHC 2+ equivocal cases, positive in about 22.1% of gastric/GEJ cancers overall in the ToGA screening cohort, higher in GEJ (33.2%) and intestinal-type (32.2%) tumours","PD-L1 Combined Positive Score by IHC (28-8 or 22C3 pharmDx), with roughly 80% of patients CPS 1 or above, 60% CPS 5 or above and 50% CPS 10 or above in the CheckMate 649 population","CLDN18.2 by IHC (VENTANA CLDN18 43-14A RxDx Assay), positive when at least 75% of tumour cells show moderate to strong membranous staining, seen in about 38% of patients screened in the SPOTLIGHT and GLOW trials","Mismatch repair / microsatellite instability, by IHC for MLH1/MSH2/MSH6/PMS2 or PCR/NGS panels, pooled MSI-H prevalence around 11% overall and more common in early-stage tumours than in metastatic disease"],"standardOfCare":[{"setting":"Resectable gastric or GEJ adenocarcinoma","approach":"Perioperative FLOT chemotherapy with D2 lymphadenectomy at surgery; the MATTERHORN trial has shown that adding durvalumab to FLOT improves event-free survival, and NCCN restricts the category-1 recommendation for durvalumab-FLOT to PD-L1-positive (CPS or TAP at least 1) tumours.","refs":[],"guideline":{"url":"https://www.nccn.org/patients/guidelines/content/PDF/stomach-patient.pdf"}},{"setting":"Resectable oesophageal/junctional (Siewert I-II) adenocarcinoma","approach":"Neoadjuvant chemoradiotherapy per the CROSS regimen has been standard, but the ESOPEC trial reports perioperative FLOT gives superior overall survival, so FLOT is emerging as preferred where feasible.","refs":[],"guideline":{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1112088"}},{"setting":"Metastatic disease, first line, HER2-positive","approach":"Trastuzumab with fluoropyrimidine- and platinum-based chemotherapy, with pembrolizumab added when PD-L1 CPS is at least 1.","refs":[],"guideline":{"url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-positive-gastric-adenocarcinomas"}},{"setting":"Metastatic disease, first line, HER2-negative","approach":"Chemotherapy plus nivolumab (regardless of PD-L1 status) or pembrolizumab; zolbetuximab is added for CLDN18.2-positive tumours. Pembrolizumab alone is recommended second line for MSI-H/dMMR disease.","refs":[],"guideline":{"url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma"}}],"stateOfArt":["The phase 3 MATTERHORN trial established that adding durvalumab to perioperative FLOT improves event-free survival over FLOT alone in resectable gastric/GEJ adenocarcinoma, and this durvalumab-FLOT combination is now described as the new standard of care for all-comers, though NCCN currently restricts its category-1 recommendation to PD-L1-positive tumours.","The ESOPEC trial has reported that perioperative FLOT gives a median overall survival of 66 months versus 37 months for neoadjuvant CROSS chemoradiotherapy in resectable oesophageal/GEJ adenocarcinoma, challenging more than a decade of CROSS as the reference standard for that population.","Biomarker testing at diagnosis now routes patients into distinct first-line regimens by HER2, PD-L1 CPS, CLDN18.2 and mismatch-repair status, so molecular characterisation has effectively become as important as anatomical staging for treatment selection.","FDG PET/CT remains an adjunct to CT rather than a replacement for staging laparoscopy, with NCCN guideline text recording combined PET/CT accuracy of 68% in preoperative staging against 53% for CT alone, reflecting persistently limited sensitivity for peritoneal disease."],"history":[{"year":2010,"title":"FDA approved trastuzumab (Herceptin) with chemotherapy for first-line HER2-positive metastatic gastric/GEJ adenocarcinoma","note":"Based on the ToGA trial; approved in October 2010.","refs":[]},{"year":2012,"title":"CROSS trial established neoadjuvant chemoradiotherapy as standard for resectable oesophageal/junctional cancer","note":"Median overall survival 49.4 versus 24.0 months for surgery alone.","refs":[]},{"year":2019,"title":"FLOT4 trial established perioperative FLOT as standard for resectable gastric/GEJ adenocarcinoma","note":"Median overall survival 50 versus 35 months against ECF/ECX.","refs":[]},{"year":2021,"title":"FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive gastric/GEJ adenocarcinoma after prior trastuzumab","note":"Approved 15 January 2021, based on DESTINY-Gastric01.","refs":[]},{"year":2021,"title":"FDA approved nivolumab plus chemotherapy first line for advanced gastric, GEJ and oesophageal adenocarcinoma regardless of PD-L1 status","note":"Approved 16 April 2021, based on CheckMate 649.","refs":[]},{"year":2021,"title":"FDA granted accelerated approval to pembrolizumab plus trastuzumab plus chemotherapy for first-line HER2-positive, PD-L1 CPS 1 or above gastric/GEJ adenocarcinoma","note":"Approved 5 May 2021 based on KEYNOTE-811; converted to full approval in March 2025.","refs":[]},{"year":2024,"title":"FDA approved zolbetuximab-clzb (Vyloy) with chemotherapy first line for HER2-negative, CLDN18.2-positive gastric/GEJ adenocarcinoma","note":"Approved 18 October 2024, with simultaneous approval of the VENTANA CLDN18 (43-14A) RxDx companion diagnostic.","refs":[]},{"year":2025,"title":"ESOPEC trial reported perioperative FLOT superior to neoadjuvant CROSS for resectable oesophageal/GEJ adenocarcinoma","note":"Median overall survival 66 versus 37 months.","refs":[]},{"year":2025,"title":"MATTERHORN trial showed perioperative durvalumab plus FLOT improves event-free survival over FLOT alone in resectable gastric/GEJ adenocarcinoma","note":"Published in NEJM 2025;393:217-30.","refs":[]}],"pipeline":["opp-cldn18-2-imaging-gastric","cldn18-2","her2","fdg-pet"],"openProblems":["Peritoneal metastases are missed by all cross-sectional and PET imaging and remain reliably detectable only by invasive staging laparoscopy with lavage cytology, and even that is imperfect: one Dutch study found tumour-guided cfDNA analysis detected peritoneal disease with 91% sensitivity against 64% for conventional cytology.","Cytology interpretation at staging laparoscopy is not standardised between centres, with a multicentre Japanese survey finding more than a tenfold variation in cytology positivity rates, from 2.1% to 28.3%, tied to differences in laboratory methodology.","Diffuse-type, signet-ring and mucinous histology is systematically under-staged by CT, PET and EUS alike, so a common histological subgroup has no noninvasive staging modality it can be confidently assessed with.","Even a macroscopically negative staging laparoscopy misses disease: 13% of such patients have positive cytology, and 29% of cytology-negative patients still develop a peritoneal recurrence after apparently complete R0 resection.","Emerging 68Ga-FAPI PET tracers have been proposed as a possible partial solution to the peritoneal and diffuse-histology staging gap, but this is not yet adopted into any guideline."],"prognosis":{"text":"Survival tracks stage at diagnosis closely. SEER reports five-year relative survival of 39.8% overall for patients diagnosed between 2016 and 2022: 78.1% for localised disease, which is 32% of cases, 39.0% for regional disease at 23% of cases, and 8.1% for distant disease at 35% of cases, reflecting that most patients in Western countries present with advanced, non-curable disease.","sources":[{"label":"SEER Cancer Stat Facts: stomach cancer","url":"https://seer.cancer.gov/statfacts/html/stomach.html"}]},"route":"/indications/gastric-oesophageal-cancer/"}
{"id":"breast-triple-negative","kind":"indication","name":"Triple-negative breast cancer","aka":["TNBC"],"tldr":"Triple-negative breast cancer lacks the three commonest treatment targets, so hormone therapy and HER2 drugs do not work against it and treatment rests on chemotherapy, immunotherapy and antibody-drug conjugates. It is more aggressive than most breast cancer and harder to treat once it has spread.","summary":"Triple-negative breast cancer is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression on the tumour. IARC's GLOBOCAN programme estimated 2.3 million new breast cancer cases and 670,000 breast cancer deaths worldwide in 2022, making it the second most common cancer type after lung cancer, with 2.43 million new cases estimated for 2024; globally one in 20 women will be diagnosed with breast cancer in her lifetime and one in 70 will die of it. In the United States, SEER projects 321,910 new breast cancer cases and 42,140 deaths in 2026, with overall five-year relative survival of 91.9% for 2016 to 2022. Triple-negative disease makes up about 15% of all breast cancers by NCI's figures, with other reviews estimating a range of 10% to 15%, and it carries a markedly worse prognosis once it has spread than breast cancer overall.\n\nTreatment is organised by stage and by a small number of biomarkers rather than by the hormone and HER2 pathways used elsewhere in breast cancer. High-risk early-stage disease is treated with neoadjuvant pembrolizumab plus chemotherapy continued as adjuvant pembrolizumab after surgery, approved by the FDA in 2021 on the strength of KEYNOTE-522, with long-term follow-up now showing a 34% reduction in the risk of death. Patients left with residual disease after neoadjuvant chemotherapy may receive adjuvant pembrolizumab, off-label capecitabine, or adjuvant olaparib for one year if they carry a germline BRCA mutation, the last approved in 2022 on the OlympiA trial. In the metastatic setting, pembrolizumab is added to chemotherapy only when PD-L1 combined positive score is 10 or more, and 2026 brought two further first-line approvals for Trop-2-directed antibody-drug conjugates: sacituzumab govitecan, as monotherapy for patients ineligible for immunotherapy or combined with pembrolizumab for PD-L1-high disease, and datopotamab deruxtecan for patients ineligible for PD-1/PD-L1 therapy.\n\nNuclear medicine has only a general, not a triple-negative-specific, role in this disease. FDG PET/CT is not indicated for routine staging of early breast cancer and is reserved for equivocal conventional imaging or systemic staging of stage IV or recurrent disease. Fluoroestradiol PET, approved in 2020 as an adjunct to biopsy for detecting oestrogen-receptor-positive lesions and later added to NCCN guidelines for ER-positive and lobular disease, is by definition unable to characterise triple-negative tumours, since it images the very receptor these tumours lack, and it cannot assess HER2 or progesterone receptor status either. No FDA-approved molecular imaging agent identifies triple-negative lesions specifically, predicts response to a TNBC-directed drug, or serves as a companion diagnostic for pembrolizumab, sacituzumab govitecan, datopotamab deruxtecan or olaparib in this disease; PD-L1 and BRCA status are established entirely by tissue-based testing.","asOf":"2026-09-23","links":[{"label":"IARC press release: global cancer burden 2022","url":"https://www.iarc.who.int/wp-content/uploads/2025/02/pr361_E.pdf"},{"label":"NCI: What Is Triple-Negative Breast Cancer (TNBC)?","url":"https://www.cancer.gov/types/breast/breast-cancer-types/triple-negative"},{"label":"SEER Cancer Stat Facts: female breast cancer","url":"https://seer.cancer.gov/statfacts/html/breast.html"},{"label":"FDA: approval of sacituzumab govitecan-hziy monotherapy and with pembrolizumab, first line","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line"},{"label":"FDA: approval of datopotamab deruxtecan-dlnk for unresectable or metastatic TNBC","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-triple-negative-breast-cancer"},{"label":"Merck: FDA approval of pembrolizumab for high-risk early-stage TNBC (KEYNOTE-522)","url":"https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/"}],"tags":["breast","immunotherapy","trop2"],"related":["trop2","trop2-pet","fdg-pet","fluoroestradiol-f18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"breast","burden":"IARC GLOBOCAN estimated 2.3 million new breast cancer cases and 670,000 breast cancer deaths worldwide in 2022, rising to an estimated 2.43 million new cases in 2024, and ranks it the second most common cancer type worldwide after lung cancer; globally one in 20 women will be diagnosed with breast cancer in her lifetime and one in 70 will die of it. In the United States, SEER projects 321,910 new cases and 42,140 deaths in 2026, with an age-adjusted incidence of 132.5 and mortality of 18.9 per 100,000 women per year, and overall five-year relative survival of 91.9% based on 2016-2022 data. Triple-negative breast cancer, defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression, accounts for about 15% of all breast cancers per NCI, with other reviews estimating 10% to 15%.","subtypes":["Early-stage, high-risk TNBC treated with neoadjuvant chemoimmunotherapy","Residual disease after neoadjuvant chemotherapy (non-pathological complete response)","Germline BRCA1/2-mutated, HER2-negative, high-risk early disease","Metastatic or locally recurrent TNBC with PD-L1 combined positive score of 10 or more","Metastatic TNBC in patients ineligible for PD-1/PD-L1 inhibitor therapy"],"biomarkers":["Oestrogen receptor (ER) by immunohistochemistry, required to be below 1% positivity for a triple-negative diagnosis","Progesterone receptor (PR) by immunohistochemistry, also required to be negative","HER2 by immunohistochemistry/in-situ hybridisation, required to be negative (IHC 0-2+ or ISH non-amplified)","Germline BRCA1/2 mutation status, reported in roughly 9% to 35% of TNBC cohorts, which determines eligibility for adjuvant or metastatic olaparib","PD-L1 combined positive score by the 22C3 pharmDx assay, required to be 10 or more to add pembrolizumab in first-line metastatic disease"],"standardOfCare":[{"setting":"Early-stage, high-risk TNBC (neoadjuvant and adjuvant)","approach":"Pembrolizumab combined with chemotherapy is given before surgery and continued as a single agent after surgery, approved by the FDA on 26 July 2021 based on KEYNOTE-522, which showed a pathological complete response of 63% versus 56% and an event-free survival hazard ratio of 0.63; long-term follow-up at a median of 75.1 months showed a 34% reduction in the risk of death.","refs":[],"guideline":{"url":"https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/"}},{"setting":"Residual disease after neoadjuvant chemotherapy (non-pCR)","approach":"NCCN education materials list adjuvant pembrolizumab if a pembrolizumab-containing regimen was given preoperatively, adjuvant capecitabine for six to eight cycles based on the CREATE-X trial (used off-label, NCCN category 2A), or adjuvant olaparib for one year with a germline BRCA mutation, with no established evidence on sequencing or combining the three.","refs":[],"guideline":{"url":"https://education.nccn.org/sites/default/files/course/2023-02/2_Neoadjuvant.Adjuvant%20Treatment_NCCNbc23_v2.pdf"}},{"setting":"Early-stage, germline BRCA-mutated, HER2-negative, high-risk disease","approach":"Adjuvant olaparib for one year received accelerated FDA approval on 11 March 2022 based on OlympiA, which showed three-year invasive disease-free survival of 85.9% versus 77.1% (hazard ratio 0.58) and an updated overall survival hazard ratio of 0.68, a 32% reduction in the risk of death.","refs":[],"guideline":{"url":"https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-approved-in-the-us-as-adjuvant-treatment-for-patients-with-germline-brca-mutated-her2-negative-high-risk-early-breast-cancer.html"}},{"setting":"Metastatic or locally recurrent TNBC, first line, PD-L1 CPS 10 or more","approach":"Pembrolizumab plus chemotherapy received accelerated approval on 13 November 2020 based on KEYNOTE-355, which showed a progression-free survival hazard ratio of 0.65, and converted to full approval in July 2021 on final overall survival data of 23.0 versus 16.1 months (hazard ratio 0.73); the PD-L1 IHC 22C3 pharmDx assay was approved as the companion diagnostic.","refs":[],"guideline":{"url":"https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-in-combination-with-chemotherapy-for-patients-with-locally-recurrent-unresectable-or-metastatic-triple%E2%80%91negative-breast-cancer-whose/"}},{"setting":"Metastatic TNBC, first line","approach":"Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, was approved on 24 June 2026 as first-line monotherapy for patients ineligible for PD-1/PD-L1 therapy (ASCENT-03) or combined with pembrolizumab for PD-L1 CPS 10 or more disease (ASCENT-04/KEYNOTE-D19); datopotamab deruxtecan, another Trop-2-directed antibody-drug conjugate, was approved on 22 May 2026 for patients ineligible for PD-1/PD-L1 therapy based on TROPION-Breast02, with median overall survival of 23.7 versus 18.7 months (hazard ratio 0.79) and a progression-free survival hazard ratio of 0.57.","refs":[],"guideline":{"url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line"}}],"stateOfArt":["Metastatic first-line treatment for TNBC changed twice in 2026: sacituzumab govitecan was approved as monotherapy for patients ineligible for immunotherapy or combined with pembrolizumab for PD-L1 CPS 10 or more disease, and datopotamab deruxtecan was separately approved for patients ineligible for PD-1/PD-L1 therapy. Both are Trop-2-directed antibody-drug conjugates, marking a shift from cytotoxic chemotherapy backbones toward targeted ADCs even in a disease defined by the absence of a single dominant receptor target.","Long-term follow-up of KEYNOTE-522 at a median of 75.1 months showed that neoadjuvant and adjuvant pembrolizumab reduces the risk of death by 34% compared with chemotherapy alone in high-risk early-stage TNBC, confirming that the early pathological complete response benefit translates into a durable survival advantage.","Receptor status is not fixed over the course of disease: the French ESME cohort found a 27.0% total discordance rate for hormone receptor and/or HER2 status between the primary tumour and metastases, with ER status changing in 15.1% of cases and PR status in 31.1%, which is why ASCO/CAP guidance calls for retesting receptors at metastatic recurrence."],"history":[{"year":2020,"title":"FDA grants accelerated approval to pembrolizumab plus chemotherapy for PD-L1 CPS 10 or more metastatic TNBC","note":"Based on KEYNOTE-355, which gave a progression-free survival hazard ratio of 0.65; converted to full approval in July 2021 on final overall survival of 23.0 versus 16.1 months.","refs":[]},{"year":2021,"title":"FDA approves pembrolizumab as neoadjuvant plus chemotherapy then adjuvant monotherapy for high-risk early-stage TNBC","note":"Based on KEYNOTE-522, which showed a pathological complete response of 63% versus 56%.","refs":[]},{"year":2022,"title":"FDA grants accelerated approval to adjuvant olaparib for germline BRCA-mutated, HER2-negative, high-risk early breast cancer","note":"Based on OlympiA, with three-year invasive disease-free survival of 85.9% versus 77.1%.","refs":[]},{"year":2026,"title":"FDA approves datopotamab deruxtecan for first-line metastatic TNBC in patients ineligible for PD-1/PD-L1 therapy","note":"Based on TROPION-Breast02, with median overall survival of 23.7 versus 18.7 months, approved 22 May 2026.","refs":[]},{"year":2026,"title":"FDA approves sacituzumab govitecan, alone or with pembrolizumab, for first-line metastatic TNBC","note":"Based on ASCENT-03 and ASCENT-04/KEYNOTE-D19, approved 24 June 2026.","refs":[]}],"pipeline":["opp-trop2-imaging-heterogeneity","trop2","trop2-pet","fdg-pet"],"openProblems":["TNBC lacks all three routinely druggable receptors, so chemotherapy, immunotherapy and antibody-drug conjugates remain the only broadly available systemic options, and no reliably hormone-receptor-directed adjuvant target exists outside germline BRCA carriers.","The disease is molecularly and spatially heterogeneous, which undermines single-biomarker prognostic and predictive models; spatial profiling has shown sharp shifts in PAM50 subtype and immune infiltration within the same tumour.","Resistance to immune checkpoint inhibition is common and appears tied to homologous-recombination status: BRCA-mutant, homologous-recombination-deficient tumours tend to have more tumour-infiltrating lymphocytes and respond better to immunotherapy, while homologous-recombination-proficient tumours are often refractory.","Receptor status can change between the primary tumour and a metastasis at rates high enough to alter treatment eligibility, meaning a single primary-tumour biopsy can misclassify a patient's disease over time.","No FDA-approved nuclear medicine agent identifies triple-negative lesions specifically or predicts response to TNBC-directed therapy; fluoroestradiol PET, the one approved receptor-imaging breast agent, explicitly cannot assess HER2 or progesterone receptor status and has no defined role in oestrogen-receptor-negative disease."],"prognosis":{"text":"Five-year relative survival for TNBC falls sharply with stage. NCI reports 91% for localised disease, 66% for regional disease and 12% for metastatic disease in women diagnosed between 2015 and 2021. A closely related SEER-derived dataset cited by the American Cancer Society gives slightly different figures for the same period, 92%, 67% and 15% respectively, with an all-stage combined figure of 78%; the two published tables have not been reconciled to a single SEER*Explorer query. For comparison, five-year relative survival across all breast cancer combined is 91.9% in SEER's most recent data, from 2016 to 2022.","sources":[{"label":"NCI: What Is Triple-Negative Breast Cancer (TNBC)?","url":"https://www.cancer.gov/types/breast/breast-cancer-types/triple-negative"},{"label":"SEER Cancer Stat Facts: female breast cancer","url":"https://seer.cancer.gov/statfacts/html/breast.html"}]},"route":"/indications/breast-triple-negative/"}
{"id":"primary-aldosteronism","kind":"indication","name":"Primary aldosteronism","aka":["PA","primary hyperaldosteronism","hyperaldosteronism"],"tldr":"Primary aldosteronism is a hormonal condition in which one or both adrenal glands make too much of a hormone that raises blood pressure. It is a common but badly under-diagnosed cause of hypertension, usually flagged by a blood test, and curable with surgery when only one gland is overactive.","summary":"Primary aldosteronism is the most common endocrine cause of secondary hypertension, with the 2025 Endocrine Society Clinical Practice Guideline estimating a prevalence of 5% to 14% among hypertensive people seen in primary care and up to 30% in referral centres, rising to a range of 11.3% to 29.1% in resistant hypertension and 28.1% when hypertension is accompanied by hypokalaemia. Despite guideline endorsement of near-universal screening, actual testing is rare: fewer than 1% of a Canadian cohort of one million hypertensive individuals had ever been screened, and a large United States electronic health registry study found that only 2.1% of people meeting criteria for resistant hypertension were screened within two years of becoming eligible. The clinical cost of that gap is real rather than theoretical, since a meta-analysis of 31 studies covering 3,838 people with primary aldosteronism and 9,284 with essential hypertension found significantly higher odds of stroke, coronary artery disease, atrial fibrillation and heart failure, and a separate meta-analysis of 46 studies found higher odds of albuminuria and proteinuria, all over and above the effect of blood pressure itself.\n\nCare follows a screen, confirm, subtype and treat pathway. The guideline suggests screening all individuals with hypertension using the aldosterone to renin ratio, with potassium checked alongside to avoid a false negative from hypokalaemia. A positive screen with an intermediate probability of lateralizing disease can go on to aldosterone-suppression testing, and anyone considering surgery should have adrenal CT plus adrenal vein sampling to decide whether disease is unilateral or bilateral, with a selectivity index above 5:1 confirming successful catheterisation and a lateralization index above 4:1 indicating a dominant side; a minority of young patients under 35 with marked disease and a clear adenoma over 1 cm on CT can skip adrenal vein sampling. Lateralizing disease in a willing surgical candidate is treated with unilateral adrenalectomy, while bilateral disease, or lateralizing disease in someone who cannot or will not have surgery, is treated with a mineralocorticoid receptor antagonist, with spironolactone preferred over other agents for cost and availability and started at 12.5 to 25 mg daily. Every patient with an adrenal adenoma is also suggested to have a 1-mg overnight dexamethasone suppression test to catch co-existing mild autonomous cortisol secretion, reported in roughly 5% to 27% of people with primary aldosteronism depending on the series.\n\nNuclear medicine's role remains explicitly investigational rather than a guideline recommendation: the 2025 guideline discusses PET-based imaging with aldosterone synthase-specific molecules only under Research Considerations, as a possible way to reduce reliance on adrenal vein sampling and its interventional radiology expertise. Two tracers dominate that literature. Dexamethasone-suppressed 11C-metomidate PET-CT was noninferior to adrenal vein sampling for lateralization in 93 surgically treated patients in the guideline's cited study, but an independent prospective head-to-head series found its concordance with adrenal vein sampling was only 51%, no better than adrenal CT at 53%, and practical use is limited by the short half-life of carbon-11. 68Ga-pentixafor, which targets CXCR4 receptors that are overexpressed in aldosterone-producing adenomas but low or undetectable in normal adrenal tissue and nonfunctioning adenomas, was noninferior to adrenal vein sampling in 63 surgically treated patients in the guideline's cited study, and an independent meta-analysis reported 80% sensitivity and 91.5% specificity for lateralization with a 79% concordance rate to adrenal vein sampling across five studies, making it the more promising of the two candidates even though neither has displaced adrenal vein sampling as the guideline-endorsed standard.","asOf":"2026-09-23","links":[{"label":"2025 Endocrine Society Primary Aldosteronism Clinical Practice Guideline, JCEM","url":"https://academic.oup.com/jcem/article/110/9/2453/8196671"},{"label":"Endocrine Society guideline summary page","url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"},{"label":"Endocrine Society news release calling for increased screening","url":"https://www.endocrine.org/news-and-advocacy/news-room/2025/endocrine-society-guideline-calls-for-increased-screening-for-common-cause-of-high-blood-pressure"},{"label":"Screening rates for primary aldosteronism in resistant hypertension, a cohort study","url":"https://med.stanford.edu/content/dam/sm/urology/JJimages/publications/Screening-rates-for-primary-aldosteronism-in-resistant-hypertension-A-cohort-study.pdf"},{"label":"CCJM interpretive review of primary aldosteronism management","url":"https://www.ccjm.org/content/93/9/515"},{"label":"Universal screening for primary aldosteronism in hypertensive patients","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12459304/"}],"tags":["endocrine","hypertension","screening"],"related":["cxcr4","ga-68-pentixafor","opp-cxcr4-primary-aldosteronism","ga-68","c-11"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"The 2025 Endocrine Society guideline estimates primary aldosteronism prevalence at 5% to 14% of hypertensive people in primary care and up to 30% in referral centres, rising to 11.3% to 29.1% in resistant hypertension and 28.1% in hypertension with hypokalaemia. Screening is nonetheless rare: fewer than 1% of a Canadian cohort of one million hypertensive people had been screened, and only 2.1% of eligible people with resistant hypertension in a large US registry cohort were screened within two years of meeting criteria. A meta-analysis of 31 studies found increased odds of stroke, coronary artery disease, atrial fibrillation and heart failure compared with essential hypertension, and a separate meta-analysis of 46 studies found increased odds of albuminuria and proteinuria.","subtypes":["Unilateral aldosterone-producing adenoma (lateralizing disease), the form treated by adrenalectomy","Bilateral adrenal hyperplasia (bilateral primary aldosteronism), treated medically rather than surgically","Primary aldosteronism with mild autonomous cortisol co-secretion, found on 1-mg dexamethasone suppression testing in roughly 5% to 27% of cases depending on the series"],"biomarkers":["Aldosterone to renin ratio (ARR), the screening test; a ratio above 20 with suppressed renin and aldosterone above threshold indicates a positive screen and triggers confirmatory or subtyping workup","Serum potassium, measured alongside aldosterone and renin to avoid a false negative, since low potassium can artificially lower aldosterone","Aldosterone suppression testing (salt loading, fludrocortisone or saline infusion), used selectively when screening suggests an intermediate probability of lateralizing disease","1-mg overnight dexamethasone suppression test, recommended in all patients with an adrenal adenoma to detect mild autonomous cortisol co-secretion","Adrenal vein sampling selectivity index (adrenal vein to IVC cortisol ratio) and lateralization index (cortisol-corrected aldosterone ratio, high side to low side), used to confirm successful catheterisation and determine unilateral versus bilateral disease","Renin during mineralocorticoid receptor antagonist therapy, monitored to titrate dose, since persistently suppressed renin on treatment is associated with higher cardiovascular event rates"],"standardOfCare":[{"setting":"All individuals with hypertension","approach":"Screening for primary aldosteronism is suggested for everyone with hypertension, using the aldosterone to renin ratio alongside serum potassium for accurate interpretation.","refs":[],"guideline":{"url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"}},{"setting":"Positive screen, intermediate probability of lateralizing disease","approach":"Aldosterone-suppression testing is suggested when screening results give an intermediate probability of lateralizing disease and the patient wants to pursue surgical eligibility.","refs":[],"guideline":{"url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"}},{"setting":"Confirmed primary aldosteronism considering surgery","approach":"Adrenal lateralization with CT scanning and adrenal vein sampling is suggested before deciding between medical and surgical treatment, except in young patients under 35 with marked disease and a clear unilateral adenoma over 1 cm on CT, where adrenalectomy without prior adrenal vein sampling can be considered.","refs":[],"guideline":{"url":"https://academic.oup.com/jcem/article/110/9/2453/8196671"}},{"setting":"Lateralizing disease, surgical candidate who wants surgery","approach":"Unilateral adrenalectomy should be considered preferable over nonspecific antihypertensive therapy.","refs":[],"guideline":{"url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"}},{"setting":"Bilateral disease, or lateralizing disease in a non-surgical candidate","approach":"Medical treatment with a mineralocorticoid receptor antagonist should be considered preferable over nonspecific antihypertensive therapy, with spironolactone preferred over other agents for cost and availability and started at 12.5 to 25 mg daily, titrated to blood pressure, potassium and renin.","refs":[],"guideline":{"url":"https://academic.oup.com/jcem/article/110/9/2453/8196671"}},{"setting":"All patients with primary aldosteronism and an adrenal adenoma","approach":"A 1-mg overnight dexamethasone suppression test is suggested to screen for mild autonomous cortisol co-secretion, which can complicate interpretation of adrenal vein sampling and prompts further Cushing syndrome evaluation if positive.","refs":[],"guideline":{"url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"}}],"stateOfArt":["The 2025 Endocrine Society Clinical Practice Guideline, published in the Journal of Clinical Endocrinology and Metabolism and presented at ENDO 2025, replaces the 2016 guideline and pushes for substantially more widespread screening than currently occurs in practice.","The European Society of Cardiology's 2024 hypertension guidelines went further, advancing to a Class IIa, Level B recommendation for systematic aldosterone to renin ratio screening in all adults with confirmed hypertension.","Positron emission tomography with aldosterone synthase-specific tracers is discussed only as a research consideration rather than a recommendation, aimed at eventually reducing reliance on adrenal vein sampling and the specialised interventional radiology it requires.","Of the tracers studied, 68Ga-pentixafor targeting CXCR4 has shown more consistent concordance with adrenal vein sampling than dexamethasone-suppressed 11C-metomidate, though neither has been adopted as a guideline-endorsed subtyping tool."],"history":[{"year":2016,"title":"Prior Endocrine Society clinical practice guideline on primary aldosteronism case detection, diagnosis and treatment","note":"The guideline subsequently replaced and updated by the 2025 version.","refs":[]},{"year":2024,"title":"European Society of Cardiology hypertension guidelines advanced to systematic aldosterone-renin ratio screening","note":"Recommended for all adults with confirmed hypertension at Class IIa, Level B.","refs":[]},{"year":2025,"title":"New Endocrine Society Clinical Practice Guideline on primary aldosteronism published and presented at ENDO 2025","note":"Called for increased screening for this common hormonal cause of high blood pressure; published online 14 July 2025 and in the September 2025 print issue of JCEM.","refs":[]}],"pipeline":["opp-cxcr4-primary-aldosteronism","cxcr4","ga-68-pentixafor","pet-ct"],"openProblems":["Screening is guideline-endorsed for almost all hypertensive patients but is essentially never performed in practice, with fewer than 1% screened in a Canadian cohort of one million hypertensive individuals.","Even in resistant hypertension, the highest-risk group, only about 1 in 50 eligible patients receive guideline-recommended screening within two years of becoming eligible.","Adrenal CT alone misclassifies a substantial share of patients relative to adrenal vein sampling, with one evidence summary reporting CT or MRI misdiagnosed the cause of disease in 37.8% of individuals, and CT-based management alone is associated with lower odds of biochemical cure after surgery.","Adrenal vein sampling itself is technically demanding and provision is uneven, with success rates depending heavily on operator experience and one international study finding it was completed in only 77% of confirmed cases on average across centres, ranging from 19% to 100%.","Functional imaging that could reduce reliance on adrenal vein sampling remains investigational, with mixed evidence between candidate tracers and no PET or scintigraphy option currently endorsed by guideline recommendation for routine subtyping."],"route":"/indications/primary-aldosteronism/"}
{"id":"opp-dll3-imaging-sclc","kind":"opportunity","name":"DLL3 imaging for small-cell lung cancer","aka":["DLL3 PET","delta-like ligand 3 imaging"],"tldr":"A drug that attacks small-cell lung cancer through a protein called DLL3 is already approved, but there is no approved scan that shows whether a patient's tumours still carry that protein. Doctors decide from a single biopsy taken from one place, which cannot show what the rest of the disease is doing.","summary":"Tarlatamab, a DLL3-directed bispecific T-cell engager, received accelerated FDA approval on 16 May 2024 and traditional approval on 19 November 2025, and DLL3-directed antibody-drug conjugates, CAR-T cells and a second T-cell engager (obrixtamig) are in trials. Patient selection rests on tissue immunohistochemistry from one archival or fresh biopsy. DLL3 is expressed in 85% of small-cell lung cancers at a 25% cut-off in the largest real-world series (895 of 1,050 patients), so most patients qualify on a single sample, but nothing in routine practice shows whether every metastatic site still expresses the target.\n\nOne imaging agent has human data. The zirconium-89-labelled anti-DLL3 antibody 89Zr-DFO-SC16.56, run investigator-initiated at Memorial Sloan Kettering under NCT04199741, was reported in Lancet Oncology in 2024: 18 patients, DLL3-avid tumours delineated on a single scan in 12 of 15 patients in the expansion cohort, uptake congruent with DLL3 immunohistochemistry in 15 of 16 patients with evaluable tissue, mean effective dose 0.49 mSv/MBq, one grade 1 allergic reaction and no grade 2 or worse adverse events. The trial is still recruiting with an estimated 105 patients. A gallium-68 DLL3 tracer opened in China in May 2026 (NCT07677787, 20 patients planned) and has not reported. A next-generation MSK construct, 89Zr-DFO-TDI-Y-010, with a lutetium-177 therapeutic pair, is preclinical.\n\nThe gap is therefore not biological plausibility, which a published 94% concordance with immunohistochemistry supports, but the absence of any industry-sponsored development path: the only clinical agent is an academic antibody with multi-day imaging kinetics, and no DLL3 imaging agent has been filed with any regulator.","asOf":"2026-09-23","links":[{"label":"First-in-human DLL3 immuno-PET, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/"},{"label":"NCT04199741: 89Zr-DFO-SC16.56 immuno-PET of neuroendocrine tumours","url":"https://clinicaltrials.gov/study/NCT04199741"},{"label":"NCT07677787: DLL3-targeted PET/CT in small-cell lung cancer (gallium-68)","url":"https://clinicaltrials.gov/study/NCT07677787"},{"label":"DLL3 expression in 1,050 patients, Lung Cancer 2020","url":"https://pubmed.ncbi.nlm.nih.gov/32745892/"},{"label":"FDA: accelerated approval of tarlatamab, May 2024","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-extensive-stage-small-cell-lung-cancer"}],"tags":["theranostic gap","companion diagnostic","lung","neuroendocrine"],"related":["zr-89","ga-68","lu-177"],"indications":["sclc"],"sections":[],"technologies":["immuno-pet","pet-ct"],"targets":["dll3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"theranostic-gap","unmetNeed":"Before starting a DLL3-directed T-cell engager, no test shows whether every metastatic site in a patient with small-cell lung cancer still expresses DLL3, or whether some lesions have lost it; the decision rests on one biopsy from one place.","useCase":"A medical oncologist or nuclear medicine physician would scan a patient with extensive-stage small-cell lung cancer, or a patient with suspected neuroendocrine transformation of a lung or prostate adenocarcinoma, before committing to a DLL3-directed therapy. A whole-body map of DLL3-avid and DLL3-negative disease would either confirm the target or redirect the patient to another line, and would give a baseline for judging loss of target at progression.","hypothesis":"A same-day DLL3 imaging agent, built on a small molecule, peptide or antibody fragment rather than a full antibody, would agree with tissue immunohistochemistry at least as well as the published antibody tracer while capturing between-lesion heterogeneity that a single biopsy misses, and would identify the minority of patients whose disease has lost DLL3 before they are exposed to a T-cell engager.","rationale":"The published first-in-human antibody data already show target-specific uptake that tracks immunohistochemistry in 15 of 16 evaluable patients, so the target is reachable in vivo. DLL3 is expressed in the large majority of small-cell lung cancers but not uniformly, and DLL3-directed therapy carries a cytokine-release and neurotoxicity burden that makes treating a target-negative patient costly. The limitation of the existing agent is pharmacokinetic rather than biological: a zirconium-89 antibody requires imaging three to six days after injection, which no routine oncology service can absorb at scale.","test":"A prospective study of a same-day DLL3 tracer in patients starting a DLL3-directed T-cell engager, powered on the agreement between scan-positive and immunohistochemistry-positive disease on a per-lesion basis with biopsy as the truth standard in accessible lesions, and reporting how often the scan finds a target-negative lesion in a patient whose biopsy was target-positive. The response rate of scan-positive against scan-negative patients would be the secondary endpoint that decides whether the scan should gate treatment.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"89Zr-DFO-SC16.56, an academic anti-DLL3 antibody tracer at Memorial Sloan Kettering, phase 1/2 and still recruiting under NCT04199741, with 18 patients published in Lancet Oncology in 2024.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"DLL3 is expressed in 895 of 1,050 small-cell lung cancers (85%) at a 25% tumour-cell cut-off, and in 68% at a 75% cut-off, in the largest international real-world immunohistochemistry series.","source":"Rojo et al., Lung Cancer 2020;147:237-243","url":"https://pubmed.ncbi.nlm.nih.gov/32745892/","weighted":true},{"domain":"clinical-evidence","state":"thin","why":"One published first-in-human cohort of 18 patients with an antibody tracer; the trial continues to an estimated 105 patients. No second agent has reported human data.","source":"Tendler et al., Lancet Oncology 2024;25:1015-1024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/"},{"domain":"diagnostic-performance","state":"moderate","why":"A single scan delineated DLL3-avid tumour in 12 of 15 patients, and uptake agreed with tissue immunohistochemistry in 15 of 16 patients with evaluable tissue. No study yet relates scan findings to response on DLL3-directed therapy.","source":"Tendler et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/","weighted":true},{"domain":"safety-dosimetry","state":"moderate","why":"Mean effective dose 0.49 mSv/MBq with the highest absorbed organ dose in liver at 1.83 mGy/MBq; one grade 1 allergic reaction in 18 patients and no grade 2 or worse events.","source":"Tendler et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/"},{"domain":"regulatory-path","state":"thin","why":"No DLL3 imaging agent has been filed anywhere. The nearest precedent for a receptor-status tracer is 68Ga-DOTATATE, approved in 2016 on localisation performance against a reference standard rather than an outcome endpoint.","source":"NETSPOT FDA label","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208547lbl.pdf"}],"flags":[{"category":"technical","flag":"amber","why":"The only clinical agent is a full antibody needing imaging three to six days after injection, which does not fit a routine service. A same-day construct exists only preclinically."},{"category":"unmet-need","flag":"amber","why":"Real but narrow: because DLL3 is expressed in most small-cell lung cancers, a scan changes management mainly in the minority with heterogeneous or lost expression, and that fraction has not been measured prospectively."},{"category":"ip","flag":"amber","why":"The lead antibody and its next-generation successor are institutionally owned at Memorial Sloan Kettering; freedom to operate for an independent construct is unexamined in public sources."},{"category":"commercial","flag":"red","why":"Sales would depend on the DLL3 therapy market, and small-cell lung cancer is a small, short-lived population with no standalone diagnostic question of its own."},{"category":"isotope","flag":"green","why":"Any of gallium-68, fluorine-18 or copper-64 would suit a small-molecule or fragment construct; the published antibody uses zirconium-89, which is cyclotron-made but established."},{"category":"competition","flag":"green","why":"Only one academic agent has human data and one Chinese tracer has just opened; no company has a disclosed clinical DLL3 imaging programme."}],"competition":[{"name":"Memorial Sloan Kettering Cancer Center","what":"89Zr-DFO-SC16.56, the only DLL3 tracer with published human data, and a preclinical successor pair 89Zr-DFO-TDI-Y-010 with 177Lu therapy.","stage":"phase 1/2 recruiting","url":"https://clinicaltrials.gov/study/NCT04199741"},{"name":"First Affiliated Hospital of Xiamen University","what":"A gallium-68 DLL3-targeted PET tracer; 20 patients planned, opened May 2026, no results published.","stage":"recruiting","url":"https://clinicaltrials.gov/study/NCT07677787"},{"name":"Amgen","what":"Tarlatamab, the approved DLL3 T-cell engager that creates the demand; selection is by tissue immunohistochemistry, not imaging.","stage":"approved","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-extensive-stage-small-cell-lung-cancer"},{"name":"Boehringer Ingelheim","what":"Obrixtamig, a second DLL3 T-cell engager in DLL3-positive small-cell lung cancer and other neuroendocrine tumours.","stage":"active, not recruiting","url":"https://clinicaltrials.gov/study/NCT04429087"}],"differentiation":"The competing test is DLL3 immunohistochemistry on tissue, which is already used to enrol patients in trials. No blood or ctDNA test for DLL3 status exists. Imaging would add whole-body coverage and repeatability rather than a new biological readout, which is exactly why its value depends on how often lesions within one patient disagree.","metrics":[{"label":"Small-cell lung cancers expressing DLL3 in at least 25% of tumour cells","value":"85%","source":"Rojo et al., Lung Cancer 2020 (895 of 1,050)","url":"https://pubmed.ncbi.nlm.nih.gov/32745892/"},{"label":"Patients in whom one scan delineated DLL3-avid tumour","value":"12 of 15","source":"Tendler et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/"},{"label":"Agreement between tracer uptake and tissue immunohistochemistry","value":"15 of 16","source":"Tendler et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38950555/"}],"risks":["If almost every patient is DLL3-positive on biopsy, a scan that confirms it adds cost without changing management; the case rests on heterogeneity that has not been quantified prospectively.","The market is tied to one therapy class in one small indication, so a companion-only agent carries the therapy's commercial risk without any standalone use to fall back on.","A full antibody cannot be delivered at service scale; whoever wants this needs a same-day construct, and the published work does not provide one."],"watch":["Readout of the expansion cohort of NCT04199741, which would take the published series from 18 to a larger number of patients.","First results from the gallium-68 DLL3 tracer at Xiamen (NCT07677787), the first non-antibody agent in humans.","Any registered trial of the MSK next-generation 89Zr-DFO-TDI-Y-010 or its lutetium-177 pair, which would signal the field moving to a theranostic construct."],"route":"/opportunities/opp-dll3-imaging-sclc/"}
{"id":"opp-nectin4-imaging-urothelial","kind":"opportunity","name":"A liver-cleared Nectin-4 tracer for urothelial cancer","aka":["Nectin-4 PET","nectin-4 imaging"],"tldr":"An approved bladder cancer drug works by latching onto a protein called Nectin-4, and half of patients lose that protein as the disease spreads. The one scan built to show it is cleared through the kidneys, so the bladder and the nearby lymph nodes glow with waste tracer and are the hardest places to read.","summary":"Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, has been approved since December 2019 and now reaches into the perioperative setting: in November 2025 the FDA approved pembrolizumab with enfortumab vedotin as neoadjuvant then adjuvant treatment for cisplatin-ineligible muscle-invasive bladder cancer, on a trial of 344 patients that reported a hazard ratio of 0.40 for recurrence, progression or death. Selection does not require a Nectin-4 assay, yet Nectin-4 expression falls in more than half of cases during metastatic progression and more than a third of metastases are Nectin-4-negative.\n\nThe imaging work is almost entirely Chinese and academic. The bicyclic peptide tracer 68Ga-N188, from Peking University, has a published first-in-human study in 14 patients with advanced urothelial cancer plus two healthy volunteers, and a 62-patient head-to-head study against FDG across 16 tumour types. It is registered in three Chinese trials. Its published limitation is decisive for the indication that matters most: the tracer is excreted in urine, and a 2025 review states plainly that this poses challenges for in-situ bladder cancer detection because of high background activity in the urinary tract.\n\nSo the opportunity is not a target in search of a tracer, nor a tracer in search of a target, but a pharmacokinetic specification: a Nectin-4 ligand cleared hepatobiliary rather than renally, which could read the bladder wall and the pelvic nodes where staging and surgical decisions are actually made.","asOf":"2026-09-23","links":[{"label":"68Ga-N188 first-in-human, Clinical Cancer Research 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37093191/"},{"label":"68Ga-N188 against FDG in 62 patients, Journal of Nuclear Medicine 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38719240/"},{"label":"Review noting urinary excretion as a barrier to in-situ bladder detection, 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12227459/"},{"label":"Nectin-4 expression and loss in metastatic progression, Clinical Cancer Research 2023","url":"https://aacrjournals.org/clincancerres/article/29/8/1496/725070/Membranous-NECTIN-4-Expression-Frequently"},{"label":"FDA: perioperative enfortumab vedotin plus pembrolizumab, November 2025","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer"}],"tags":["theranostic gap","bladder","clearance","pelvic staging"],"related":["ga-68","f-18"],"indications":["urothelial-cancer"],"sections":[],"technologies":["pet-ct","peptide-drug-conjugate"],"targets":["nectin4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"theranostic-gap","unmetNeed":"Before radical cystectomy or before starting enfortumab vedotin, no test shows whether the bladder tumour and the pelvic nodes still express Nectin-4, because the only human Nectin-4 tracer is renally excreted and urinary activity obscures exactly that region.","useCase":"A urologist and a nuclear medicine physician would use it twice: to stage the pelvis before cystectomy, where CT nodal staging is weak, and to confirm target expression across metastatic sites before committing a patient to an antibody-drug conjugate with a real toxicity burden. A hepatobiliary-cleared tracer would make the bladder wall and pelvic nodes readable on the same scan.","hypothesis":"A Nectin-4-binding peptide or small molecule engineered for hepatobiliary clearance will image the primary bladder tumour and pelvic nodes that the renally excreted 68Ga-N188 cannot, and will detect the loss of Nectin-4 in metastatic disease that a single biopsy misses.","rationale":"Nectin-4 is expressed in 83 to 97% of bladder cancers depending on the series and antibody used, and 68Ga-N188 has already shown that the target is reachable with a bicyclic peptide in humans. Loss of expression during metastatic progression is documented in more than half of cases, with over a third of metastases negative, and NECTIN4 amplification has been proposed as a more stable predictor of enfortumab vedotin benefit than protein staining. The failure mode of the existing tracer is excretion route, not affinity, and clearance can be engineered: the same problem was solved for other peptide classes by changing linker charge and lipophilicity.","test":"A first-in-human study of a hepatobiliary-cleared Nectin-4 ligand in patients scheduled for radical cystectomy with pelvic lymph node dissection, with node-by-node histopathology as the truth standard, reporting sensitivity and specificity for pelvic nodal metastasis and, as a co-primary, the readability of the bladder wall against the published renally excreted comparator.","maturity":"early-clinical","verdict":"standalone-and-companion","mostAdvanced":"68Ga-N188, a bicyclic peptide tracer from Peking University Cancer Hospital, with two published human studies (14 patients, then 62 across 16 tumour types) and three registered Chinese trials, but renal excretion that limits pelvic reading.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"Nectin-4 is reported in 83% of 524 bladder cancers by tissue microarray and over 97% in another series, against 67% in upper-tract disease; expression falls in more than 50% of cases during metastatic progression, with over a third of metastases negative.","source":"Klumper et al., Clinical Cancer Research 2023; Hoffman-Censits review","url":"https://aacrjournals.org/clincancerres/article/29/8/1496/725070/Membranous-NECTIN-4-Expression-Frequently","weighted":true},{"domain":"clinical-evidence","state":"moderate","why":"68Ga-N188 has a published first-in-human study of 14 patients with advanced urothelial cancer and a 62-patient head-to-head study against FDG, all single-country and academic.","source":"Duan et al., Clinical Cancer Research 2023; Zhang et al., J Nucl Med 2024","url":"https://pubmed.ncbi.nlm.nih.gov/37093191/"},{"domain":"diagnostic-performance","state":"thin","why":"No study reports sensitivity or specificity against nodal histopathology, and the published review states that urinary excretion challenges in-situ bladder detection because of urinary-tract background.","source":"Speltri, Badrane et al., Molecular Diagnosis and Therapy 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12227459/","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No adverse events are reported in the published first-in-human cohorts, but the series are small and no formal dosimetry figure for a pelvis-readable construct exists because no such construct has been made.","source":"Duan et al., Clinical Cancer Research 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37093191/"},{"domain":"regulatory-path","state":"moderate","why":"No Nectin-4 imaging agent has any filing anywhere, but 68Ga-PSMA-11 set the precedent for a pelvic-nodal claim: its initial-staging trial used sensitivity and specificity for pelvic nodal metastases against prostatectomy pathology as the primary endpoint.","source":"FDA multidiscipline review, 68Ga-PSMA-11","url":"https://jnm.snmjournals.org/content/62/2/146"}],"flags":[{"category":"technical","flag":"red","why":"The known human tracer is renally excreted and its own literature says this obstructs in-situ bladder detection; the opportunity requires re-engineering clearance, which is unproven for this ligand class."},{"category":"unmet-need","flag":"green","why":"Nodal staging before cystectomy is weak on CT and target loss in metastatic disease is documented in over half of cases, so both the staging and the selection question are live."},{"category":"ip","flag":"amber","why":"The bicyclic peptide scaffold behind 68Ga-N188 derives from a therapeutic programme, and the leading published work sits with Chinese academic centres; freedom to operate for a new clearance-engineered ligand is unexamined in public sources."},{"category":"commercial","flag":"green","why":"A pelvis-readable tracer has a staging use of its own in muscle-invasive disease as well as a selection use alongside an approved antibody-drug conjugate now moving into perioperative treatment."},{"category":"isotope","flag":"green","why":"Gallium-68 already works for the peptide, and a fluorine-18 version would suit distribution."},{"category":"competition","flag":"amber","why":"Three registered Chinese trials of 68Ga-N188 are running and the field is publishing quickly, but nobody has disclosed a hepatobiliary-cleared construct."}],"competition":[{"name":"Peking University Cancer Hospital and Peking University First Hospital","what":"68Ga-N188, the only Nectin-4 tracer with published human data; three registered trials (NCT05321316, NCT05593107, NCT06648317).","stage":"early clinical","url":"https://pubmed.ncbi.nlm.nih.gov/37093191/"},{"name":"Astellas and Pfizer","what":"Enfortumab vedotin, the approved Nectin-4 antibody-drug conjugate that creates the selection question; no Nectin-4 assay is required on the label.","stage":"approved","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer"},{"name":"Mayo Clinic Laboratories","what":"A commercially available Nectin-4 immunohistochemistry assay reporting percent positive cells and H-score, the incumbent test.","stage":"in clinical use","url":"https://www.mayocliniclabs.com/test-catalog/Overview/622259"}],"differentiation":"Nectin-4 immunohistochemistry is already purchasable and NECTIN4 amplification by FISH has been proposed as a more stable predictor of benefit. Both need a biopsy of one lesion. No blood or ctDNA test for Nectin-4 status was found. Imaging earns its place only where the answer differs between lesions, or where the lesion in question is a pelvic node nobody wants to biopsy.","metrics":[{"label":"Bladder cancers positive for Nectin-4 by tissue microarray","value":"83% of 524","source":"Challita-Eid et al., cited in Hoffman-Censits review","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8429050/"},{"label":"Cases losing Nectin-4 expression during metastatic progression","value":"over 50%","source":"Klumper et al., Clinical Cancer Research 2023","url":"https://aacrjournals.org/clincancerres/article/29/8/1496/725070/Membranous-NECTIN-4-Expression-Frequently"},{"label":"Reduction in risk of recurrence, progression or death with perioperative enfortumab vedotin plus pembrolizumab","value":"HR 0.40","source":"EV-303/KEYNOTE-905, 344 patients, FDA approval November 2025","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer"}],"risks":["Clearance engineering may not survive contact with affinity: a hepatobiliary-cleared analogue could lose the binding that makes the peptide work.","Hepatic background could simply move the problem, since the liver is a common site of urothelial metastasis.","If NECTIN4 amplification on tissue turns out to predict benefit reliably, the selection half of the case weakens and only the staging use remains."],"watch":["Results from the three registered 68Ga-N188 trials, particularly any per-lesion comparison against nodal pathology.","Any published Nectin-4 ligand with a hepatobiliary clearance profile, which would be the first direct competitor for this specification.","Whether the perioperative approval shifts practice toward pre-cystectomy target confirmation, which is where a readable pelvis pays."],"route":"/opportunities/opp-nectin4-imaging-urothelial/"}
{"id":"opp-ceacam5-imaging-colorectal","kind":"opportunity","name":"CEACAM5 imaging for occult colorectal recurrence","aka":["CEA PET","CEACAM5 PET"],"tldr":"After bowel cancer surgery, a rising blood marker often signals that the cancer is back, but scans frequently cannot say where. The one scan ever approved for that exact problem was withdrawn from the market in 2005 and nothing has replaced it.","summary":"The clinical scenario is specific and common: a treated colorectal cancer patient's serum CEA rises during surveillance while CT, MRI and colonoscopy are normal or equivocal. Salvage surgery or ablation can still cure oligometastatic recurrence, but only if the disease can be localised. Arcitumomab (CEA-Scan), a technetium-99m anti-CEA antibody fragment approved for precisely this indication, was withdrawn from both the US and EU markets in 2005; clinicians now fall back on FDG PET/CT off-label, which in one referred series found recurrence in 56 of 88 such patients.\n\nMeanwhile the therapeutic side of CEACAM5 has grown: antibody-drug conjugates, T-cell engagers and CAR-T programmes target it, and the field has learned that CEA-directed therapy selection is not the same question as CEA-directed localisation. The most advanced CEACAM5-directed imaging agent in humans is not a PET tracer at all but SGM-101, a near-infrared fluorescent anti-CEA antibody for intraoperative use, now in a randomised phase 3 trial (NCT03659448, about 300 patients). For PET, the most advanced is the CEA-targeted nanobody 68Ga-HNI01 at first-in-human scale, nine patients.\n\nThe competitive picture changed independently of imaging. Tumour-informed ctDNA now detects recurrence a median of 5.9 months before radiological recurrence in GALAXY/CIRCULATE-Japan, and ctDNA-guided adjuvant therapy was non-inferior to standard management in DYNAMIC while halving chemotherapy use. ctDNA says whether and roughly when; it does not say where. That distinction is the whole of the case for a CEACAM5 tracer, and it is a stronger case now than when CEA-Scan was withdrawn, because more patients are being flagged as molecularly positive with nothing to localise.","asOf":"2026-09-23","links":[{"label":"FDG PET/CT for occult colorectal recurrence with raised CEA","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5153343/"},{"label":"NCT03659448: SGM-101 phase 3 in colorectal cancer","url":"https://clinicaltrials.gov/study/NCT03659448"},{"label":"GALAXY: ctDNA lead time over radiological recurrence, Nature Medicine 2024","url":"https://www.nature.com/articles/s41591-024-03254-6"},{"label":"DYNAMIC: ctDNA-guided adjuvant therapy in stage II colon cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9701133/"},{"label":"CT nodal staging accuracy meta-analysis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13394594/"}],"tags":["unmet need first","colorectal","recurrence","ctDNA"],"related":["ga-68","f-18","tc-99m"],"indications":["colorectal-cancer"],"sections":[],"technologies":["immuno-pet","pet-ct","fdg-pet"],"targets":["ceacam5"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"When serum CEA or a ctDNA assay says a treated colorectal cancer has recurred but CT, MRI and colonoscopy cannot find it, no approved molecular imaging agent localises the disease well enough to plan salvage surgery.","useCase":"A colorectal multidisciplinary team would scan the patient whose CEA or ctDNA has turned positive with negative conventional imaging, to find and localise resectable recurrence, and would also use it for peritoneal and nodal mapping before an attempted curative resection. The output that matters is a lesion a surgeon can go to.","hypothesis":"A CEACAM5-specific PET agent will localise recurrent colorectal cancer in patients with rising CEA or detectable ctDNA and negative conventional imaging at a higher rate and with fewer false positives than FDG PET/CT, because it reports a lineage-specific antigen rather than glucose metabolism shared with inflammation.","rationale":"The target is expressed in the large majority of colorectal adenocarcinomas and the approach has regulatory precedent: an anti-CEA imaging agent was once approved for this indication. FDG PET/CT already works well enough in this setting to be used off-label, which establishes both that the clinical question is real and that the bar for a specific agent is a meaningful improvement over FDG rather than over nothing. The population being referred for localisation is growing because ctDNA surveillance flags molecular recurrence months before imaging, and antibody fragments and nanobodies now give same-day kinetics that arcitumomab's generation could not.","test":"A prospective study in patients with rising CEA or positive tumour-informed ctDNA and negative conventional imaging, comparing a CEACAM5 PET agent head to head with FDG PET/CT in the same patients, with histopathology or 12-month follow-up as the truth standard, and reporting the proportion of patients in whom the scan identified a resectable lesion that changed management.","maturity":"early-clinical","verdict":"standalone-and-companion","mostAdvanced":"SGM-101, a fluorescent anti-CEA antibody for intraoperative use from Surgimab, in a randomised phase 3 trial of about 300 patients; for PET specifically, the nanobody 68Ga-HNI01 at nine patients.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"CEACAM5 is a long-established colorectal lineage antigen; serum CEA is in every surveillance guideline, and an anti-CEA imaging agent was once approved for occult recurrence, so in-vivo targeting is proven in principle.","source":"Arcitumomab regulatory history","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5153343/"},{"domain":"clinical-evidence","state":"thin","why":"No CEACAM5 PET agent has gone beyond first-in-human; the nanobody 68Ga-HNI01 has nine patients. The only phase 3 CEA-directed imaging agent is a fluorescence agent for use in the operating theatre, not a tracer.","source":"NCT03659448 and first-in-human nanobody report","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7892528/"},{"domain":"diagnostic-performance","state":"moderate","why":"The incumbent, FDG PET/CT, detected recurrence in 56 of 88 patients referred with raised CEA and negative conventional imaging, so any new agent must beat a working off-label comparator rather than fill a void.","source":"FDG PET/CT in occult colorectal recurrence","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5153343/","weighted":true},{"domain":"safety-dosimetry","state":"none","why":"No published dosimetry for a current-generation CEACAM5 PET agent at a scale worth quoting; the withdrawn technetium-99m fragment is not a guide to a gallium-68 or fluorine-18 construct."},{"domain":"regulatory-path","state":"moderate","why":"A direct precedent exists in the same indication, which is unusual: arcitumomab was approved for occult colorectal recurrence before being withdrawn in 2005, so the endpoint and claim structure have been accepted once.","source":"Arcitumomab history","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5153343/","weighted":true}],"flags":[{"category":"technical","flag":"amber","why":"Bowel and liver background is the hard part of abdominal imaging, and the antigen is shed into serum, which can blunt tumour uptake; a fragment or nanobody format is probably required."},{"category":"unmet-need","flag":"green","why":"A defined, guideline-recognised scenario with no approved agent since 2005, and a population growing because ctDNA surveillance flags recurrence earlier than imaging can localise it."},{"category":"ip","flag":"amber","why":"CEA binders are a crowded, decades-old space with many antibodies and fragments in therapeutic programmes; novelty would have to come from format and chelation rather than the binding site."},{"category":"commercial","flag":"amber","why":"The localisation use stands alone, but the scan is a one-off per recurrence episode in a surveillance population, so volume depends on how widely ctDNA surveillance is adopted."},{"category":"isotope","flag":"green","why":"Gallium-68 or fluorine-18 on a fragment gives same-day imaging; no supply constraint."},{"category":"competition","flag":"green","why":"No company has a disclosed late-stage CEACAM5 PET programme; the phase 3 activity is in fluorescence-guided surgery, which is complementary rather than competing."}],"competition":[{"name":"Surgimab","what":"SGM-101, a fluorescent anti-CEA antibody for intraoperative delineation of colorectal and peritoneal disease, in a randomised phase 3 trial of about 300 patients.","stage":"phase 3","url":"https://clinicaltrials.gov/study/NCT03659448"},{"name":"Academic nanobody programmes","what":"68Ga-HNI01, a CEA-targeted nanobody, first-in-human at nine patients.","stage":"phase 1","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7892528/"},{"name":"ctDNA surveillance (Natera and others)","what":"Tumour-informed ctDNA detects recurrence a median of 5.91 months before radiological recurrence in GALAXY, creating the patients who need localising.","stage":"in clinical use","url":"https://www.nature.com/articles/s41591-024-03254-6"}],"differentiation":"Serum CEA misses up to 70% of recurrences and ctDNA says whether and when but not where: a positive ctDNA result with negative imaging is a management dilemma, not an answer. A CEACAM5 tracer competes with FDG PET/CT, not with the blood tests, and its case is specificity in an abdomen full of physiological FDG uptake.","metrics":[{"label":"Recurrences detected by FDG PET/CT in patients with raised CEA and negative conventional imaging","value":"56 of 88","source":"Occult recurrence series","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5153343/"},{"label":"Lead time of tumour-informed ctDNA over radiological recurrence","value":"5.91 months median","source":"GALAXY, Nature Medicine 2024","url":"https://www.nature.com/articles/s41591-024-03254-6"},{"label":"Pooled sensitivity and specificity of CT for nodal staging in colorectal cancer","value":"69% and 66%","source":"Meta-analysis of 29 studies, 5,634 people","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13394594/"},{"label":"Colorectal recurrences that occur without CEA elevation","value":"up to 70%","source":"Permanente Journal review","url":"https://www.thepermanentejournal.org/doi/10.7812/TPP/18-022"}],"risks":["FDG PET/CT is already good enough in this scenario for many teams, so the margin a specific agent must beat is not zero.","Shed circulating CEA can compete with tumour binding and blunt contrast, which is a formulation and format problem rather than a target problem.","If ctDNA-guided management moves toward treating molecular recurrence systemically without localising it, the surgical rationale for a localising scan narrows."],"watch":["The randomised SGM-101 phase 3 readout, which will show whether CEA-directed imaging changes surgical outcomes at all, in any modality.","Any CEACAM5 PET agent entering a trial with rising CEA or ctDNA positivity as the enrolment criterion rather than known measurable disease.","Guideline language on what to do with a positive ctDNA and a negative scan, which is where the demand for this agent will be written down."],"route":"/opportunities/opp-ceacam5-imaging-colorectal/"}
{"id":"opp-her3-imaging-crossover","kind":"opportunity","name":"HER3 imaging, and why three tracers stalled","aka":["HER3 PET"],"tldr":"HER3 sits on most lung cancers and there are drugs aimed at it, so a scan showing which tumours carry it looks obvious. Three attempts were made and all three stopped, largely because the drug's own trials could not show that how much HER3 a tumour has predicts whether the drug works.","summary":"HER3 is the textbook crossover case: expressed in around 80% of non-small cell lung cancers, targeted by patritumab deruxtecan and other antibody-drug conjugates, with no radioligand in routine use. Three antibody PET tracers were built (64Cu-patritumab, 89Zr-GSK2849330, 89Zr-lumretuzumab) and all three belong to drug programmes that lost momentum or were discontinued. Only one HER3 imaging trial is currently recruiting: 89Zr-patritumab deruxtecan at the Netherlands Cancer Institute with Daiichi Sankyo as collaborator, 16 patients, on the explicit rationale that HER3 expression can be assessed non-invasively including at sites that are difficult to biopsy.\n\nThe honest problem is not the tracer. Patritumab deruxtecan's own biomarker analyses report no relationship between efficacy and HER3 protein expression by immunohistochemistry, and the SOLTI TOT-HER3 work found activity across a wide range of ERBB3 mRNA and HER3 protein levels, suggesting limited predictive value. One published tracer study could determine no correlation between tumour uptake and ex-vivo immunohistochemistry. The drug itself received a complete response letter in June 2024 on a third-party manufacturing finding, and the BLA was withdrawn in May 2025 after HERTHENA-Lung02 missed its overall survival endpoint.\n\nThis record exists as a worked negative: the crossover lens will keep producing targets like this, and the discipline it needs is to ask whether expression predicts benefit before assuming a companion diagnostic has a market.","asOf":"2026-09-23","links":[{"label":"NCT06222489: 89Zr-patritumab deruxtecan PET/CT","url":"https://clinicaltrials.gov/study/NCT06222489"},{"label":"No relationship between HER3-DXd efficacy and HER3 immunohistochemistry, Nature Communications 2024","url":"https://www.nature.com/articles/s41467-024-50056-y"},{"label":"Complete response letter for patritumab deruxtecan, June 2024","url":"https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer"},{"label":"No validated HER3 immunohistochemistry assays or thresholds (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12758208/"},{"label":"Fluoroestradiol F-18 label, the receptor-imaging precedent","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212155s000lbl.pdf"}],"tags":["target crossover","worked negative","lung","companion diagnostic"],"related":["zr-89","cu-64"],"indications":["nsclc"],"sections":[],"technologies":["immuno-pet","pet-ct"],"targets":["her3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"target-crossover","unmetNeed":"There is no non-invasive way to measure HER3 across all of a patient's disease, including its rise after EGFR-inhibitor therapy, but it is also not established that knowing HER3 expression changes who benefits from a HER3-directed drug.","useCase":"In its plausible form, a HER3 tracer is a pharmacodynamic and trial-enrichment tool rather than a clinical test: measuring target engagement and the change in HER3 after EGFR-inhibitor therapy inside a drug-development programme. A clinical selection use would require a predictive relationship that the drug's own trials have so far failed to demonstrate.","hypothesis":"Whole-body HER3 quantification will predict response to a HER3-directed antibody-drug conjugate where single-site immunohistochemistry does not, because the failure of tissue testing reflects sampling and assay variability rather than the absence of a true dose-response relationship.","rationale":"HER3 is expressed in the great majority of lung cancers and rises after EGFR-inhibitor treatment, so there is a real biological signal to measure, and imaging is the only way to measure it everywhere at once. Against that, the published record is discouraging in a specific and informative way: there are no validated HER3 immunohistochemistry assays and no standardised scoring thresholds, the sponsor found no relationship between expression and efficacy, and one tracer study could not correlate uptake with tissue staining. The hypothesis above is testable but currently unsupported.","test":"A trial-embedded study in patients receiving a HER3-directed antibody-drug conjugate, imaging before treatment and after one cycle, powered to relate baseline tracer uptake and its change to objective response. The question it must answer is not whether the tracer binds HER3 but whether tracer uptake separates responders from non-responders where immunohistochemistry did not.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"89Zr-patritumab deruxtecan PET/CT at the Netherlands Cancer Institute with Daiichi Sankyo, 16 patients, recruiting under NCT06222489; the only active HER3 imaging trial found.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"HER3 has been reported in 83% of non-small cell lung cancers and estimated at up to 80% depending on stage; overexpression occurred in 42% of a 45-patient cohort, more often than HER2.","source":"Published NSCLC series","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"},{"domain":"clinical-evidence","state":"thin","why":"Three antibody tracers were built and all sit in stalled or discontinued drug programmes; one active trial of 16 patients is recruiting. No imaging agent has reported a relationship to outcome.","source":"NCT06222489","url":"https://clinicaltrials.gov/study/NCT06222489"},{"domain":"diagnostic-performance","state":"none","why":"For 64Cu-patritumab, no correlation between tumour uptake and ex-vivo immunohistochemistry could be determined, and the drug's own analyses report no relationship between HER3 protein expression and efficacy.","source":"Sponsor biomarker analyses and tracer report","url":"https://www.nature.com/articles/s41467-024-50056-y","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"Antibody-based HER3 tracers have been given to humans without reported safety signals in small series, but no dosimetry figure worth quoting has been published for the current agent."},{"domain":"regulatory-path","state":"moderate","why":"Receptor-status PET has a precedent: fluoroestradiol F-18 was approved in May 2020 as an adjunct to biopsy for detecting oestrogen-receptor-positive lesions, judged on reader concordance against biopsy rather than a drug-selection claim.","source":"FDA review, fluoroestradiol F-18","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212155s000lbl.pdf"}],"flags":[{"category":"technical","flag":"amber","why":"Antibody kinetics again: the only active agent is a zirconium-89 labelled antibody-drug conjugate, which images days after injection."},{"category":"unmet-need","flag":"red","why":"The clinical need is unproven, not merely unmet: the sponsor's own trials found no relationship between HER3 expression and benefit, so a test that measures expression may change nothing."},{"category":"ip","flag":"red","why":"Every clinical HER3 tracer is derived from a specific therapeutic antibody owned by its sponsor, so an independent programme would need a new binder."},{"category":"commercial","flag":"red","why":"Companion-only, and the lead therapy's BLA was withdrawn in May 2025 after a failed overall-survival endpoint, so the market it would serve is not currently approved."},{"category":"isotope","flag":"amber","why":"Zirconium-89 and copper-64 are available but cyclotron-dependent and less widely distributed than gallium-68 or fluorine-18."},{"category":"competition","flag":"green","why":"Nobody is competing, which in this case reflects the weak predictive case rather than an opening."}],"competition":[{"name":"Netherlands Cancer Institute with Daiichi Sankyo","what":"89Zr-patritumab deruxtecan PET/CT, 16 patients, recruiting; the only active HER3 imaging trial found.","stage":"recruiting","url":"https://clinicaltrials.gov/study/NCT06222489"},{"name":"Historical programmes","what":"64Cu-patritumab, 89Zr-GSK2849330 and 89Zr-lumretuzumab, all attached to drug programmes that were discontinued or lost momentum.","stage":"discontinued","url":"https://apps.dtic.mil/sti/pdfs/AD1050824.pdf"}],"differentiation":"HER3 immunohistochemistry exists but is unvalidated: reviews state there are no validated assays and no standardised scoring thresholds for predicting benefit, and an mRNA alternative developed by the SOLTI group was also not predictive. Imaging would differ by sampling every lesion, but it inherits the underlying problem that no measure of HER3 has yet predicted response.","metrics":[{"label":"Non-small cell lung cancers reported to express HER3","value":"83%","source":"Published NSCLC series","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"},{"label":"Patients randomised in HERTHENA-Lung02, whose overall-survival miss preceded BLA withdrawal","value":"586","source":"HERTHENA-Lung02 reporting","url":"https://www.nature.com/articles/s41467-024-50056-y"}],"risks":["The predictive premise may simply be false: if HER3 level does not determine benefit, no measurement of it will.","The tracer is tied to a therapeutic asset whose regulatory path has already failed once.","Antibody format and isotope choice make routine delivery expensive relative to the information gained."],"watch":["Results from NCT06222489, especially any relationship between uptake and response rather than uptake and staining.","Whether any HER3 drug programme re-files and, if so, whether a selection biomarker appears on its label.","Publication of a validated, standardised HER3 tissue assay, which would either remove the need for imaging or give it a comparator worth beating."],"route":"/opportunities/opp-her3-imaging-crossover/"}
{"id":"opp-cldn18-2-imaging-gastric","kind":"opportunity","name":"Claudin-18.2 imaging when one biopsy says negative","aka":["CLDN18.2 PET","claudin 18.2 imaging"],"tldr":"Stomach cancer patients now get a drug only if a biopsy shows a protein called claudin-18.2. One biopsy core finds it only about six times in ten when the whole tumour has it, so patients are being refused a treatment on a test that misses.","summary":"Zolbetuximab is approved in the US, EU, Japan, China and elsewhere for CLDN18.2-positive, HER2-negative gastric and gastro-oesophageal junction adenocarcinoma, with patient selection by the VENTANA CLDN18 (43-14A) RxDx immunohistochemistry assay. Roughly 38% of screened patients in the pooled SPOTLIGHT and GLOW populations were positive at the 75%-of-tumour-cells threshold. In June 2026 China's regulator approved satricabtagene autoleucel, a CLDN18.2 CAR-T, in the same biomarker-defined population, so the number of decisions resting on this one assay is rising.\n\nThe assay's weakness is measurable. Against whole-tumour-section ground truth, a single representative biopsy gave 58.8% sensitivity for CLDN18.2, rising to 76.5% with six to eight biopsies, and a minimum of six endoscopic biopsies was needed to keep false negatives down; 18% of tumours were discordant between the primary and the matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate with 91% overall accuracy.\n\nThe imaging work is almost entirely Chinese and early: 68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L) each have a published pilot of 11 to 17 patients, and none has entered a multicentre or registration trial. The opportunity is therefore unusually well specified for a crossover case, because the incumbent test's failure rate is published and the decision it gates is binary.","asOf":"2026-09-23","links":[{"label":"Single-biopsy sensitivity for CLDN18.2, Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"CLDN18.2 positivity in pooled SPOTLIGHT and GLOW screening","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"First-in-human CLDN18.2 PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"label":"Multi-laboratory ring trial of CLDN18.2 immunohistochemistry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"Gastric cancer biomarker testing review, naming the approved assay","url":"https://www.cancerbiomed.org/content/22/3/212"}],"tags":["target crossover","gastric","companion diagnostic","sampling error"],"related":["ga-68","i-124"],"indications":["gastric-oesophageal-cancer"],"sections":[],"technologies":["immuno-pet","pet-ct"],"targets":["cldn18-2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"target-crossover","unmetNeed":"When a gastric cancer biopsy reads CLDN18.2-negative, no test distinguishes a truly negative tumour from a false negative caused by sampling, so patients may be denied an approved antibody or CAR-T on a result that a single core gets right only about six times in ten.","useCase":"A gastrointestinal oncologist would order the scan for the patient whose biopsy is CLDN18.2-negative or equivocal but whose clinical situation makes the drug worth having, and for the patient whose only accessible tissue is an old primary specimen while the disease now sits in nodes and peritoneum. A positive scan would justify re-biopsy or treatment; a negative scan across all disease would close the question.","hypothesis":"Whole-body CLDN18.2 imaging will identify patients whose single-biopsy immunohistochemistry is falsely negative, at a rate consistent with the published 12% laboratory false-negative rate and the 41% single-core miss rate, and will thereby qualify patients for approved CLDN18.2-directed therapy who are currently refused it.","rationale":"Three independent Chinese groups have shown that CLDN18.2 can be imaged in patients, and the target is a tight-junction protein whose accessibility in tumour tissue is what makes the therapeutic antibody work. The incumbent test's failure mode is documented with numbers, from both a whole-section comparison and a ring trial, and 18% primary-versus-node discordance is exactly the kind of error whole-body imaging addresses. Two approved therapies now depend on this selection step, one of them a CAR-T, which raises the cost of a false negative.","test":"A prospective study in patients with gastric or junctional adenocarcinoma enrolling on the basis of a CLDN18.2-negative or equivocal biopsy, imaging all patients and then taking a protocol-mandated multi-core re-biopsy of a scan-positive lesion, with the primary endpoint being the proportion of scan-positive patients whose re-biopsy is positive at the label threshold. That design directly measures the false-negative rescue rate the case rests on.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"Three Chinese first-in-human PET tracers (68Ga-PMD22, 68Ga-NC-BCH, 124I-18B10(10L)) with published pilots of 11 to 17 patients; none in a multicentre or registration trial.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"CLDN18.2 positivity at the 75% threshold was 38.4% across 4,507 patients screened for SPOTLIGHT and GLOW, and Astellas reports approximately 35% positivity in Chinese patients with advanced disease.","source":"Pooled screening analysis, Gastric Cancer 2024","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1","weighted":true},{"domain":"clinical-evidence","state":"thin","why":"Three separate first-in-human tracer studies of 11 to 17 patients each, all single-centre and all in China; no comparative or multicentre data.","source":"Published pilot studies","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"domain":"diagnostic-performance","state":"moderate","why":"The case is built on the incumbent's measured failure: 58.8% sensitivity from one representative biopsy against whole-section truth, 76.5% with six to eight biopsies, 18% primary-versus-node discordance, and a 12% false-negative rate in a multi-laboratory ring trial.","source":"Naujoks et al., Scientific Reports 2025; ring trial","url":"https://www.nature.com/articles/s41598-025-12337-4","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No adverse events reported in the small published cohorts; the iodine-124 construct carries a higher radiation burden than the gallium-68 ones, and no formal comparison has been published."},{"domain":"regulatory-path","state":"moderate","why":"An approved companion diagnostic already defines the claim: the VENTANA CLDN18 (43-14A) RxDx assay. An imaging agent would have to be positioned against it, most plausibly as an adjunct where tissue is inadequate rather than as a replacement.","source":"Gastric cancer biomarker review","url":"https://www.cancerbiomed.org/content/22/3/212"}],"flags":[{"category":"technical","flag":"amber","why":"Gastric wall and gastro-oesophageal junction imaging sits next to physiological uptake, and the published agents are antibody or antibody-fragment based with the kinetics that implies."},{"category":"unmet-need","flag":"green","why":"A binary treatment decision gated by a test with a published 12% laboratory false-negative rate and a 41% single-core miss rate against whole-section truth."},{"category":"ip","flag":"amber","why":"The binders come from therapeutic antibody programmes and the published imaging work sits with Chinese academic centres and their partners."},{"category":"commercial","flag":"amber","why":"Companion-only by construction, but tied to two approved therapies in a disease with an estimated 980,000 new cases a year, and the CAR-T approval raises the cost of a false negative."},{"category":"isotope","flag":"green","why":"Gallium-68 works for two of the three published agents; the iodine-124 version would be harder to distribute."},{"category":"competition","flag":"amber","why":"Three groups are already in humans, all in China, so a Western programme would be following rather than leading the science."}],"competition":[{"name":"Chinese academic PET programmes","what":"68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L), each with a published first-in-human pilot of 11 to 17 patients.","stage":"first-in-human","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"name":"Astellas","what":"Zolbetuximab (Vyloy), the approved CLDN18.2 antibody, selected by the VENTANA 43-14A RxDx immunohistochemistry companion diagnostic.","stage":"approved","url":"https://www.prnewswire.com/news-releases/chinas-national-medical-products-administration-nmpa-approves-vyloy-zolbetuximab-for-first-line-treatment-of-advanced-gastric-or-gastroesophageal-junction-adenocarcinoma-302342446.html"},{"name":"CARsgen Therapeutics","what":"Satricabtagene autoleucel, a CLDN18.2 CAR-T reported approved in China in June 2026 for the same biomarker-defined population.","stage":"approved in China","url":"https://chinamedwaypoint.com/resources/cancer-care/cancer-care-in-china/car-t-cell-therapy/ct041-satri-cel-cldn18-2-gastric-cancer-nmpa-approval"},{"name":"Roche Diagnostics","what":"The VENTANA CLDN18 (43-14A) RxDx assay, the incumbent companion diagnostic an imaging agent would be measured against.","stage":"approved companion diagnostic","url":"https://www.cancerbiomed.org/content/22/3/212"}],"differentiation":"The competitor is an approved immunohistochemistry companion diagnostic, not a blood test: liquid biopsy is not used clinically to determine CLDN18.2 status. Imaging does not offer a better biological measurement than histology; it offers coverage of every lesion at once, which is precisely the axis on which the tissue assay has been shown to fail.","metrics":[{"label":"Sensitivity of one representative biopsy for CLDN18.2 against whole-section truth","value":"58.8%","source":"Naujoks et al., Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"False-negative rate across laboratories in a CLDN18.2 immunohistochemistry ring trial","value":"12%","source":"Multi-laboratory ring trial","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"CLDN18.2 positivity at the 75% threshold in 4,507 screened patients","value":"38.4%","source":"Pooled SPOTLIGHT and GLOW screening, Gastric Cancer 2024","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"Tumours discordant between primary and matched nodal metastasis","value":"18%","source":"Naujoks et al., Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"}],"risks":["Regulators may not accept an imaging agent as an alternative route to a therapy whose label names a specific tissue assay, leaving the scan as an adjunct that nobody reimburses.","A scan threshold equivalent to the 75%-of-cells histology cut-off has not been defined, and defining it is a study in itself.","Three Chinese groups are ahead in the clinic, so a later entrant needs a better construct, not just a programme."],"watch":["Whether any of the three published tracers moves to a multicentre trial or reports agreement against the approved companion diagnostic.","Label expansions of CLDN18.2 therapies into earlier lines, which would multiply the number of selection decisions.","Any regulatory statement on non-tissue routes to establishing CLDN18.2 positivity."],"route":"/opportunities/opp-cldn18-2-imaging-gastric/"}
{"id":"opp-trop2-imaging-heterogeneity","kind":"opportunity","name":"TROP2 imaging where no tissue test is required","aka":["TROP2 PET","Trop-2 imaging"],"tldr":"Two approved breast cancer drugs work through a protein called TROP2, and neither requires any test for it before use. Tumours vary a lot in how much they carry, and a quarter of patients lose it over time, so nobody currently knows who is being treated for a target that is no longer there.","summary":"Sacituzumab govitecan and datopotamab deruxtecan are both approved TROP2-directed antibody-drug conjugates, and neither label requires a TROP2 assay. That is not because expression is irrelevant: in the ASCENT biomarker analysis, patients with high TROP2 expression had an objective response rate of 44% against 22% in the low group, with progression-free survival of 6.9 against 2.7 months. It is because the tissue test does not work well enough to gate treatment. A comparison of three immunohistochemistry assays found only fair-to-moderate concordance, there is no validated plasma or ctDNA assay, and a study of circulating tumour cells found no concordance between cell-based and tissue TROP2 status.\n\nHeterogeneity is documented in both space and time: in paired primary and brain-metastasis samples, 21.4% of cases were discordant, and in a longitudinal biopsy series 27.6% of patients showed a marked fall in TROP2 H-score between consecutive time points. Bone metastases showed lower TROP2 than other sites in a post-mortem multi-metastasis study.\n\nThe imaging programmes are Chinese, academic and moving quickly. The nanobody tracer 68Ga-MY6349 completed a 90-patient multi-tumour feasibility study and then a 73-patient breast-specific study published in Theranostics in 2026. Nobody has filed anywhere. Because no companion diagnostic exists to be displaced, an imaging agent here would not be competing with an approved assay but filling a space that both drug labels leave open.","asOf":"2026-09-23","links":[{"label":"68Ga-MY6349 in breast cancer, Theranostics 2026","url":"https://www.thno.org/v16p8117.htm"},{"label":"ASCENT TROP2 biomarker analysis","url":"https://pubmed.ncbi.nlm.nih.gov/34116144/"},{"label":"TROP2 biomarker review: no companion diagnostic, no validated plasma assay","url":"https://biomarker.onclive.com/breast-cancer/triple-negative-tnbc/biomarkers/trop2"},{"label":"Longitudinal fall in TROP2 expression during treatment","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13379550/"},{"label":"FDA approval of datopotamab deruxtecan, January 2025","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast"}],"tags":["target crossover","breast","heterogeneity","nanobody"],"related":["ga-68"],"indications":["breast-triple-negative"],"sections":[],"technologies":["trop2-pet","immuno-pet","pet-ct"],"targets":["trop2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"target-crossover","unmetNeed":"Neither approved TROP2 antibody-drug conjugate requires a test for TROP2, and no validated blood or tissue assay exists, so when a patient stops responding nobody can tell whether the target has been lost or the payload has failed.","useCase":"A breast oncologist would scan before starting a TROP2 antibody-drug conjugate in a patient with several metastatic sites including bone, and again at progression, to distinguish loss of target from resistance to the payload. In practice the first real use is inside trials, deciding whether target level predicts benefit well enough to justify a clinical test at all.","hypothesis":"Whole-body TROP2 quantification will predict benefit from TROP2-directed antibody-drug conjugates better than tissue immunohistochemistry, because the observed 21% primary-to-metastasis discordance and the 28% of patients with a marked longitudinal fall in expression are exactly the errors a single biopsy cannot avoid and imaging can.","rationale":"Unlike HER3, there is already a published expression-response gradient for a TROP2 drug: 44% against 22% objective response by expression level in ASCENT. The reason that gradient has not become a test is assay failure rather than absent biology, and the failures are specifically of sampling and standardisation, which is the class of problem imaging addresses. Nanobody constructs give same-day imaging, and one has already been through 90 patients across tumour types and then a 73-patient disease-specific study.","test":"A study embedded in a TROP2 antibody-drug conjugate trial: image before treatment, relate uptake to objective response and progression-free survival, and re-image at progression in a subset to measure change in target. The primary question is whether an imaging threshold separates responders better than the published immunohistochemistry cut-offs did in ASCENT.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"68Ga-MY6349, a TROP2 nanobody tracer from Shanghai Novamab studied at Xiamen and Fudan, with a completed 90-patient multi-tumour study and a 73-patient breast-cancer study published in Theranostics in 2026.","dueDiligence":[{"domain":"target-biology","state":"moderate","why":"TROP2 is widely expressed in breast cancer but with marked intratumoral heterogeneity and discordance between primary and metastatic sites; membranous rather than cytoplasmic localisation appears to matter more than total intensity.","source":"TROP2 biomarker review","url":"https://biomarker.onclive.com/breast-cancer/triple-negative-tnbc/biomarkers/trop2","weighted":true},{"domain":"clinical-evidence","state":"moderate","why":"One nanobody tracer has a completed 90-patient feasibility study and a published 73-patient breast-specific study; all of it academic, single-country and not registrational.","source":"Theranostics 2026","url":"https://www.thno.org/v16p8117.htm"},{"domain":"diagnostic-performance","state":"thin","why":"No study relates tracer uptake to antibody-drug conjugate response. The comparator's performance is the strongest published signal: ASCENT reported 44% against 22% objective response by TROP2 expression level.","source":"ASCENT biomarker analysis","url":"https://pubmed.ncbi.nlm.nih.gov/34116144/","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No adverse events reported in the published nanobody cohorts, but no formal dosimetry figure has been published that is worth quoting."},{"domain":"regulatory-path","state":"thin","why":"There is no TROP2 companion diagnostic to anchor a claim, and neither drug label requires testing, so an imaging agent would have to define its own indication, most plausibly as an adjunct rather than a selection gate.","source":"TROP2 biomarker review","url":"https://biomarker.onclive.com/breast-cancer/triple-negative-tnbc/biomarkers/trop2"}],"flags":[{"category":"technical","flag":"green","why":"A nanobody construct labelled with gallium-68 already images in humans with same-day kinetics, which is the format this kind of agent needs."},{"category":"unmet-need","flag":"amber","why":"Real heterogeneity and a published expression-response gradient, but both drugs are prescribed today without any test, so the clinical pull is weaker than the biology suggests."},{"category":"ip","flag":"amber","why":"The leading construct is owned by a Chinese biotech and studied with academic partners; no Western clinical programme is disclosed."},{"category":"commercial","flag":"amber","why":"Two approved drugs and expanding indications make the addressable population large, but a test that neither label requires has to earn reimbursement on its own evidence."},{"category":"isotope","flag":"green","why":"Gallium-68 on a nanobody; nothing scarce."},{"category":"competition","flag":"amber","why":"The Chinese programme is several years and roughly 160 patients ahead of anyone else."}],"competition":[{"name":"Shanghai Novamab with Xiamen and Fudan centres","what":"68Ga-MY6349 nanobody PET; completed 90-patient multi-tumour study and a published 73-patient breast-cancer study.","stage":"early clinical","url":"https://www.thno.org/v16p8117.htm"},{"name":"Gilead","what":"Sacituzumab govitecan, approved since 2020 across triple-negative and HR-positive breast cancer; no TROP2 test required.","stage":"approved","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer"},{"name":"Daiichi Sankyo and AstraZeneca","what":"Datopotamab deruxtecan, approved January 2025 for HR-positive disease and later in triple-negative disease; no TROP2 test required.","stage":"approved","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast"}],"differentiation":"There is no approved companion diagnostic, no validated plasma or ctDNA assay, and circulating-tumour-cell TROP2 does not agree with tissue. A quantitative digital-pathology score has separated responders in lung cancer but remains investigational and has no role in breast cancer today. An imaging agent would therefore be competing against nothing, which is both the opportunity and the reason reimbursement would be hard.","metrics":[{"label":"Objective response rate, high against low TROP2 expression in ASCENT","value":"44% against 22%","source":"ASCENT biomarker analysis","url":"https://pubmed.ncbi.nlm.nih.gov/34116144/"},{"label":"Paired primary and brain-metastasis samples discordant for TROP2","value":"21.4% of 14","source":"Paired-sample immunohistochemistry study","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12531291/"},{"label":"Patients with a marked longitudinal fall in TROP2 H-score","value":"27.6%","source":"Longitudinal biopsy series","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13379550/"},{"label":"Concordance between three TROP2 immunohistochemistry assays","value":"fair to moderate (AC2 0.35)","source":"Assay comparison study","url":"https://ngdc.cncb.ac.cn/openlb/publication/OLB-PM-40914741"}],"risks":["Neither drug label requires a test, so oncologists have no workflow reason to order a scan and payers have no reason to fund it.","If the expression-response gradient does not reproduce in the datopotamab deruxtecan datasets, the predictive premise weakens.","The leading construct is already in a second disease-specific study, so a new entrant starts well behind."],"watch":["Any published relationship between TROP2 tracer uptake and antibody-drug conjugate response, which is the missing link in the whole case.","Whether a quantitative digital-pathology score reaches the breast cancer label, which would make a tissue test the standard and box in the scan.","Registration of a TROP2 imaging trial outside China, which would be the first sign of industry interest."],"route":"/opportunities/opp-trop2-imaging-heterogeneity/"}
{"id":"opp-caix-indeterminate-renal-mass","kind":"opportunity","name":"CAIX imaging of the indeterminate renal mass","aka":["CA9 imaging","girentuximab PET"],"tldr":"Scans find small kidney lumps all the time and cannot tell which are cancer. Up to one in five that are surgically removed turn out to be harmless. A scan that recognises the commonest kidney cancer would spare those operations, and it needs no drug to be useful.","summary":"This is the cleanest standalone diagnostic case in the field: the scan answers a question on its own, with no therapy dependency. Between 12.8% and 40% of surgically resected small renal masses are benign depending on size, and no imaging technique reliably defines histological subtype before surgery.\n\nThe lead agent has the evidence. 89Zr-girentuximab (TLX250-CDx, Zircaix) reported phase 3 ZIRCON results in Lancet Oncology in October 2024: 300 patients dosed, 284 evaluable, sensitivity 85.5% and specificity 87.0% for clear cell renal cell carcinoma, with no safety signals. The BLA was accepted with priority review and a PDUFA date of 27 August 2025, but the FDA issued a complete response letter on chemistry, manufacturing and controls rather than efficacy or safety; the sponsor has since reported agreement on remediation after Type A meetings. It remains unapproved anywhere.\n\nBehind it sit peptide and small-molecule CAIX ligands with same-day kinetics: 68Ga-DPI-4452 has FDA Fast Track designation and first-in-human data, and a technetium-99m CAIX peptide and a gallium-68 CAIX agent have small first-in-human cohorts. Chinese academic work includes a 47-patient 68Ga-NY104 cohort. The opportunity split is therefore sharp: the antibody owns the evidence and the regulatory queue, while the unmet need for a same-day, widely distributable agent is unmet by definition because no peptide has a phase 3.","asOf":"2026-09-23","links":[{"label":"ZIRCON phase 3, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"NCT03849118: ZIRCON","url":"https://clinicaltrials.gov/study/NCT03849118"},{"label":"Girentuximab dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8426244/"},{"label":"Benign proportion of resected small renal masses","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2797464/"}],"tags":["standalone diagnostic","kidney","biopsy avoidance"],"related":["zr-89","ga-68","tc-99m"],"indications":["rcc"],"sections":[],"technologies":["caix-pet","immuno-pet","pet-ct"],"targets":["caix"],"drugs":["girentuximab-zr89","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"standalone-diagnostic","unmetNeed":"When CT or MRI finds an indeterminate renal mass, nothing tells the clinician whether it is clear cell renal cell carcinoma before committing the patient to surgery, biopsy or surveillance, and up to a fifth of resected small masses prove benign.","useCase":"A urologist would order it for the indeterminate small renal mass, to separate clear cell carcinoma from benign or non-clear-cell lesions before deciding between surgery, ablation and surveillance; and in metastatic disease to characterise lesions of uncertain origin. It requires no drug approval to be worth doing, which is what makes it a standalone opportunity.","hypothesis":"A same-day CAIX ligand will reach the diagnostic accuracy that the antibody achieved in ZIRCON while allowing imaging within hours of injection, making the test deliverable in a routine urology pathway rather than requiring a return visit days later.","rationale":"CAIX is expressed in over 90% of clear cell renal cell carcinomas because VHL loss leaves the HIF pathway constitutively active, and essentially absent in normal kidney, which is why the antibody reached 85.5% sensitivity and 87.0% specificity in a 284-patient phase 3. The antibody's limitation is kinetic, not biological: a full antibody labelled with zirconium-89 requires imaging days after injection. Peptide and small-molecule ligands have already shown human uptake, and the precedent from other target classes is that the small-molecule generation displaces the antibody once accuracy is matched.","test":"A prospective multicentre study of a same-day CAIX ligand in patients with an indeterminate renal mass scheduled for resection or biopsy, with histopathology as the truth standard, powered for sensitivity and specificity against the ZIRCON benchmark of 85.5% and 87.0%, and reporting the proportion of planned operations avoided.","maturity":"being-tested-at-scale","verdict":"standalone-only","mostAdvanced":"89Zr-girentuximab (TLX250-CDx, Telix), phase 3 ZIRCON published in Lancet Oncology 2024, BLA accepted with priority review but issued a complete response letter on manufacturing in August 2025 and unapproved anywhere.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"CAIX is expressed in over 90% of clear cell renal cell carcinoma through constitutive HIF-1 activity after VHL loss, and is essentially absent from normal renal parenchyma.","source":"Nuclide CAIX target record and the ZIRCON literature","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"domain":"clinical-evidence","state":"strong","why":"A completed phase 3 of 300 dosed and 284 evaluable patients published in Lancet Oncology, the only phase 3 diagnostic dataset for any CAIX agent.","source":"ZIRCON, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/","weighted":true},{"domain":"diagnostic-performance","state":"strong","why":"Sensitivity 85.5% (95% CI 81.5 to 89.6) and specificity 87.0% (81.0 to 93.1) for clear cell renal cell carcinoma in ZIRCON.","source":"ZIRCON, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/","weighted":true},{"domain":"safety-dosimetry","state":"strong","why":"No safety signals in the phase 3; girentuximab whole-body effective dose is reported at 0.57 plus or minus 0.08 mSv/MBq.","source":"ZIRCON and published dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8426244/"},{"domain":"regulatory-path","state":"moderate","why":"The pathway is proven to the point of a priority-review BLA, then blocked: the FDA issued a complete response letter on chemistry, manufacturing and controls, not on efficacy or safety, and the product is approved nowhere.","source":"Sponsor and partner disclosures","url":"https://heidelberg-pharma.com/en/research-development/other-projects"}],"flags":[{"category":"technical","flag":"amber","why":"The proven agent is a zirconium-89 antibody imaged days after injection; the same-day peptides have small cohorts and no accuracy dataset."},{"category":"unmet-need","flag":"green","why":"Up to 15 to 20% of resected small renal masses are benign and no imaging test defines subtype, so the scan prevents operations rather than selecting drugs."},{"category":"ip","flag":"red","why":"The antibody and its phase 3 dataset are owned, and several peptide and small-molecule CAIX ligands are already claimed by companies with first-in-human data; entering now means designing around a crowded space."},{"category":"commercial","flag":"green","why":"Standalone by construction: reimbursement rests on avoided surgery, not on another company's drug approval, which is the strongest commercial position a diagnostic can have."},{"category":"isotope","flag":"amber","why":"Zirconium-89 is cyclotron-made with limited distribution; a gallium-68 or fluorine-18 ligand would remove that constraint."},{"category":"competition","flag":"red","why":"A phase 3 agent sits in the regulatory queue and at least three peptide or small-molecule programmes have human data, so the field is contested at every stage."}],"competition":[{"name":"Telix Pharmaceuticals","what":"89Zr-girentuximab (TLX250-CDx, Zircaix): phase 3 ZIRCON published, BLA accepted with priority review, complete response letter on manufacturing August 2025.","stage":"filed, not approved","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"name":"ITM Isotope Technologies Munich","what":"68Ga-DPI-4452, a small peptide CAIX ligand with FDA Fast Track designation in November 2025 and a three-patient first-in-human report in the Journal of Nuclear Medicine.","stage":"early clinical","url":"https://jnm.snmjournals.org/"},{"name":"Philochem","what":"99mTc-PHC-102 with a five-patient cohort, and 68Ga-OncoCAIX with a clinical trial application submitted.","stage":"first-in-human","url":"https://www.philochem.ch/"},{"name":"Chinese academic programmes","what":"68Ga-NY104, a CAIX agent with a 47-patient cohort.","stage":"early clinical"}],"differentiation":"The alternative today is percutaneous renal mass biopsy, which is invasive, sometimes non-diagnostic and not universally offered, or surveillance, which defers the question. There is no blood test for renal cell carcinoma subtype. This is the rare imaging case where the competitor is a procedure rather than another test.","metrics":[{"label":"Sensitivity of 89Zr-girentuximab for clear cell renal cell carcinoma in ZIRCON","value":"85.5%","source":"Lancet Oncology 2024, 284 evaluable patients","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Specificity in the same trial","value":"87.0%","source":"ZIRCON, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Surgically resected small renal masses that prove benign","value":"12.8% to 40% by size","source":"AUA guideline and published series","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2797464/"}],"risks":["The category may be closed before a second entrant arrives: if the manufacturing remediation succeeds, an approved antibody becomes the standard of care and the bar for a peptide rises to non-inferiority against an approved product.","A same-day ligand has to match an 85% and 87% benchmark set in a 284-patient phase 3, which is an expensive trial to run second.","Reimbursement for avoided surgery requires a health-economic case, not just accuracy."],"watch":["Whether the manufacturing complete response letter is resolved and TLX250-CDx is approved, which would reset the benchmark from unmet need to non-inferiority.","Accuracy data from any same-day CAIX peptide, particularly 68Ga-DPI-4452 after its Fast Track designation.","Any European filing, since no EMA submission for the antibody has been found."],"route":"/opportunities/opp-caix-indeterminate-renal-mass/"}
{"id":"opp-grpr-psma-negative-prostate","kind":"opportunity","name":"GRPR imaging when the PSMA scan is negative","aka":["GRPR PET","bombesin receptor imaging"],"tldr":"Prostate cancer imaging and treatment both rely on one protein, PSMA. In a minority of men the tumour does not carry it, and for those men a negative scan is a dead end. A second receptor, GRPR, is the best-studied alternative, and the honest reading of the head-to-head studies is that it finds fewer lesions overall but different ones.","summary":"PSMA has become the single axis of prostate cancer molecular imaging and radioligand therapy, which means the patient whose tumour does not express it has nowhere to go. The published estimates of how large that group is vary by how it is measured: around 5 to 10% of primary tumours are PSMA-negative on immunohistochemistry and around 10% are negative on PSMA PET despite a high PSA, while a commentary puts the figure at 15 to 25% of metastatic castration-resistant patients whose tumours do not significantly express PSMA.\n\nGRPR is the most clinically mature alternative. 68Ga-RM2 has a completed phase 2/3 imaging trial published in Lancet Oncology in 2024: of 209 men screened, 100 were analysed, and RM2 PET-MRI was positive in 69% against 40% for MRI alone, with no grade 1 or worse events. But the head-to-head studies are not a story of superiority. At Stanford, in 50 patients imaged with both, PSMA-directed tracers found 36 extra lesions in 13 patients while RM2 found 7 extra in 4 patients. In a Chilean mCRPC cohort of 17 patients referred for radioligand therapy, PSMA detected 23% more lesions, though in 4 of 17 the two distributions were comparable. A Bordeaux study found the two discordant in 18.8% of lesions, with RM2 better at low-ISUP tumours and PSMA better at clinically significant ones.\n\nThat is the shape of the real opportunity: not a replacement for PSMA PET but a second-look agent for the specific patient in whom PSMA imaging has failed, and a selection test for GRPR-directed therapy. 177Lu-NeoB from Advanced Accelerator Applications has completed phase 1 in NeoRay with a maximum tolerated dose of 9.25 GBq in 17 patients, and 177Lu-RM2 has first-in-human dosimetry in 4 mCRPC patients selected precisely because they had insufficient PSMA expression.","asOf":"2026-09-23","links":[{"label":"68Ga-RM2 phase 2/3, Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38423030/"},{"label":"68Ga-RM2 against PSMA tracers head to head, J Nucl Med 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8612333/"},{"label":"177Lu-RM2 first-in-human dosimetry in PSMA-insufficient patients","url":"https://pubmed.ncbi.nlm.nih.gov/31482426/"},{"label":"NCT03872778: NeoRay, 177Lu-NeoB","url":"https://clinicaltrials.gov/study/NCT03872778"},{"label":"GRPR distribution in cancer, J Nucl Med 2020","url":"https://jnm.snmjournals.org/content/61/6/792"}],"tags":["unmet need first","prostate","PSMA-negative","second-look imaging"],"related":["ga-68","lu-177"],"indications":["prostate-mcrpc","prostate-bcr"],"sections":[],"technologies":["psma-pet","pet-ct","radioligand-therapy","peptide-drug-conjugate"],"targets":["grpr","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"When a man with clinically obvious prostate cancer has a negative or low-uptake PSMA PET, nothing tells his clinician whether the disease is genuinely small-volume, PSMA-negative but targetable through another receptor, or dedifferentiated and beyond either.","useCase":"A prostate multidisciplinary team would order a GRPR scan as a second look after a negative or discordant PSMA PET in a man whose PSA says the disease is there, and as the selection test before GRPR-directed radioligand therapy in a patient who has exhausted PSMA-directed options.","hypothesis":"In the subgroup defined by a negative or low-uptake PSMA PET, GRPR imaging will identify disease that PSMA imaging missed at a rate high enough to change management, even though in unselected patients it detects fewer lesions than PSMA imaging does.","rationale":"GRPR overexpression has been reported in 63 to 100% of prostate cancers, and the receptor is inversely related to PSMA in part of the disease, which is why the first patients treated with 177Lu-RM2 were chosen for insufficient PSMA expression. The imaging agent has the largest dataset of any non-PSMA prostate tracer, including a completed phase 2/3 trial, and the therapeutic pair exists with a defined phase 2 dose. The lesion-level studies that look unfavourable to GRPR were all run in unselected patients, which is the wrong population for this hypothesis.","test":"A prospective study enrolling only men with a negative or equivocal PSMA PET and biochemical or clinical evidence of disease, imaging them with a GRPR tracer, with histology or subsequent conventional imaging as the truth standard, and reporting the proportion in whom a management-changing lesion was found. Enrolment on the PSMA-negative criterion is the whole design; the existing unselected head-to-heads have already answered the other question.","maturity":"being-tested-at-scale","verdict":"standalone-and-companion","mostAdvanced":"68Ga-RM2 for imaging, with a completed phase 2/3 trial (NCT02624518, 100 patients analysed) published in Lancet Oncology 2024; on the therapy side 177Lu-NeoB from Advanced Accelerator Applications, phase 1 complete in NeoRay (NCT03872778) with a maximum tolerated dose of 9.25 GBq.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"GRPR overexpression has been reported in 63 to 100% of prostate cancers, and preclinical work found high 177Lu-NeoB binding in PSMA-negative castration-resistant samples, which is the inverse relationship the whole case depends on.","source":"Frontiers in Oncology 2023 review","url":"https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1199432/full","weighted":true},{"domain":"clinical-evidence","state":"strong","why":"A completed phase 2/3 imaging trial of 100 analysed patients published in Lancet Oncology, plus three published head-to-head comparisons against PSMA tracers and a phase 1 therapy dataset.","source":"Duan et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38423030/","weighted":true},{"domain":"diagnostic-performance","state":"moderate","why":"68Ga-RM2 PET-MRI was positive in 69% of patients against 40% for MRI alone, but against PSMA tracers it detected fewer lesions: 7 extra in 4 patients versus 36 extra in 13 patients across 50 men imaged with both.","source":"Baratto et al., J Nucl Med 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8612333/","weighted":true},{"domain":"safety-dosimetry","state":"strong","why":"No grade 1 or worse events were reported in the 100-patient imaging trial; on the therapy side mean absorbed dose was 1.08 plus or minus 0.44 Gy/GBq in the pancreas and 6.20 plus or minus 3.00 Gy/GBq in tumour lesions, with no side effects observed in four treated patients.","source":"Kurth et al., EJNMMI 2020","url":"https://pubmed.ncbi.nlm.nih.gov/31482426/"},{"domain":"regulatory-path","state":"moderate","why":"Receptor-targeted PET has an accepted non-inferiority route: NETSPOT was approved in June 2016 on non-inferiority of performance characteristics against OctreoScan, without an advisory committee. No GRPR imaging agent has been filed anywhere.","source":"FDA approval package, NETSPOT","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208547Orig1s000Approv.pdf"}],"flags":[{"category":"technical","flag":"green","why":"Gallium-68 labelled antagonist peptides with same-day imaging and a published clean safety record; the chemistry is not the problem here."},{"category":"unmet-need","flag":"green","why":"A PSMA-negative scan currently ends the pathway, and the population is somewhere between 10% on PET and a reported 15 to 25% of metastatic castration-resistant disease."},{"category":"ip","flag":"amber","why":"RM2 originated at Bayer and is developed academically at Stanford; NeoB belongs to Advanced Accelerator Applications; a new entrant would need its own antagonist scaffold."},{"category":"commercial","flag":"amber","why":"Standalone as a second-look scan and a companion for GRPR therapy, but the addressable group is defined by another test's failure, which makes volume a function of PSMA PET throughput."},{"category":"isotope","flag":"green","why":"Gallium-68 for imaging and lutetium-177 for therapy; both established supply chains."},{"category":"competition","flag":"amber","why":"Novartis through Advanced Accelerator Applications holds the most advanced therapy and its companion tracer, so the therapeutic pairing is largely taken."}],"competition":[{"name":"Stanford University","what":"68Ga-RM2, completed phase 2/3 imaging trial in biochemical recurrence, 100 patients analysed, published in Lancet Oncology 2024.","stage":"phase 2/3 complete","url":"https://clinicaltrials.gov/study/NCT02624518"},{"name":"Advanced Accelerator Applications (Novartis)","what":"177Lu-NeoB with its 68Ga-NeoB companion; NeoRay phase 1 complete, maximum tolerated dose 9.25 GBq, 35-patient target enrolment across 18 sites in 6 countries.","stage":"phase 1/2a","url":"https://clinicaltrials.gov/study/NCT03872778"},{"name":"Rostock University Medical Center","what":"177Lu-RM2 and 177Lu-AMTG first-in-human dosimetry, four patients treated after screening 35 with 68Ga-RM2 PET/CT.","stage":"first-in-human","url":"https://pubmed.ncbi.nlm.nih.gov/31482426/"}],"differentiation":"The percentage of PSMA-negative tumour area on immunohistochemistry is reported as an independent prognostic factor but is not a clinical decision tool, and no ctDNA or blood test identifies a GRPR-positive compartment. Imaging is the only way to establish target expression at every lesion at once, which is exactly what a patient with a discordant PSMA scan needs.","metrics":[{"label":"68Ga-RM2 PET-MRI positive rate against MRI alone in biochemical recurrence","value":"69% against 40% of 100 patients","source":"Duan et al., Lancet Oncology 2024","url":"https://pubmed.ncbi.nlm.nih.gov/38423030/"},{"label":"Extra lesions found by each tracer in 50 patients imaged with both","value":"PSMA 36 lesions in 13 patients; RM2 7 lesions in 4 patients","source":"Baratto et al., J Nucl Med 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8612333/"},{"label":"Primary prostate cancers negative on PSMA PET despite high PSA","value":"around 10%","source":"Published review","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7255040/"},{"label":"Maximum tolerated dose of 177Lu-NeoB in phase 1","value":"9.25 GBq","source":"Phase 1 NeoRay report","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12866383/"}],"risks":["In unselected patients GRPR imaging detects fewer lesions than PSMA imaging, so the agent only makes sense in a narrow, test-defined subgroup and must be trialled that way.","There is no agreed definition of a PSMA-negative scan, so the enrolment criterion for the pivotal study has to be constructed before the study can run.","The most advanced therapeutic pairing sits inside Novartis, which limits partnering options for an independent imaging agent."],"watch":["Any trial that enrols on PSMA-negativity rather than on known measurable disease, which would be the first real test of this hypothesis.","Phase 2a efficacy from NeoRay in the prostate cohort, which determines whether a companion diagnostic has a therapy to serve.","Whether the 15 to 25% mCRPC figure is ever established by a primary dataset rather than commentary; the size of the opportunity turns on it."],"route":"/opportunities/opp-grpr-psma-negative-prostate/"}
{"id":"opp-cxcr4-primary-aldosteronism","kind":"opportunity","name":"CXCR4 imaging instead of adrenal vein sampling","aka":["PentixaFor PET","CXCR4 PET in primary aldosteronism"],"tldr":"A common and curable cause of high blood pressure is almost never cured, because finding out which adrenal gland is at fault needs an invasive procedure few hospitals do well. A PET scan can answer the same question, and one is now heading into a registrational trial.","summary":"Primary aldosteronism accounts for 5 to 14% of all hypertension and 20 to 25% of treatment-resistant hypertension, and it can be cured by removing one adrenal gland if the excess comes from one side. Establishing which side requires adrenal vein sampling, an invasive procedure that the MATCH investigators describe as requiring a day off work, causing severe pain and hospitalisation in 1 to 3% of patients, available with a success rate above 50% in few hospitals. The consequence they report is stark: fewer than 1% of patients with primary aldosteronism are identified and fully investigated.\n\nThis is not a radiopharmaceutical looking for a use. It is the clearest standalone diagnostic case outside oncology, and it is already being built. 68Ga-PentixaFor from Pentixapharm holds EMA PRIME status granted in October 2024 and FDA Fast Track designation granted in July 2026, with an IND cleared and a phase 3 trial, PANDA, planned at approximately 270 patients in the United States. The academic evidence behind it is substantial: in a 100-patient prospective study, PET/CT agreed with adrenal vein sampling in 90% of patients against 54% for conventional CT, and a meta-analysis of seven studies covering 603 patients has been reported at pooled sensitivity 80% and specificity 91%.\n\nThe agent is also validated against pathology rather than just against another test: consistency between PET uptake and CXCR4 staining was 92.9%, and all 43 CYP11B2-positive functional nodules in one series were CXCR4-positive. What makes this record worth carrying is not that anything is missing, but that it is the field's best worked example of what an unmet-need-first opportunity looks like when it succeeds.","asOf":"2026-09-23","links":[{"label":"MATCH: molecular imaging against adrenal vein sampling, Nature Medicine 2023","url":"https://www.nature.com/articles/s41591-022-02114-5"},{"label":"68Ga-pentixafor against adrenal vein sampling in 100 patients, JAMA Network Open 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9936343/"},{"label":"FDA Fast Track designation for 68Ga-PentixaFor in primary aldosteronism","url":"https://www.eqs-news.com/news/corporate/pentixapharm-receives-fda-fast-track-designation-for-phase-3-diagnostic-candidate-e281b6e281b8gaga-pentixafor-in-primary-aldosteronism/239d14bc-6e9e-4077-9909-43e52edf7a09_en"},{"label":"EMA PRIME status for 68Ga-PentixaFor","url":"https://www.pentixapharm.com/news/ema-grants-prime-status-to-pentixapharms-lead-candidate-pentixafor"},{"label":"68Ga-pentixafor dosimetry, J Nucl Med 2015","url":"https://jnm.snmjournals.org/content/56/3/410"},{"label":"Endocrine Society primary aldosteronism guideline 2025","url":"https://www.endocrine.org/clinical-practice-guidelines/primary-aldosteronism-2"}],"tags":["unmet need first","standalone diagnostic","non-oncology","hypertension"],"related":["ga-68"],"indications":["primary-aldosteronism"],"sections":[],"technologies":["pet-ct","pet"],"targets":["cxcr4"],"drugs":["ga-68-pentixafor"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"A curable cause of hypertension goes untreated because the test that decides who can be cured is invasive, painful, available in few centres and therefore almost never done: fewer than 1% of patients with primary aldosteronism are fully investigated.","useCase":"An endocrinologist or hypertension specialist with a confirmed diagnosis of primary aldosteronism would use the scan to decide between adrenalectomy and lifelong medical therapy, replacing adrenal vein sampling. The value is measured in operations correctly offered, not in lesions detected.","hypothesis":"CXCR4-targeted PET will lateralise primary aldosteronism accurately enough to replace adrenal vein sampling, and by removing the invasive step will raise the proportion of patients investigated and cured well above the current figure of fewer than 1%.","rationale":"CXCR4 is expressed on aldosterone-producing tissue and tracks the pathology marker: all CYP11B2-positive functional nodules in one series were CXCR4-positive, with 92.9% consistency between PET uptake and staining. Against the invasive reference standard, PET/CT concordance was 90% against CT's 54% in 100 patients, and surgical outcomes support it, with complete biochemical and clinical success of 91.67% and 100% in 36 patients operated on the basis of PET lateralisation. The molecular-imaging approach has already been shown non-inferior to adrenal vein sampling with a different tracer in the MATCH trial, so the regulatory logic is established.","test":"The registrational design is already defined: a multicentre trial benchmarking PET lateralisation against a performance standard derived from guideline-based diagnosis, with post-adrenalectomy biochemical and clinical cure as the outcome that matters. The open question this record tracks is whether phase 3 reproduces the 90% concordance seen in single-centre studies.","maturity":"being-tested-at-scale","verdict":"standalone-only","mostAdvanced":"68Ga-PentixaFor (Pentixapharm Holding AG): EMA PRIME status October 2024, FDA Fast Track July 2026, IND cleared, phase 3 PANDA planned at approximately 270 patients in the United States with US launch targeted for 2030.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"All 43 CYP11B2-positive functional nodules in one series were CXCR4-positive, and consistency between PET uptake and CXCR4 staining was 92.9%, tying the imaging signal directly to the enzyme that makes aldosterone.","source":"Functional nodules study, PMID 36070092","url":"https://pubmed.ncbi.nlm.nih.gov/36070092/","weighted":true},{"domain":"clinical-evidence","state":"strong","why":"Multiple completed prospective studies including 100 patients against adrenal vein sampling, 120 patients with pathology correlation, and a randomised 320-patient trial recruiting in China; an approximately 270-patient US phase 3 is planned.","source":"Hu et al., JAMA Network Open 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9936343/","weighted":true},{"domain":"diagnostic-performance","state":"strong","why":"PET/CT agreed with adrenal vein sampling in 90 of 100 patients against 54 of 100 for conventional CT; a reported meta-analysis of seven studies and 603 patients gives pooled sensitivity 80% and specificity 91% with an AUC of 0.91.","source":"Hu et al., JAMA Network Open 2023; meta-analysis via a 2026 review","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9936343/","weighted":true},{"domain":"safety-dosimetry","state":"strong","why":"Effective dose from 150 MBq of 68Ga-pentixafor is 2.3 mSv, with the highest organ dose in the bladder wall at 12.2 mGy; a 2025 dosimetry paper reports 1.65 plus or minus 0.06 mSv for the same activity, both far below the 7 mSv of a standard FDG scan.","source":"Herrmann et al., J Nucl Med 2015","url":"https://jnm.snmjournals.org/content/56/3/410","weighted":true},{"domain":"regulatory-path","state":"strong","why":"EMA PRIME and FDA Fast Track are both granted for this exact indication, the IND has cleared, and written FDA minutes reportedly identified no major concerns with the phase 3 design.","source":"Pentixapharm and EQS releases","url":"https://www.eqs-news.com/news/corporate/pentixapharm-receives-fda-fast-track-designation-for-phase-3-diagnostic-candidate-e281b6e281b8gaga-pentixafor-in-primary-aldosteronism/239d14bc-6e9e-4077-9909-43e52edf7a09_en","weighted":true}],"flags":[{"category":"technical","flag":"green","why":"Gallium-68 small-molecule ligand, same-day imaging, effective dose around 2 mSv, and pathology-validated uptake."},{"category":"unmet-need","flag":"green","why":"A curable disease in 5 to 14% of all hypertension where fewer than 1% of patients are fully investigated because the deciding test is invasive."},{"category":"ip","flag":"red","why":"The ligand was patented at the University of Würzburg and exclusively licensed to Pentixapharm in 2019, so the lead chemical series is not available."},{"category":"commercial","flag":"green","why":"Purely standalone: the scan replaces a procedure and depends on no drug approval, which is the strongest commercial structure a diagnostic can have."},{"category":"isotope","flag":"green","why":"Gallium-68 from a generator; no supply constraint."},{"category":"competition","flag":"red","why":"One sponsor holds PRIME, Fast Track and a cleared IND in this indication, and the metomidate tracers are an established academic alternative; a new entrant would be third at best."}],"competition":[{"name":"Pentixapharm Holding AG","what":"68Ga-PentixaFor: EMA PRIME, FDA Fast Track, IND cleared, phase 3 PANDA planned at approximately 270 patients, US launch targeted 2030.","stage":"phase 3 planned","url":"https://www.pentixapharm.com/news/ema-grants-prime-status-to-pentixapharms-lead-candidate-pentixafor"},{"name":"National Cancer Institute and NIDDK","what":"Investigator-initiated phase 2 of 68Ga-PentixaFor in hyperaldosteronism and hypercortisolism, 80 patients estimated.","stage":"phase 2 recruiting","url":"https://clinicaltrials.gov/study/NCT06246357"},{"name":"First Affiliated Hospital of Chongqing Medical University","what":"Multicentre randomised trial of PET/CT-guided against adrenal-vein-sampling-guided treatment, 320 participants estimated.","stage":"recruiting","url":"https://classic.clinicaltrials.gov/ct2/show/NCT06238232"},{"name":"UK academic consortium (Barts, Cambridge, Guy's)","what":"[11C]metomidate and [18F]CETO, the non-CXCR4 precedent: molecular imaging reported non-inferior to adrenal vein sampling in MATCH, 146 patients.","stage":"published","url":"https://www.nature.com/articles/s41591-022-02114-5"}],"differentiation":"The aldosterone-to-renin ratio screens for the disease but does not say which side; CYP11B2 immunohistochemistry confirms the answer only after the gland has been removed; and no blood or ctDNA test lateralises the disease before surgery. The comparator here is an invasive procedure, not another scan, which is why the health-economic case is unusually direct.","metrics":[{"label":"Concordance of 68Ga-pentixafor PET/CT with adrenal vein sampling against CT","value":"90 of 100 patients against 54 of 100","source":"Hu et al., JAMA Network Open 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9936343/"},{"label":"Primary aldosteronism as a share of all hypertension","value":"5 to 14%","source":"Wu et al., Nature Medicine 2023","url":"https://www.nature.com/articles/s41591-022-02114-5"},{"label":"Patients with primary aldosteronism identified and fully investigated","value":"fewer than 1%","source":"Wu et al., Nature Medicine 2023","url":"https://www.nature.com/articles/s41591-022-02114-5"},{"label":"Post-adrenalectomy complete biochemical and clinical success after PET-guided surgery in bilateral lesions","value":"91.67% and 100% of 36 patients","source":"EJNMMI Research 2025","url":"https://link.springer.com/article/10.1186/s13550-025-01309-4"},{"label":"Effective dose from 150 MBq of 68Ga-pentixafor","value":"2.3 mSv","source":"Herrmann et al., J Nucl Med 2015","url":"https://jnm.snmjournals.org/content/56/3/410"}],"risks":["Single-centre concordance of 90% may not survive a multicentre phase 3 with central reading.","The indication sits with endocrinologists and hypertension specialists who do not routinely order PET, so adoption is a referral-pathway problem as much as an accuracy one.","The chemical series is exclusively licensed, so this is a record to learn the method from rather than an opening to enter."],"watch":["Registration of PANDA on ClinicalTrials.gov and its first patient enrolled, expected in the second half of 2026 per the sponsor.","The Chongqing randomised trial, which is the only design that tests whether PET-guided treatment produces the same cures as sampling-guided treatment.","Whether guideline bodies begin to name molecular imaging as an alternative to adrenal vein sampling."],"route":"/opportunities/opp-cxcr4-primary-aldosteronism/"}
{"id":"opp-alpha-synuclein-pet-parkinsons","kind":"opportunity","name":"Alpha-synuclein PET: works for MSA, not for Parkinson's","aka":["a-synuclein PET","ACI-12589"],"tldr":"Parkinson's disease is defined by a protein clumping in the brain, and no scan can see it. The first tracer to reach patients does light up a rarer, related disease but not Parkinson's itself, while a spinal-fluid test already identifies Parkinson's with high accuracy.","summary":"Amyloid and tau both have approved PET agents. Alpha-synuclein, the protein that defines Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, has none: no small molecule targeting misfolded alpha-synuclein has been approved by the FDA as a PET radiopharmaceutical. The clinical consequence is that early Parkinson's cannot be separated from multiple system atrophy or progressive supranuclear palsy when the picture is ambiguous, and no anti-alpha-synuclein drug programme can show target engagement in a living brain.\n\nThe most advanced agent is [18F]ACI-12589 from AC Immune, with a 42-participant published dataset in Nature Communications in 2023: 8 healthy controls, 8 Parkinson's, 2 dementia with Lewy bodies, 13 multiple system atrophy, 3 progressive supranuclear palsy, 5 Alzheimer's and 3 hereditary ataxias. The result is a genuine partial success and a genuine partial failure. Binding statistically separated multiple system atrophy patients from controls and from other neurodegenerative disorders, with clear signal in cerebellar white matter and middle cerebellar peduncles, but limited binding in Parkinson's disease; a conference report put it more bluntly, that PET signals were undetectable in other synucleinopathies despite the tracer binding post-mortem tissue from those same disorders.\n\nMeanwhile the non-imaging competitor has already won the diagnostic question for Parkinson's. Seed amplification assays on cerebrospinal fluid are reported at 87.7% sensitivity and 96.3% specificity for Parkinson's in the PPMI cohort, with a pooled meta-analysis at 0.86 and 0.92. What the assay cannot do is say where in the brain the pathology is, or how much, or whether a drug reduced it, and it is markedly less reliable in multiple system atrophy. That is the residual space an imaging agent has.","asOf":"2026-09-23","links":[{"label":"[18F]ACI-12589 first-in-human, Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"label":"Conference report: signal only in multiple system atrophy","url":"https://www.alzforum.org/news/conference-coverage/first-field-synuclein-pet-only-multiple-system-atrophy"},{"label":"No approved small-molecule alpha-synuclein PET agent","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13121216/"},{"label":"Seed amplification assays: past, present and future roles","url":"https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm"},{"label":"Pooled meta-analysis of alpha-synuclein seed amplification assays","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12192484/"}],"tags":["unmet need first","neurology","worked negative","pharmacodynamic marker"],"related":["f-18","tau-protein","amyloid-beta"],"indications":["parkinsonian-syndromes"],"sections":[],"technologies":["pet","pet-ct"],"targets":["alpha-synuclein","dopamine-transporter"],"drugs":["i-123-ioflupane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"There is no way to see pathological alpha-synuclein in a living brain, so ambiguous parkinsonian syndromes cannot be told apart at the molecular level and no anti-alpha-synuclein drug can demonstrate that it engaged its target.","useCase":"The credible use today is inside drug development: measuring regional target load and its change on treatment in an anti-alpha-synuclein trial, and enriching multiple system atrophy cohorts. A clinical differential-diagnosis use would require sensitivity in Parkinson's disease that the leading tracer does not yet have.","hypothesis":"A next-generation alpha-synuclein tracer with higher affinity for Lewy-type aggregates will detect the lower-density, more diffuse pathology of Parkinson's disease that [18F]ACI-12589 misses, and will thereby provide the regional quantification that a cerebrospinal fluid assay cannot.","rationale":"The target is the defining pathology of a large disease group, and the precedent is exact: amyloid and tau agents were approved on the basis of visual and quantitative correspondence with post-mortem pathology, which is the same claim structure an alpha-synuclein agent would make. The first-generation tracer proves the concept is reachable, because it does separate multiple system atrophy from controls. Against that, its failure in Parkinson's is the central obstacle, and it appears to be a density and affinity problem rather than a specificity one, since the same tracer binds Parkinson's tissue post mortem.","test":"A head-to-head study in patients with a positive cerebrospinal fluid seed amplification assay, comparing a next-generation tracer's regional binding against the assay result and against clinical diagnosis, powered to detect Parkinson's disease against controls. The tracer must clear the bar that the current agent failed: a measurable signal in Parkinson's, not only in multiple system atrophy.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"[18F]ACI-12589 (also [18F]MNI-1216) from AC Immune, first-in-human complete under NCT06445465 with a 42-participant validation cohort published in Nature Communications 2023; it separates multiple system atrophy from controls but shows limited binding in Parkinson's disease.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"Alpha-synuclein aggregation defines Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, and the tracer binds post-mortem tissue from all of them; the in-vivo failure is one of aggregate density, not of target validity.","source":"Nature Communications 2023 and Alzforum conference report","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/","weighted":true},{"domain":"clinical-evidence","state":"thin","why":"One published 42-participant cohort from one tracer, plus a completed phase 1; no agent has reached a pivotal or registrational trial and no FDA-approved alpha-synuclein PET agent exists.","source":"Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"domain":"diagnostic-performance","state":"thin","why":"Binding separates multiple system atrophy from controls and from other neurodegenerative disorders, but is limited in Parkinson's disease, which is the population that would generate most of the demand.","source":"Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No serious safety signal has been reported in the small published cohorts, but no independently verified dosimetry table for the leading agent was found."},{"domain":"regulatory-path","state":"moderate","why":"A precedent exists for approving an intracellular-aggregate PET agent: flortaucipir F-18 and the amyloid agents were approved on correspondence with pathology rather than on a treatment-selection claim.","source":"FDA label, flortaucipir F-18","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212123s000lbl.pdf"}],"flags":[{"category":"technical","flag":"red","why":"The leading fluorine-18 tracer gives no detectable signal in Parkinson's disease in vivo despite binding the tissue post mortem; that is the whole technical problem and it is unsolved."},{"category":"unmet-need","flag":"amber","why":"The diagnostic need is real but partly met: a cerebrospinal fluid assay reaches 87.7% sensitivity and 96.3% specificity for Parkinson's, leaving imaging the regional and pharmacodynamic questions."},{"category":"ip","flag":"amber","why":"The leading chemical series belongs to AC Immune; several academic and company programmes are chasing new scaffolds."},{"category":"commercial","flag":"red","why":"Companion-only in practice, and no anti-alpha-synuclein therapy is approved; prasinezumab did not separate from placebo on the primary endpoint of its phase 2."},{"category":"isotope","flag":"green","why":"Fluorine-18, the most distributable PET isotope."},{"category":"competition","flag":"amber","why":"Several groups are pursuing new scaffolds and the cerebrospinal fluid assay is already in wide research use, so a tracer must beat a cheap incumbent on a narrower question."}],"competition":[{"name":"AC Immune SA with Invicro","what":"[18F]ACI-12589 / [18F]MNI-1216, first-in-human complete, 42-participant published cohort; works in multiple system atrophy, limited in Parkinson's.","stage":"phase 1 complete","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"name":"Seed amplification assay developers","what":"Cerebrospinal fluid alpha-synuclein seed amplification, reported at 87.7% sensitivity and 96.3% specificity for Parkinson's in the PPMI cohort.","stage":"in research and clinical use","url":"https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm"}],"differentiation":"A seed amplification assay answers whether seed-competent alpha-synuclein is present anywhere, cheaply and with high accuracy in Parkinson's; it does not localise, quantify, or track change, and is markedly less reliable in multiple system atrophy. An imaging agent that only matched the assay's diagnostic accuracy would not be worth its cost; one that measured regional load and its change on treatment would be.","metrics":[{"label":"Participants in the published [18F]ACI-12589 in-vivo cohort","value":"42, including 13 with multiple system atrophy and 8 with Parkinson's","source":"Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"label":"Cerebrospinal fluid seed amplification assay accuracy for Parkinson's in the PPMI cohort","value":"87.7% sensitivity, 96.3% specificity","source":"Reported from the PPMI Lancet Neurology analysis","url":"https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm"},{"label":"Pooled seed amplification assay sensitivity and specificity across biomatrices","value":"0.86 and 0.92","source":"Pooled meta-analysis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12192484/"}],"risks":["Lewy-type aggregate density in Parkinson's disease may simply be below what PET can resolve, in which case no affinity improvement rescues the indication.","Without an approved anti-alpha-synuclein therapy there is no companion market, and the leading antibody missed its phase 2 primary endpoint.","The cerebrospinal fluid assay is cheap, accurate for Parkinson's and already adopted in research, which caps what an imaging agent can claim."],"watch":["Any tracer reporting a measurable Parkinson's-versus-control difference in vivo, which is the single result that would change this record.","Longitudinal multiple system atrophy studies with the current agent, which could establish a progression biomarker even without a Parkinson's claim.","Anti-alpha-synuclein therapeutic readouts, since a companion agent needs a drug to accompany."],"route":"/opportunities/opp-alpha-synuclein-pet-parkinsons/"}
{"id":"opp-fap-pancreatic-staging","kind":"opportunity","name":"FAP imaging to stop futile pancreatic surgery","aka":["FAPI PET in PDAC"],"tldr":"Four in ten pancreatic cancer patients whose scans say the tumour can be removed turn out, once opened up, to have disease that cannot be removed. A scan that lights up the scar tissue around tumour deposits sees more of that hidden disease than the standard one.","summary":"The number that defines this opportunity comes from a Cochrane review: the median pre-test probability of unresectable disease after CT was 41.4%, meaning 41 of 100 participants whose cancer looked resectable on CT were found unresectable at laparotomy. The operation that follows is major surgery with no curative benefit.\n\nFAP imaging attacks that gap directly, because pancreatic ductal adenocarcinoma is a stroma-rich tumour and the tracer reports the fibroblast compartment rather than glucose uptake. A 62-patient prospective study of 18F-FAPI-04 against FDG upgraded the TNM stage in 14 patients, with higher uptake in primary tumours, nodes, liver and peritoneal deposits, and FDG missed one patient with cancer that FAPI found. A PDAC-specific meta-analysis of 7 studies and 322 patients gives pooled sensitivity of 0.99 against 0.84 for FDG with comparable specificity. A 20-patient Korean study found FAPI-74 detected metastatic nodes in 50% of cases against 0% for FDG.\n\nThe gap in the evidence is precise and worth stating: no trial has yet reported that FAPI-based selection reduces the non-curative laparotomy rate. The completed SOFIE phase 2 (NCT05262855, 63 patients) measured sensitivity against histopathology, not operations avoided. On the therapy side the picture is discouraging — FRONTIER was terminated early for rapid clearance and low tumour doses, and across eight compassionate-use patients the predominant outcome was radiological progression — which strengthens the case for treating this as a diagnostic opportunity rather than a theranostic one.","asOf":"2026-09-23","links":[{"label":"Cochrane review: unresectable disease found at laparotomy after CT","url":"https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd009323.pub3/full"},{"label":"18F-FAPI-04 against FDG in 62 patients, J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/jnumed/65/2/206.full.pdf"},{"label":"NCT05262855: [68Ga]FAPI-46 phase 2 in pancreatic cancer","url":"https://clinicaltrials.gov/study/NCT05262855"},{"label":"[18F]AlF-FAPI-74 in potentially resectable pancreatic cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11634952/"},{"label":"FRONTIER terminated early for rapid clearance","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12607575/"}],"tags":["unmet need first","pancreas","surgical selection","stroma"],"related":["ga-68","f-18","lu-177"],"indications":["pancreatic-cancer"],"sections":[],"technologies":["fapi-pet","pet-ct","fdg-pet"],"targets":["fap"],"drugs":["ga-68-fapi-46","fap-2286"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"No validated test tells a pancreatic tumour board, before operating, whether a CT-resectable tumour hides peritoneal or small liver metastases, and 41.4% of CT-resectable patients are found unresectable at laparotomy.","useCase":"A hepatobiliary surgeon and tumour board would scan every patient considered for resection or for neoadjuvant therapy, and would cancel or defer surgery on the strength of peritoneal or hepatic deposits that CT cannot see. The endpoint that matters is operations not performed.","hypothesis":"FAP-directed PET before pancreatic resection will identify CT-occult peritoneal and hepatic metastases often enough to reduce the non-curative laparotomy rate below the 41.4% that follows CT staging alone.","rationale":"Pancreatic ductal adenocarcinoma is defined by its fibroblast-rich stroma, which is why a tracer aimed at fibroblast activation protein has repeatedly outperformed FDG in this disease specifically: pooled sensitivity 0.99 against 0.84 across 322 patients, stage upgraded in 14 of 62 patients in a prospective head-to-head, and peritoneal disease visible where FDG showed nothing. Multiple isotopes and constructs work, including fluorine-18 versions that can be distributed. The missing step is not proof of detection but proof of consequence.","test":"A prospective study in patients deemed resectable on CT, imaging all of them with a FAP tracer, with a pre-specified rule for when a FAPI-positive extra-pancreatic finding cancels or alters surgery, and the primary endpoint being the non-curative laparotomy rate against the 41.4% historical benchmark. Histology or laparoscopy must confirm every scan-positive finding that changes management.","maturity":"being-tested-at-scale","verdict":"standalone-and-companion","mostAdvanced":"[68Ga]FAPI-46 from SOFIE: a completed prospective multicentre phase 2 in resectable or borderline resectable pancreatic ductal adenocarcinoma, 63 patients, with histopathology as truth standard (NCT05262855). On the therapy side, 177Lu-FAP-2286 in Novartis's LuMIERE phase 1/2 (NCT04939610).","dueDiligence":[{"domain":"target-biology","state":"strong","why":"Pancreatic ductal adenocarcinoma is stroma-rich and fibroblast activation protein is expressed in the tumour stroma rather than the tumour cells, which is why uptake exceeds FDG in primary tumours, nodes and peritoneal deposits.","source":"Wang et al., J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/jnumed/65/2/206.full.pdf","weighted":true},{"domain":"clinical-evidence","state":"strong","why":"A completed prospective multicentre phase 2 of 63 patients with histopathology truth standard, a 62-patient prospective head-to-head against FDG, a 20-patient resectability cohort, and a PDAC-specific meta-analysis of 7 studies and 322 patients.","source":"NCT05262855 and Hu et al. meta-analysis","url":"https://clinicaltrials.gov/study/NCT05262855","weighted":true},{"domain":"diagnostic-performance","state":"strong","why":"Pooled sensitivity 0.99 (0.97 to 1.00) for FAPI against 0.84 (0.70 to 0.92) for FDG with comparable specificity across 322 patients; stage upgraded in 14 of 62 patients in a prospective comparison.","source":"PDAC-specific meta-analysis, Academic Radiology 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12890629/","weighted":true},{"domain":"safety-dosimetry","state":"moderate","why":"Diagnostic FAPI agents have been used across many published cohorts without reported safety signals; on the therapeutic side whole-body effective dose for 177Lu-FAPI-XT was 0.039 plus or minus 0.013 Sv/GBq.","source":"Phase 1 dose escalation report","url":"https://pubmed.ncbi.nlm.nih.gov/41087606/"},{"domain":"regulatory-path","state":"thin","why":"No FAP imaging agent is approved anywhere, and no trial has yet used a management endpoint such as avoided laparotomy, which is the claim this opportunity actually needs.","source":"NCT05262855 primary outcome","url":"https://clinicaltrials.gov/study/NCT05262855"}],"flags":[{"category":"technical","flag":"green","why":"Works with both gallium-68 and fluorine-18 constructs, same-day imaging, and repeatedly reproduced across independent centres."},{"category":"unmet-need","flag":"green","why":"A 41.4% futile-laparotomy rate after CT staging is a large, quantified, guideline-recognised failure of current imaging."},{"category":"ip","flag":"red","why":"The FAPI chemical space is crowded with FAPI-04, FAPI-46, FAPI-74, FAP-2286 and numerous derivatives across multiple sponsors and academic groups."},{"category":"commercial","flag":"green","why":"Standalone: the value is surgery avoided, which needs no drug approval, and a FAP-directed therapy would be an additional rather than a necessary use."},{"category":"isotope","flag":"green","why":"Gallium-68 and fluorine-18 both established; the therapeutic side would need lutetium-177 or an alpha emitter."},{"category":"competition","flag":"red","why":"A completed multicentre phase 2 exists, Novartis holds the leading therapeutic, and numerous academic groups publish in this space."}],"competition":[{"name":"SOFIE Biosciences","what":"[68Ga]FAPI-46 phase 2 in resectable and borderline resectable pancreatic ductal adenocarcinoma, 63 patients, completed, histopathology truth standard.","stage":"phase 2 complete","url":"https://clinicaltrials.gov/study/NCT05262855"},{"name":"Novartis","what":"177Lu-FAP-2286 in LuMIERE, phase 1/2, 222 planned; phase 1 had 27 patients including 9 with pancreatic cancer, with one partial response and nine stable.","stage":"phase 1/2","url":"https://clinicaltrials.gov/study/NCT04939610"},{"name":"Chinese and Korean academic groups","what":"18F-FAPI-04 in 62 patients prospectively against FDG, and [18F]AlF-FAPI-74 in 20 potentially resectable patients.","stage":"published prospective studies","url":"https://jnm.snmjournals.org/content/jnumed/65/2/206.full.pdf"},{"name":"POINT Biopharma","what":"177Lu-PNT6555 in FRONTIER, terminated early because rapid clearance gave low tumour absorbed doses and limited efficacy.","stage":"terminated","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12607575/"}],"differentiation":"The comparators are CT, which leaves a 41.4% futile-laparotomy rate, and staging laparoscopy, which is itself an operation. CA 19-9 is neither sensitive nor specific enough to decide resectability, and FDG PET is not standard in this disease. FAP imaging is differentiated because pancreatic cancer is the tumour where the stromal target is most abundant and FDG performs worst.","metrics":[{"label":"CT-resectable patients found unresectable at laparotomy","value":"41.4% median pre-test probability","source":"Cochrane review, Allen et al. 2016","url":"https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.cd009323.pub3/full"},{"label":"Pooled sensitivity of FAPI against FDG in pancreatic ductal adenocarcinoma","value":"0.99 against 0.84 across 7 studies and 322 patients","source":"Hu et al., Academic Radiology 2025, via review","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12890629/"},{"label":"Patients whose TNM stage was upgraded by 18F-FAPI-04 against FDG","value":"14 of 62","source":"Wang et al., J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/jnumed/65/2/206.full.pdf"},{"label":"Metastatic lymph node detection, FAPI-74 against FDG","value":"50% against 0% of 10","source":"20-patient prospective cohort","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11634952/"}],"risks":["FAP is expressed in wound healing, pancreatitis and other fibrotic conditions, so specificity in a chronically inflamed pancreas is the obvious failure mode and needs its own dataset.","Detection superiority does not automatically translate into fewer futile operations; a surgeon will not cancel an operation on an unbiopsied peritoneal signal without prospective evidence.","The therapeutic side of FAP is going badly, with one terminated trial and mostly progression in compassionate use, so a theranostic pitch would be weak."],"watch":["Publication of the SOFIE phase 2 results and whether any follow-on trial adopts avoided laparotomy as an endpoint.","Specificity data in chronic pancreatitis and post-treatment fibrosis, which is where this agent will either hold up or fail.","Whether FAP-directed therapy recovers after FRONTIER, which determines if a companion use ever exists."],"route":"/opportunities/opp-fap-pancreatic-staging/"}
{"id":"opp-cardiac-sarcoidosis-specific-tracer","kind":"opportunity","name":"An inflammation tracer that does not need a diet","aka":["SSTR PET in cardiac sarcoidosis"],"tldr":"Deciding whether to put a patient on long-term steroids for heart sarcoidosis depends on a scan that only works if the patient's heart has been starved of sugar for a day, and a biopsy that misses the disease most of the time. A different tracer would not need the diet.","summary":"Cardiac sarcoidosis is the case where the incumbent test's weakness is procedural rather than biological. FDG PET requires metabolic suppression of normal myocardium through a strict low-carbohydrate, high-fat preparation, and imperfect suppression produces false positives on which immunosuppression decisions are then made. The histological reference standard is worse: endomyocardial biopsy sensitivity is reported at approximately 20 to 30%, and elsewhere as less than 25%. There is no reliable serum biomarker for diagnosis, monitoring of inflammatory activity or severity. And the disease is substantially under-recognised: about 5% of sarcoidosis patients have clinically manifest cardiac involvement while autopsy series report 25% to 50%.\n\nSomatostatin receptor tracers are the most developed alternative because macrophages in active granulomas express SSTR2, and no dietary preparation is needed. The evidence is consistent but small and mixed. A University of Pennsylvania study of 11 patients found 91% patient-level concordance with FDG but only 77.1% segment-level agreement, a lower signal-to-blood-pool ratio of 3.2 against 4.9, and underestimation of treatment response. A Würzburg 68Ga-DOTATOC study of 15 patients found SSTR-PET positive in 7 of 15 against cardiac MRI in 10 of 15. A 19-patient comparative study of 68Ga-DOTANOC has been reported at 100% diagnostic accuracy against 79% for FDG, while a 17-patient study found poorer agreement with MRI at 76.5%.\n\nThe practical attraction is that the tracer itself is already approved for another indication as NETSPOT, so manufacturing and dosimetry are de-risked; what is missing is a clinical package for this indication, and a completed 78-patient Swedish study with biopsy and MRI comparators is the largest dataset that could supply one.","asOf":"2026-09-23","links":[{"label":"68Ga-DOTATATE against FDG in cardiac sarcoidosis, J Nucl Cardiol 2023","url":"https://link.springer.com/article/10.1007/s12350-022-03111-4"},{"label":"NCT04206163: somatostatin receptor imaging in inflammatory heart disease, 78 patients","url":"https://clinicaltrials.gov/study/NCT04206163"},{"label":"No reliable serum biomarker in sarcoidosis, JACC state-of-the-art review","url":"https://www.jacc.org/doi/10.1016/j.jacc.2020.08.042"},{"label":"Clinically manifest against autopsy prevalence, JAHA 2023","url":"https://www.ahajournals.org/doi/10.1161/JAHA.122.028342"},{"label":"68Ga-DOTATOC compared with cardiac MRI, Oncotarget 2016","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5363622/"}],"tags":["unmet need first","cardiac","non-oncology","inflammation"],"related":["ga-68","f-18"],"indications":["cardiac-sarcoidosis"],"sections":[],"technologies":["sstr-pet","fdg-pet","pet-ct"],"targets":["sstr2"],"drugs":["ga68-dotatate","fludeoxyglucose-f18","ga-68-dotatoc"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"unmet-need-first","unmetNeed":"No non-invasive test reliably establishes whether myocardial inflammation is active right now, because FDG PET depends on imperfect dietary suppression, endomyocardial biopsy has sensitivity of roughly 20 to 30%, and no serum biomarker exists.","useCase":"A cardiologist would use it to decide whether to start or continue immunosuppression in suspected cardiac sarcoidosis, and to judge response on treatment, in the specific patients where FDG preparation has failed or is impractical, such as those with diabetes.","hypothesis":"A somatostatin-receptor or other macrophage-directed tracer will identify active cardiac sarcoidosis with accuracy at least equal to well-prepared FDG PET while removing the dietary preparation, and will therefore give a reliable answer in the patients where FDG currently fails.","rationale":"Activated macrophages in sarcoid granulomas express somatostatin receptor 2, so there is a specific target for active inflammation rather than a metabolic surrogate. The tracer is already manufactured and approved for neuroendocrine tumour imaging, which removes most chemistry and dosimetry risk. Five independent cohorts have imaged cardiac sarcoidosis patients with SSTR agents and all reported detectable disease. Against that, the Pennsylvania study found a lower signal-to-background ratio than FDG and underestimation of treatment response, and the segment-level agreement of 77.1% is not good enough to guide focal management.","test":"A prospective multicentre study in suspected cardiac sarcoidosis, imaging every patient with both an SSTR tracer and correctly prepared FDG PET, with cardiac MRI and where available endomyocardial biopsy as comparators, and a pre-specified analysis of the subgroup in which FDG suppression failed. The endpoint that matters is agreement with the final adjudicated diagnosis and with treatment response, not agreement with FDG.","maturity":"early-clinical","verdict":"standalone-only","mostAdvanced":"68Ga-DOTATATE and related SSTR ligands used off-label in completed academic studies: 11 patients at the University of Pennsylvania (NCT03746847), 15 at Mayo Clinic (NCT03549598) and 78 in a completed Swedish study of inflammatory heart disease (NCT04206163). No agent is near filing for this indication.","dueDiligence":[{"domain":"target-biology","state":"moderate","why":"Activated macrophages in sarcoid granulomas express somatostatin receptor 2, giving a specific inflammation target, but signal-to-blood-pool ratio was lower than FDG at 3.2 plus or minus 0.6 against 4.9 plus or minus 1.5.","source":"Lee et al., J Nucl Cardiol 2023","url":"https://link.springer.com/article/10.1007/s12350-022-03111-4","weighted":true},{"domain":"clinical-evidence","state":"thin","why":"Five small cohorts, the largest a completed 78-patient Swedish study that also enrolled myocarditis; the published cardiac sarcoidosis series are 11, 15, 17 and 19 patients.","source":"NCT04206163","url":"https://clinicaltrials.gov/study/NCT04206163"},{"domain":"diagnostic-performance","state":"moderate","why":"Patient-level concordance with FDG was 91% but segment-level agreement only 77.1% with kappa 0.53; one 19-patient study reported 100% accuracy against 79% for FDG, while a 17-patient study found only 76.5% agreement with MRI.","source":"Lee et al. 2023 and comparative reviews","url":"https://ajronline.org/doi/10.2214/AJR.20.22790","weighted":true},{"domain":"safety-dosimetry","state":"strong","why":"The tracer is approved as NETSPOT for neuroendocrine tumour localisation, so its manufacturing, safety and dosimetry package already exists; only the cardiac indication is off-label.","source":"FDA label, NETSPOT","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208547s024lbl.pdf"},{"domain":"regulatory-path","state":"thin","why":"No SSTR agent has a cardiac sarcoidosis indication and none has filed for one; the route would be a new indication on an approved molecule, judged against FDG PET and adjudicated diagnosis.","source":"FDA label, NETSPOT","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208547s024lbl.pdf"}],"flags":[{"category":"technical","flag":"amber","why":"No dietary preparation is the whole point, but the published signal-to-blood-pool ratio is lower than FDG and treatment response was underestimated in the largest concordance study."},{"category":"unmet-need","flag":"green","why":"An immunosuppression decision currently rests on a diet-dependent scan and a biopsy with roughly 20 to 30% sensitivity, with no serum biomarker of any kind."},{"category":"ip","flag":"red","why":"The leading agents are approved generic-era somatostatin ligands; there is no proprietary position to take in DOTATATE itself."},{"category":"commercial","flag":"amber","why":"Standalone and repeatable for treatment monitoring, but cardiac sarcoidosis is a small indication and the tracer is already purchasable for another one, so a sponsor would fund a trial for a label it may not be able to protect."},{"category":"isotope","flag":"green","why":"Gallium-68 from a generator, already distributed for neuroendocrine imaging."},{"category":"competition","flag":"amber","why":"The competition is off-label use of an approved tracer, which is cheap and available now and therefore hard to displace with a funded programme."}],"competition":[{"name":"University of Pennsylvania","what":"68Ga-DOTATATE against FDG in 11 cardiac sarcoidosis patients with follow-up scans in 8; 91% patient-level concordance, 77.1% segment-level.","stage":"completed pilot","url":"https://link.springer.com/article/10.1007/s12350-022-03111-4"},{"name":"Mayo Clinic","what":"Phase 4 comparison of 68Ga-DOTATATE with FDG and 13N-ammonia PET/CT, 15 patients, completed.","stage":"completed","url":"https://clinicaltrials.gov/study/NCT03549598"},{"name":"Västra Götaland Region, Sweden","what":"68Ga-DOTA-TOC in inflammatory heart disease, 78 participants, against contrast MRI, FDG PET and endomyocardial biopsy; completed June 2024.","stage":"completed","url":"https://clinicaltrials.gov/study/NCT04206163"},{"name":"Würzburg and other academic groups","what":"68Ga-DOTATOC in 15 patients with biopsy-proven sarcoidosis and suspected cardiac involvement, positive in 7 of 15 against MRI in 10 of 15.","stage":"published feasibility","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5363622/"}],"differentiation":"There is presently no reliable serum biomarker for diagnosis, monitoring of inflammatory activity or severity in sarcoidosis, and cardiac MRI shows scar rather than current activity. The differentiation from FDG is entirely operational: no dietary preparation, and therefore an answer in patients whose suppression fails, including those with diabetes.","metrics":[{"label":"Patient-level and segment-level concordance of 68Ga-DOTATATE with FDG","value":"91% and 77.1% in 11 patients","source":"Lee et al., J Nucl Cardiol 2023","url":"https://link.springer.com/article/10.1007/s12350-022-03111-4"},{"label":"Endomyocardial biopsy sensitivity for cardiac sarcoidosis","value":"approximately 20 to 30%","source":"Published review","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8746035/"},{"label":"Clinically manifest against autopsy prevalence of cardiac involvement in sarcoidosis","value":"about 5% against 25 to 50%","source":"Sperry et al., JAHA 2023","url":"https://www.ahajournals.org/doi/10.1161/JAHA.122.028342"}],"risks":["The lower signal-to-blood-pool ratio and underestimated treatment response reported at Pennsylvania could make the agent worse than a well-prepared FDG scan rather than better.","Segment-level agreement of 77.1% is not adequate for guiding focal decisions such as device placement or ablation.","Because the tracer is already on the market for another indication, off-label use will absorb the clinical demand and nobody may fund the registrational study."],"watch":["Publication of the 78-patient Swedish study, which is the largest dataset and includes biopsy comparison.","Any macrophage-directed tracer with a better signal-to-background ratio than the somatostatin ligands, which is the specific weakness to beat.","Guideline language on alternatives to FDG when metabolic suppression fails, which would create the indication a sponsor could file against."],"route":"/opportunities/opp-cardiac-sarcoidosis-specific-tracer/"}
{"id":"opp-gpc3-hcc-china","kind":"opportunity","name":"GPC3 imaging of the indeterminate liver nodule, led from China","aka":["GPC3 PET","glypican-3 imaging"],"tldr":"Cirrhotic livers throw up nodules that scans cannot classify, and the usual answer is to wait three to six months to see if they grow. Several Chinese hospital programmes are testing tracers that recognise a protein carried by most liver cancers, and almost none of that work appears in Western pipeline reviews.","summary":"This record exists partly to demonstrate the non-US-registry lens. The clinical problem is well defined: using the CT/MRI LI-RADS algorithm, the pooled proportion of hepatocellular carcinoma is 31% for LR-3 and 64% for LR-4 observations, so a large share of nodules sit in categories that neither confirm nor exclude cancer, and the management default is serial imaging. Glypican-3 is overexpressed in 70 to 80% of hepatocellular carcinomas and virtually absent in normal adult liver and benign hepatic lesions, which is an unusually clean contrast for a liver target.\n\nThe programmes divide along geography. The most mature single dataset is Western: [68Ga]Ga-RAYZ-8009 from RayzeBio, now part of Bristol Myers Squibb, with a 24-patient first-in-human case series run in the Netherlands and Germany, no adverse events, and tumour-to-liver ratios averaging 8.3 at about an hour. A related investigator-initiated cohort in India reported 64 patients scanned with 92% showing at least one positive lesion. But the deepest programme is at Wuhan Union Hospital: 68Ga-XH06, an antibody-fragment immunoPET agent registered as NCT06383520 with 100 patients estimated, published as a 5-patient pilot in EJNMMI and an 8-patient first-in-human study in Clinical Cancer Research, with conference cohorts of 30 and 36 patients reporting sensitivity of 90.63% and specificity of 100% against pathology in one data cut and 91.7% and 83.3% in another. A head-to-head against enhanced MRI is registered at 150 patients, and a further 40-patient study is recruiting at Xiamen.\n\nNo GPC3 imaging agent has FDA, EMA or NMPA marketing approval. The point of the record is that a landscape review built only on ClinicalTrials.gov Western entries would see the 24-patient case series and miss the registered 100- and 150-patient Chinese studies behind it.","asOf":"2026-09-23","links":[{"label":"LI-RADS: pooled proportion of hepatocellular carcinoma by category, Radiology 2023","url":"https://pubs.rsna.org/doi/full/10.1148/radiol.222801"},{"label":"[68Ga]Ga-RAYZ-8009 first-in-human case series, J Nucl Med 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39362766/"},{"label":"NCT06383520: GPC3-targeted PET imaging in hepatocellular carcinoma, Wuhan","url":"https://clinicaltrials.gov/study/NCT06383520"},{"label":"NCT07352345: GPC3 PET against enhanced MRI, 150 patients","url":"https://clinicaltrials.gov/study/NCT07352345"},{"label":"GPC3-targeted immunoPET translational study, EJNMMI 2026","url":"https://pubmed.ncbi.nlm.nih.gov/41688850/"}],"tags":["non-US registry","liver","China","indeterminate nodule"],"related":["ga-68"],"indications":["hcc"],"sections":[],"technologies":["immuno-pet","pet-ct","pet-mri"],"targets":["gpc3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"non-us-registry","unmetNeed":"When a nodule in a cirrhotic liver is categorised LR-3 or LR-4, no test says whether it is cancer now, and the default is three to six months of serial imaging in a disease where delay costs the chance of curative treatment.","useCase":"A hepatologist or liver multidisciplinary team would scan the indeterminate nodule, or the patient with a rising suspicion and a normal alpha-fetoprotein, to decide immediately between ablation, resection, transplant listing and surveillance, rather than waiting for interval growth.","hypothesis":"A GPC3-directed PET agent will classify LR-3 and LR-4 liver observations correctly enough to replace the interval-growth wait, because the target is present in 70 to 80% of hepatocellular carcinomas and effectively absent from normal liver and benign lesions.","rationale":"The target contrast is the strongest part of the case: overexpression in 70 to 80% of tumours against virtual absence in normal adult liver and benign hepatic lesions, and published tumour-to-liver ratios averaging 8.3. Multiple independent groups have already imaged patients safely, one agent has detected roughly 1 cm intrahepatic metastases that MRI missed, and a registered head-to-head against enhanced MRI at 150 patients is the right comparator study. The pathology-referenced sensitivity figures from Wuhan, 90.63% with 100% specificity in one cut, are conference-level and need peer-reviewed publication before they can be relied on.","test":"A prospective study restricted to LI-RADS LR-3 and LR-4 observations, imaging each with a GPC3 tracer and following every patient to a definitive diagnosis by histology or 12-month imaging, with the primary endpoint being the proportion of indeterminate nodules correctly reclassified and the time to definitive management compared with the surveillance default. The registered 150-patient head-to-head against enhanced MRI is close to this design.","maturity":"early-clinical","verdict":"standalone-only","mostAdvanced":"[68Ga]Ga-RAYZ-8009 (RayzeBio, Bristol Myers Squibb) with a 24-patient first-in-human series in the Netherlands and Germany; the deepest programme is 68Ga-XH06 at Wuhan Union Hospital, registered as NCT06383520 at 100 patients with a 150-patient head-to-head against MRI registered as NCT07352345.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"Glypican-3 is a cell-surface heparan sulfate proteoglycan overexpressed in 70 to 80% of hepatocellular carcinomas yet virtually absent in normal adult liver and benign hepatic lesions.","source":"Filippi et al., Cancers 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12292357/","weighted":true},{"domain":"clinical-evidence","state":"moderate","why":"A 24-patient first-in-human series, a 64-patient investigator-initiated cohort in India, a peer-reviewed 5-patient and 8-patient Chinese series, and registered Chinese studies of 100 and 150 patients; none is registrational.","source":"Poot et al., J Nucl Med 2024; NCT06383520","url":"https://clinicaltrials.gov/study/NCT06383520","weighted":true},{"domain":"diagnostic-performance","state":"moderate","why":"Tumour-to-liver ratio averaged 8.3 at about one hour in the first-in-human series; conference cohorts report sensitivity 90.63% with specificity 100% in 36 patients and 91.7% with 83.3% in 30, both against pathology and both unpublished in full.","source":"SNMMI 2025 press release and J Nucl Med supplement","url":"https://snmmi.org/Web/Web/News/Articles/ImmunoPET-Tracer-Enhances-Early-Detection-of-Liver-Cancer.aspx","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No adverse events reported across the published cohorts, but no dosimetry in mSv or cGy/MBq was found for any of the newer gallium-68 GPC3 probes."},{"domain":"regulatory-path","state":"thin","why":"No GPC3-targeted imaging agent has received FDA, EMA or NMPA marketing approval, and no filing has been identified in any jurisdiction.","source":"Research review of approvals","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12292357/"}],"flags":[{"category":"technical","flag":"amber","why":"The Chinese lead is an antibody-fragment immunoPET agent and the Western lead a synthetic peptide; both image within about an hour, but liver background is the hardest part of this anatomy and the constructs differ in kinetics."},{"category":"unmet-need","flag":"green","why":"31% of LR-3 and 64% of LR-4 observations prove to be cancer, and the alternative to a decisive test is months of watching."},{"category":"ip","flag":"amber","why":"The peptide lead sits inside Bristol Myers Squibb after the RayzeBio acquisition and the antibody-fragment lead with a Chinese academic hospital; several other constructs are in early trials."},{"category":"commercial","flag":"green","why":"Standalone: the scan resolves a management dilemma by itself, in a disease that is a leading cause of cancer death worldwide, with the largest patient population in China."},{"category":"isotope","flag":"green","why":"Gallium-68 across all the leading agents."},{"category":"competition","flag":"amber","why":"At least five separate programmes have human data, split between Western peptide and Chinese antibody-fragment approaches, and none is close to filing."}],"competition":[{"name":"RayzeBio (Bristol Myers Squibb)","what":"[68Ga]Ga-RAYZ-8009, 24-patient first-in-human series in the Netherlands and Germany, no adverse events, mean tumour-to-liver ratio 8.3.","stage":"first-in-human","url":"https://pubmed.ncbi.nlm.nih.gov/39362766/"},{"name":"Union Hospital, Tongji Medical College (Wuhan)","what":"68Ga-XH06 immunoPET: NCT06383520 at 100 patients estimated, a registered 150-patient head-to-head against enhanced MRI, and published pilots of 5 and 8 patients.","stage":"early phase 1, recruiting","url":"https://clinicaltrials.gov/study/NCT06383520"},{"name":"All India Institute of Medical Sciences","what":"[68Ga]Ga-RYZ-GPC3 in 64 patients, with 92% showing at least one positive lesion.","stage":"investigator-initiated","url":"https://aacrjournals.org/cancerres/article/84/6_Supplement/2585/740458/"},{"name":"First Affiliated Hospital of Xiamen University","what":"68Ga-GPC3 PET/CT against contrast-enhanced MRI, 40 patients estimated, recruiting.","stage":"recruiting","url":"https://clinicaltrials.gov/study/NCT07677774"}],"differentiation":"Alpha-fetoprotein misses a substantial share of hepatocellular carcinoma and does not localise; contrast-enhanced MRI is the incumbent and is exactly what leaves LR-3 and LR-4 undecided; biopsy of a small nodule in a cirrhotic liver carries bleeding and seeding risk and is often deferred. A GPC3 tracer competes with the decision to wait.","metrics":[{"label":"Proportion of LI-RADS observations that prove to be hepatocellular carcinoma","value":"31% of LR-3 and 64% of LR-4","source":"Cerny et al., Radiology 2023","url":"https://pubs.rsna.org/doi/full/10.1148/radiol.222801"},{"label":"Hepatocellular carcinomas overexpressing glypican-3","value":"70 to 80%","source":"Filippi et al., Cancers 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12292357/"},{"label":"Patients in the first-in-human [68Ga]Ga-RAYZ-8009 series","value":"24, no adverse events","source":"Poot et al., J Nucl Med 2024","url":"https://pubmed.ncbi.nlm.nih.gov/39362766/"},{"label":"Sensitivity and specificity of 68Ga-XH06 against pathology in the 36-patient conference cohort","value":"90.63% and 100%","source":"SNMMI 2025 abstract 252173, reported in a society press release","url":"https://snmmi.org/Web/Web/News/Articles/ImmunoPET-Tracer-Enhances-Early-Detection-of-Liver-Cancer.aspx"}],"risks":["The strongest accuracy figures are conference abstracts from overlapping cohorts at one hospital, and the exact patient overlap between the 5, 8, 30 and 36-patient reports is not stated in any source.","Around 20 to 30% of hepatocellular carcinomas do not overexpress glypican-3, so a negative scan cannot exclude cancer and the test would have to be positioned as a rule-in test only.","No dosimetry has been published for the newer gallium-68 constructs."],"watch":["Results from the registered 150-patient head-to-head against enhanced MRI, which is the study that would establish a clinical claim.","Whether Bristol Myers Squibb advances RAYZ-8009 beyond a case series, which would signal industry conviction.","Peer-reviewed publication of the 30 and 36-patient Wuhan cohorts, which currently exist only as conference abstracts."],"route":"/opportunities/opp-gpc3-hcc-china/"}
{"id":"f-18-naf","kind":"drug","name":"Sodium fluoride F-18","aka":["18F-NaF","Na18F","Fluoride F-18"],"tldr":"A radioactive form of fluoride that collects in areas of bone rebuilding. A PET scan after the injection shows those hot spots, which can be cancer that has spread to bone or something harmless like a healed fracture.","summary":"Sodium fluoride F-18 is one of the oldest PET radiopharmaceuticals: it was first approved by FDA in 1972 (NDA 17-042, held by the predecessor of GE Healthcare) as a bone-imaging agent, then re-approved under a newer label format in 2011 (NDA 22-494, sponsor National Cancer Institute) after the original product had lapsed commercially. Both approvals cover PET imaging of bone to define areas of altered osteogenic activity; neither approval is oncology-specific, but the agent's principal modern use is detecting osteoblastic bone metastases, most often from prostate and breast cancer, where it offers higher sensitivity and better spatial resolution than technetium-99m bone scintigraphy.\n\nThe recommended adult dose is 300-450 MBq (8-12 mCi) intravenously, with imaging optimally at one to two hours; no adverse reactions have been established in the FDA label, and the main safety statement concerns cumulative radiation exposure rather than a pharmacological toxicity. Because uptake is a marker of bone turnover, not malignancy, degenerative disease, fracture healing and other benign remodelling can be false positives, and correlation with CT or MRI is standard practice.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Sodium Fluoride F 18 Injection (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d867a881-108e-41fa-91ab-dc4df00cbb55"},{"label":"FDA approval letter, NDA 22-494 (2011)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022494Orig1s000Approv.pdf"}],"tags":["bone imaging","PET","generic"],"related":["f-18","tc-99m"],"indications":["prostate"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"Fluoride ion exchanges with hydroxyl groups on the hydroxyapatite crystal surface of bone, concentrating wherever bone turnover (osteoblastic activity) is high. Uptake reflects blood flow and new bone formation rather than tumour cells directly, so it lights up both malignant and benign remodelling.","approvals":[{"region":"US","year":1972,"indication":"Diagnostic PET imaging of bone to define areas of altered osteogenic activity (NDA 17-042)"},{"region":"US","year":2011,"indication":"Diagnostic PET imaging of bone to define areas of altered osteogenic activity (NDA 22-494, current labelling)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"300-450 MBq (8-12 mCi) in adults; imaging can begin 1-2 hours after administration, optimally at one hour","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d867a881-108e-41fa-91ab-dc4df00cbb55"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-naf/"}
{"id":"ga-68-fapi-46","kind":"drug","name":"Gallium-68 FAPI-46","aka":["68Ga-FAPI-46","Ga-68 FAPi-46"],"tldr":"An experimental PET tracer that lights up the scaffolding cells cancers build around themselves, not the cancer cells directly. It is still being tested, not yet an approved medicine.","summary":"68Ga-FAPI-46 is one of the most advanced compounds in the FAPI family under joint development by SOFIE Biosciences and GE HealthCare (global licence signed 2024). It has been studied prospectively in several hundred patients across breast, colorectal, pancreatic, head and neck, and other solid tumours. In a single-centre phase 2 trial at University Hospital Essen (NCT05160051, 155 patients scanned, reported in Lancet Oncology 2025), the tracer's positive predictive value for detecting immunohistochemically FAP-positive tumours was 90% on a per-patient basis and 92% per region, meeting the trial's pre-specified threshold.\n\nSeparate US phase 2 studies are running in resectable or borderline-resectable pancreatic ductal adenocarcinoma (NCT05262855/NCT05518903) across Mayo Clinic, UCLA, NYU Langone and BAMF Health, comparing FAPI-46 PET detection of cancer-associated fibroblasts against surgical histopathology, with phase 3 planning under way as of mid-2024. The tracer is not marketed anywhere; it is supplied under investigational new drug exemptions, and adverse events reported so far have been mild and mostly unrelated to the drug (5 of 90 adverse events in the Essen trial were judged possibly related, none serious).","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Pabst et al., Lancet Oncology 2025: 68Ga-FAPI-46 PET accuracy for cancer imaging with histopathology validation (phase 2 trial)","url":"https://pubmed.ncbi.nlm.nih.gov/40774265/"},{"label":"ClinicalTrials.gov NCT05160051 (68Ga-FAPI-46 PET for imaging of FAP-expressing cancer)","url":"https://clinicaltrials.gov/study/NCT05160051"},{"label":"ClinicalTrials.gov NCT05518903 (68Ga-FAPI-46 PET/CT for localised pancreatic ductal adenocarcinoma)","url":"https://clinicaltrials.gov/study/NCT05518903"}],"tags":["FAP","stroma","investigational"],"related":["ga-68"],"indications":["pancreatic-net","nsclc"],"sections":[],"technologies":["fapi-pet","pet-ct"],"targets":["fap"],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A quinoline-based fibroblast activation protein (FAP) inhibitor labelled with gallium-68. It binds tightly and is largely internalised by FAP-expressing cancer-associated fibroblasts in the tumour stroma, which surround the actual cancer cells in most solid epithelial tumours; the label therefore highlights the stromal reaction to a tumour rather than the tumour cells themselves.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ga-68-fapi-46/"}
{"id":"ga-68-pentixafor","kind":"drug","name":"Gallium-68 pentixafor","aka":["68Ga-Pentixafor","Gallium (68Ga) boclatixafortide"],"tldr":"An experimental PET tracer that looks for a specific docking protein (CXCR4) that some blood cancers and a minority of solid tumours carry in excess. It is a research tool, not an approved scan.","summary":"68Ga-Pentixafor has been used in over 1,300 patients across more than 75 publications, mostly at academic centres (Memorial Sloan Kettering, Technical University of Munich, and others) under investigator INDs, with no serious adverse events reported to date. Its clearest oncology signal is in multiple myeloma, indolent lymphomas and myeloproliferative neoplasms, where CXCR4 overexpression on malignant plasma cells or lymphocytes gives high image contrast; a first proof-of-principle study in myeloproliferative neoplasms found bone-marrow SUVmean of 6.45 versus 4.44 in healthy controls.\n\nIn solid tumours the picture is more mixed: a retrospective series of 142 patients across 23 histologies found discernible CXCR4 uptake above blood pool in only 68% of scans, indicating that receptor expression is present but inconsistent outside the haematological setting. Beyond oncology, the tracer is also being explored for primary aldosteronism lateralisation and unstable atherosclerotic plaque, reflecting CXCR4's broader role in inflammation. It has not been submitted for marketing approval anywhere and remains supplied through academic radiopharmacies under IND/IMPD exemptions.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Advances in PET imaging of the CXCR4 receptor, Seminars in Nuclear Medicine 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10792730/"},{"label":"CXCR4-directed PET/CT with 68Ga-pentixafor in solid tumours (142 patients), 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10957681/"}],"tags":["CXCR4","myeloma","investigational"],"related":["ga-68"],"indications":[],"sections":[],"technologies":["pet"],"targets":["cxcr4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A cyclic peptide analogue of the chemokine CXCL12, radiolabelled with gallium-68, that binds the chemokine receptor CXCR4. CXCR4 is upregulated on the surface of several haematological cancers (multiple myeloma, lymphomas, myeloproliferative neoplasms) and, less consistently, in solid tumours, so uptake marks tissue with high receptor density.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ga-68-pentixafor/"}
{"id":"cu-64-dotatate","kind":"drug","name":"Copper-64 dotatate","aka":["64Cu-DOTATATE","Detectnet"],"tldr":"An injectable tracer that sticks to a marker (somatostatin receptor) many neuroendocrine tumours carry. A PET scan afterwards shows where those tumours are, including small deposits that other scans can miss.","summary":"Detectnet (copper Cu 64 dotatate injection) was approved by FDA on 3 September 2020 under NDA 213227, sponsored by RadioMedix and commercialised by Curium, for use with PET to localise somatostatin-receptor-positive neuroendocrine tumours in adults. Approval rested on a US phase 3, reader-masked trial in 63 subjects (42 with known or suspected NETs, 21 healthy volunteers) run by Ebrahim Delpassand and colleagues, which found a diagnostic dose of 148 MBq (4 mCi) gave 100% sensitivity and 96.8% specificity after correcting an initial standard-of-truth misread, with excellent inter-reader agreement and no drug-related serious adverse events.\n\nCopper-64's longer half-life is the main practical advantage over the older gallium-68 tracers (NETSPOT/Ga-68 DOTATATE, Ga-68 DOTATOC): it permits central manufacture and next-day-style logistics, and its lower positron energy gives comparable or slightly better spatial resolution. Reported adverse reactions in the label are nausea, vomiting and flushing, with no listed contraindications. The recommended dose is 148 MBq (4 mCi) IV, with imaging roughly an hour later.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Detectnet (copper Cu 64 dotatate injection)","url":"https://www.accessdata.fda.gov/Drugsatfda_Docs/Label/2020/213227s000lbl.Pdf"},{"label":"FDA approval letter, NDA 213227 (2020)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213227Orig1s000Approv.pdf"},{"label":"Delpassand et al., J Nucl Med 2020: 64Cu-DOTATATE PET/CT pivotal phase 3 trial","url":"https://pubmed.ncbi.nlm.nih.gov/31924723/"}],"tags":["SSTR2","NET imaging","copper-64"],"related":["ga68-dotatate","ga-68-dotatoc","ga-68","cu-64"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":["sstr-pet","pet-ct"],"targets":["sstr2"],"drugs":[],"companies":["radiomedix","curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Detectnet","modality":"PET tracer","mechanism":"DOTATATE is a somatostatin analogue peptide that binds somatostatin receptor subtype 2 (SSTR2), which is overexpressed on most well-differentiated neuroendocrine tumour cells. Labelling it with copper-64 rather than gallium-68 gives a longer physical half-life (12.7 hours versus 68 minutes), which lets a single cyclotron batch supply multiple patients and imaging sites over the course of a working day without an on-site generator.","approvals":[{"region":"US","year":2020,"indication":"PET localisation of somatostatin receptor-positive neuroendocrine tumours in adult patients"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus injection","schedule":"148 MBq (4 mCi), imaging approximately 60 minutes after injection","source":"https://www.accessdata.fda.gov/Drugsatfda_Docs/Label/2020/213227s000lbl.Pdf"},"toxicity":[{"event":"Nausea","source":"https://www.accessdata.fda.gov/Drugsatfda_Docs/Label/2020/213227s000lbl.Pdf"},{"event":"Vomiting","source":"https://www.accessdata.fda.gov/Drugsatfda_Docs/Label/2020/213227s000lbl.Pdf"},{"event":"Flushing","source":"https://www.accessdata.fda.gov/Drugsatfda_Docs/Label/2020/213227s000lbl.Pdf"}],"access":[],"regulatoryEvents":[],"route":"/drugs/cu-64-dotatate/"}
{"id":"ga-68-dotatoc","kind":"drug","name":"Gallium-68 edotreotide (DOTATOC)","aka":["68Ga-DOTATOC","Ga 68 DOTATOC Injection","Edotreotide"],"tldr":"A cousin of the Ga-68 DOTATATE and Cu-64 DOTATATE scans: it sticks to the same receptor on neuroendocrine tumours and lets PET find them. It is FDA-approved but, unusually, has no brand name and no pharmaceutical-company sponsor.","summary":"Ga 68 DOTATOC Injection was approved by FDA on 21 August 2019 under NDA 210828, an unusual academic new drug application held by the University of Iowa Health Care PET Imaging Center rather than a company. Approval covered PET localisation of somatostatin receptor-positive neuroendocrine tumours in adult and paediatric patients, based on a retrospective analysis of three prospective trials plus a literature meta-analysis; no deaths or serious adverse events were reported among the 334 patients reviewed for the pivotal readout. In the EU, the equivalent product is licensed as SomaKit TOC (December 2016).\n\nThe adult dose is 148 MBq (4 mCi), with a paediatric weight-based dose of 1.59 MBq/kg (minimum 11.1 MBq, maximum 111 MBq). Because it has no proprietary name, it is often described in the literature simply as 68Ga-DOTATOC. In direct comparisons, 68Ga-DOTATOC and 64Cu-DOTATATE perform similarly, while 18F-FDOPA has shown superior sensitivity for pheochromocytoma specifically. The therapeutic counterpart of the same peptide, 177Lu-edotreotide (ITM-11), remains unapproved in the US as of September 2026 after a complete response letter over manufacturing issues.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA approval letter, NDA 210828, Ga-68-DOTATOC (2019)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210828Orig1s000Approv.pdf"},{"label":"FDA multi-discipline review, NDA 210828","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210828Orig1s000MultidisciplineR.pdf"},{"label":"Sunderland & Graham, J Nucl Med 2020: an academic medical centre's journey through the FDA NDA process for 68Ga-DOTATOC","url":"https://jnm.snmjournals.org/content/jnumed/early/2020/02/06/jnumed.119.238287.full.pdf"}],"tags":["SSTR2","NET imaging","academic NDA"],"related":["cu-64-dotatate","ga68-dotatate","itm-11","f-18","ga-68","cu-64","lu-177"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":["sstr-pet","pet-ct"],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A somatostatin analogue peptide (octreotide backbone with a DOTA chelator) that binds somatostatin receptor subtype 2, the same receptor targeted by DOTATATE. DOTATOC has somewhat higher affinity for SSTR5 than DOTATATE, which can matter for a minority of tumours, but the two peptides are broadly interchangeable in practice.","approvals":[{"region":"US","year":2019,"indication":"PET localisation of somatostatin receptor-positive neuroendocrine tumours in adult and paediatric patients"},{"region":"EU","year":2016,"indication":"PET localisation of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (as SomaKit TOC)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"Adults: 148 MBq (4 mCi), range 111-185 MBq; paediatric: 1.59 MBq/kg, minimum 11.1 MBq, maximum 111 MBq","source":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210828Orig1s000MultidisciplineR.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ga-68-dotatoc/"}
{"id":"in-111-pentetreotide","kind":"drug","name":"Indium-111 pentetreotide","aka":["111In-pentetreotide","OctreoScan"],"tldr":"The original nuclear medicine scan for finding neuroendocrine tumours, used before PET scans like Ga-68 DOTATATE became available. It is still FDA-approved but has largely been superseded because PET gives sharper pictures with less radiation.","summary":"OctreoScan (kit for the preparation of indium In-111 pentetreotide) was approved by FDA in 1994 (NDA 020314) and is still marketed, now by Curium, as a two-vial kit that the radiopharmacy combines before injection. It is indicated for scintigraphic localisation of primary and metastatic neuroendocrine tumours bearing somatostatin receptors, at a recommended dose of 111 MBq (3 mCi) for planar imaging or 222 MBq (6 mCi) for SPECT.\n\nOctreoScan was the standard-of-care functional imaging test for neuroendocrine tumours for roughly two decades, but head-to-head studies have consistently shown that the newer PET tracers (68Ga-DOTATATE, 68Ga-DOTATOC, 64Cu-DOTATATE) detect more lesions with better spatial resolution and lower radiation dose, and most guideline bodies (SNMMI, ENETS) now favour SSTR-PET where it is available. OctreoScan remains relevant where PET access is limited, and it has a long track record: the label carries specific precautions for insulinoma patients, who can develop severe hypoglycaemia with unlabelled octreotide co-administration, and the finished radiopharmaceutical must be used within six hours of preparation.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Octreoscan (kit for the preparation of Indium In 111 Pentetreotide Injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020314Orig1s000Lbl.pdf"}],"tags":["SSTR2","SPECT","legacy agent"],"related":["cu-64-dotatate","ga-68-dotatoc","ga68-dotatate","ga-68","in-111","cu-64"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":["spect","spect-ct"],"targets":["sstr2"],"drugs":[],"companies":["curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"OctreoScan","modality":"SPECT tracer","mechanism":"Pentetreotide is an octreotide derivative conjugated to the chelator DTPA; once labelled with indium-111 it binds somatostatin receptor subtype 2 on neuroendocrine tumour cells. Because indium-111 is a gamma emitter rather than a positron emitter, imaging is by SPECT (or SPECT/CT) rather than PET.","approvals":[{"region":"US","year":1994,"indication":"Scintigraphic localisation of primary and metastatic neuroendocrine tumours bearing somatostatin receptors"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection, after radiolabelling the kit","schedule":"111 MBq (3 mCi) for planar imaging; 222 MBq (6 mCi) for SPECT imaging; use within 6 hours of preparation","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020314Orig1s000Lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/in-111-pentetreotide/"}
{"id":"i-123-mibg","kind":"drug","name":"Iobenguane I-123","aka":["123I-MIBG","AdreView","Iobenguane I 123 Injection"],"tldr":"An injectable tracer that mimics a stress hormone and gets taken up by certain nerve-related tumours, such as pheochromocytoma and childhood neuroblastoma, so a scan afterwards can show where they are.","summary":"AdreView (Iobenguane I 123 Injection) was approved by FDA in 2008 for detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests, and gained a second, unrelated cardiac indication in 2013 (assessment of myocardial sympathetic innervation in heart failure via the heart-to-mediastinum ratio). The adult dose is 10 mCi (370 MBq) IV, and patients require thyroid-blocking medication beforehand to prevent free iodine-123 accumulating in the thyroid.\n\nThe most common adverse reactions in the pivotal trials -- dizziness, rash, pruritus, flushing, headache and injection-site haemorrhage -- occurred in under 1.3% of patients, and the product is contraindicated only in known hypersensitivity to iobenguane or iobenguane sulfate. It contains benzyl alcohol as a preservative, which carries a specific warning against use in premature or low-birth-weight infants (\"gasping syndrome\"). In oncology, 123I-MIBG scintigraphy remains part of SNMMI/EANM guideline workups for pheochromocytoma/paraganglioma and paediatric neuroblastoma, though 18F-FDOPA and 68Ga-DOTATATE PET have overtaken it in sensitivity for many indications, and 131I-MIBG is the therapeutic counterpart used once MIBG uptake is confirmed.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: AdreView (Iobenguane I 123 Injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022290s005lbl.pdf"},{"label":"FDA supplemental approval letter, NDA 22-290 (2013 cardiac indication)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/022290orig1s001ltr.pdf"}],"tags":["MIBG","SPECT","pheochromocytoma","neuroblastoma"],"related":["i131-mibg","iobenguane-i-131","f-18","ga-68","i-123","i-131"],"indications":["pheochromocytoma-paraganglioma","neuroblastoma","metastatic-ppgl"],"sections":[],"technologies":["spect","mibg-theranostics"],"targets":[],"drugs":[],"companies":["ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"AdreView","modality":"SPECT tracer","mechanism":"Iobenguane (meta-iodobenzylguanidine, MIBG) is structurally related to noradrenaline and is taken up by the noradrenaline transporter into sympathetic neurons and neuroendocrine cells derived from the neural crest, including pheochromocytoma, paraganglioma and neuroblastoma cells. Labelling with the gamma emitter iodine-123 allows whole-body gamma-camera or SPECT imaging.","approvals":[{"region":"US","year":2008,"indication":"Detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests"},{"region":"US","year":2013,"indication":"Scintigraphic assessment of myocardial sympathetic innervation in NYHA class II/III heart failure with LVEF <=35% (non-oncology indication)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection over 1-2 minutes","schedule":"10 mCi (370 MBq) for patients >=16 years or <16 years and >=70 kg; weight-scaled dose otherwise; thyroid blockade required beforehand","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022290s005lbl.pdf"},"toxicity":[{"event":"Dizziness, rash, pruritus, flushing, headache or injection-site haemorrhage (combined)","anyGradePct":1.3,"source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022290s005lbl.pdf"}],"access":[],"regulatoryEvents":[],"route":"/drugs/i-123-mibg/"}
{"id":"f-18-fdopa","kind":"drug","name":"Fluorodopa F-18","aka":["18F-FDOPA","6-[18F]fluoro-L-DOPA","Fluorodopa F 18 Injection"],"tldr":"A tracer originally built to look at brain dopamine cells in suspected Parkinson's disease. Because certain hormone-producing tumours use the same chemical machinery, doctors also use it, off-label, to find those tumours -- especially adrenal gland tumours called pheochromocytoma.","summary":"Fluorodopa F 18 Injection was approved by FDA in 2019 (NDA 200655, sponsor The Feinstein Institutes for Medical Research) solely for PET imaging of dopaminergic nerve terminals in adults with suspected Parkinsonian syndromes; that is a neurological indication, not an oncological one, and it is the only indication on the US label. The recommended dose is 185 MBq (5 mCi) IV.\n\nIn oncology, 18F-FDOPA is used off-label, but with strong evidence and explicit guideline support: the 2019 EANM/SNMMI procedure standard for phaeochromocytoma and paraganglioma names 18F-FDOPA (alongside 123I-MIBG) as a first-line tracer, ahead of 68Ga-DOTATATE and 18F-FDG. In a prospective head-to-head study of 97 patients, FDOPA detected all 55 confirmed pheochromocytomas versus 25 of 55 for 68Ga-DOTATOC (sensitivity 100% vs 49%, p<0.0001), though DOTATATE-family tracers retain an edge for extra-adrenal and SDHx-related metastatic disease. FDOPA is also used, again off-label, in brain tumour imaging (glioma grading and recurrence, alongside FET) under joint EANM/EANO/RANO/SNMMI amino-acid PET guidelines.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Fluorodopa F 18 Injection","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/200655s000lbl.pdf"},{"label":"Prospective comparison of 18F-FDOPA and 68Ga-DOTATOC PET/CT in pheochromocytoma/paraganglioma (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10728412/"},{"label":"EANM/SNMMI 2019 practice guideline for radionuclide imaging of phaeochromocytoma and paraganglioma","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2019/EANM%20SNMMI%20guideline%20on%20radionuclide%20imaging%20of%20phaeochromocytoma%20and%20paraganglioma.pdf"}],"tags":["amino acid PET","off-label oncology use","PPGL"],"related":["cu-64-dotatate","ga-68-dotatoc","i-123-mibg","f-18-fet","f-18","ga-68","i-123"],"indications":["pheochromocytoma-paraganglioma","metastatic-ppgl","neuroendocrine","glioblastoma"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A fluorinated analogue of L-DOPA that is taken up by the amino-acid transport system and converted by aromatic L-amino-acid decarboxylase (AADC) into a trapped dopamine analogue. Dopaminergic neurons take it up for the FDA-approved neurological indication; the same AADC pathway is highly active in cells of neural-crest and neuroendocrine origin, which is why the tracer also concentrates strongly in pheochromocytoma, paraganglioma and other well-differentiated neuroendocrine tumours.","approvals":[{"region":"US","year":2019,"indication":"PET imaging to visualise dopaminergic nerve terminals in the striatum in adults with suspected Parkinsonian syndromes (neurological indication; oncology use is off-label)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection over 1 minute","schedule":"185 MBq (5 mCi) in adults","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/200655s000lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-fdopa/"}
{"id":"f-18-fet","kind":"drug","name":"Floretyrosine F-18 (FET)","aka":["18F-FET","O-(2-[18F]fluoroethyl)-L-tyrosine","Pixclara","TLX101-Px"],"tldr":"A brain-tumour PET tracer that shows where active tumour tissue is by how much it grabs a labelled amino acid, which helps tell a true regrowing tumour apart from scan changes caused by past treatment. Approved by the FDA in September 2026, the first scan of its kind cleared for this use in the US.","summary":"Pixclara (floretyrosine F 18, 18F-FET) was approved by FDA on 11 September 2026 (the PDUFA goal date), after an initial complete response letter in April 2025 requesting additional confirmatory clinical evidence and a resubmission by Telix in March 2026. It is indicated for use with PET to differentiate recurrent or progressive glioma from treatment-related change, alongside other diagnostic evaluations, in adults and children from 1 month of age -- making it the first FDA-approved radiopharmaceutical imaging drug for glioma in the US. Safety was assessed in 382 glioma patients; the only adverse reaction at or above 0.5% incidence was headache, with nausea, injection-site reaction, fatigue and malaise each occurring in under 0.5%.\n\nFET-PET has been used in Europe and recommended by joint EANM/EANO/RANO/SNMMI guidelines for glioma imaging for over a decade, well ahead of US approval: recommended adult activity is 185-200 MBq, with a tumour-to-brain SUV ratio threshold of roughly 1.6-1.8 used to define biological tumour volume, and a maximum tumour-to-brain ratio of at least 2.5 associated with a 98% positive predictive value for neoplasm in newly diagnosed lesions. The Pixclara US label sets the adult dose at 185-259 MBq (5-7 mCi) and a paediatric weight-based dose from 1 month of age. The agent remains in a phase 3 registrational study for a possible brain-metastases indication, which is not yet part of the approved US label.","status":"approved","asOf":"2026-09-27","links":[{"label":"Drugs@FDA: NDA 218592, Pixclara (floretyrosine F 18)","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218592"},{"label":"Pixclara (floretyrosine F 18) US Prescribing Information, Telix Pharmaceuticals","url":"https://telixpharma.com/wp-content/uploads/2026/09/USPI_PIXCLARA_Sep2026.pdf"},{"label":"Telix press release: FDA approves Pixclara, 14 September 2026","url":"https://telixpharma.com/news-views/fda-approves-telixs-brain-cancer-imaging-drug-pixclara/"},{"label":"Joint EANM/EANO/RANO/SNMMI practice guidelines for PET imaging of gliomas with radiolabelled amino acids and FDG (2018)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6351513/"}],"tags":["amino acid PET","glioma","newly approved"],"related":["f-18-fdopa","f-18"],"indications":["glioblastoma"],"sections":[],"technologies":["pet","pet-ct"],"targets":[],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Pixclara","modality":"PET tracer","mechanism":"An amino-acid analogue taken up by the L-type amino-acid transporters (LAT1/LAT2) that are upregulated on glioma cells, without being metabolically incorporated into protein. Because uptake tracks amino-acid transport rather than glucose metabolism, it gives much better contrast than FDG in the brain, where normal grey matter is a high glucose consumer but a low amino-acid transporter.","approvals":[{"region":"US","year":2026,"indication":"Use with PET to differentiate recurrent or progressive glioma from treatment-related change, in conjunction with other diagnostic evaluations, in adults and paediatric patients 1 month of age and older"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus injection","schedule":"Adults: 185-259 MBq (5-7 mCi); paediatric patients 1 month and older: 3 MBq/kg (0.081 mCi/kg), minimum 14 MBq, maximum 259 MBq","source":"https://telixpharma.com/wp-content/uploads/2026/09/USPI_PIXCLARA_Sep2026.pdf"},"toxicity":[{"event":"Headache","anyGradePct":0.5,"source":"https://telixpharma.com/wp-content/uploads/2026/09/USPI_PIXCLARA_Sep2026.pdf"}],"access":[],"regulatoryEvents":[{"date":"2026-09-11","type":"approval","region":"US","note":"Pixclara, NDA 218592 (Telix Pharmaceuticals US), original approval; FDA classification Type 1 new molecular entity","source":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218592"}],"route":"/drugs/f-18-fet/"}
{"id":"tc-99m-mdp","kind":"drug","name":"Technetium Tc-99m medronate (MDP)","aka":["99mTc-MDP","Technetium Tc 99m Medronate","CIS-MDP","Draximage MDP-25"],"tldr":"The standard, decades-old bone scan: a radioactive tracer that sticks to areas of bone rebuilding, so a gamma-camera picture afterwards shows where cancer may have spread to bone, or where a fracture or infection is healing.","summary":"Technetium Tc 99m Medronate is supplied as a cold kit -- a vial of medronic acid and stannous chloride that the radiopharmacy reconstitutes with the hospital's own technetium-99m generator eluate -- under several long-approved NDAs (e.g. Draximage MDP-25, NDA 018035; CIS-MDP, NDA 018124). It is indicated broadly as a bone imaging agent to delineate areas of altered osteogenesis, without an oncology-specific label claim, but the single largest clinical use remains detecting osteoblastic skeletal metastases, chiefly from prostate and breast cancer, alongside benign indications such as fracture, infection and metabolic bone disease.\n\nThe recommended adult dose is 370-740 MBq (10-20 mCi) IV, with optimal imaging 1-4 hours later; about half the injected dose is retained in the skeleton and half is excreted in urine within 24 hours. The label carries no listed contraindications but flags allergic dermatological reactions reported with the diphosphonate class, and a 2025 label update added a warning about altered biodistribution in the presence of high levels of certain cations (iron, calcium, aluminium). Despite the rise of 18F-NaF PET and, in prostate cancer, PSMA PET, 99mTc-MDP bone scintigraphy remains the most widely available and lowest-cost skeletal survey worldwide.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Draximage MDP-25 (Kit for the Preparation of Technetium Tc 99m Medronate Injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/018035s043lbl.pdf"},{"label":"FDA label: CIS-MDP (Kit for the Preparation of Technetium Tc 99m Medronate)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018124s013lbl.pdf"}],"tags":["bone scan","SPECT","cold kit","generic"],"related":["f-18-naf","f-18","tc-99m"],"indications":["prostate"],"sections":[],"technologies":["spect","spect-ct","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":["curium","ge-healthcare"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"SPECT tracer","mechanism":"Medronate (methylene diphosphonate) is a bisphosphonate that chelates technetium-99m and, once injected, adsorbs onto the hydroxyapatite crystal surface of bone in proportion to local osteoblastic activity and blood flow -- the same underlying biology as 18F-NaF PET, but imaged with a conventional gamma camera or SPECT rather than PET.","approvals":[{"region":"US","year":1972,"indication":"Bone imaging agent to delineate areas of altered osteogenesis"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection over ~30 seconds, after kit reconstitution","schedule":"370-740 MBq (10-20 mCi) in an average 70 kg adult; optimal imaging 1-4 hours post-injection","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/018035s043lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-mdp/"}
{"id":"cu-64-sar-bispsma","kind":"drug","name":"Copper-64 SAR-bisPSMA","aka":["64Cu-SAR-bisPSMA","64Cu-bisPSMA"],"tldr":"An experimental PET tracer for prostate cancer that binds the same target as approved PSMA scans (PSMA) but, because its radioactive tag lasts longer, can be re-imaged a day later to catch small deposits the first picture missed. It is not yet approved for sale.","summary":"64Cu-SAR-bisPSMA is Clarity Pharmaceuticals' diagnostic partner to its therapeutic 67Cu-SAR-bisPSMA, developed as a Targeted Copper Theranostic pair. In the phase 1 PROPELLER trial (NCT04839367, 30 men with intermediate-to-high-risk untreated prostate cancer), the optimal 200 MBq dose detected primary prostate cancer in 100% and 85.7% of patients by two independent readers, versus 77.8% and 83.3% for same-patient 68Ga-PSMA-11, with significantly higher SUVmax and tumour-to-background ratio (p<0.001 for both readers). In the Co-PSMA trial (NCT06907641, 50 men with biochemical recurrence after prostatectomy), 24-hour 64Cu-SAR-bisPSMA imaging found more than double the per-patient lesion count of same-day 68Ga-PSMA-11 (mean 1.26 vs 0.48 lesions, p<0.0001) and changed management in 44% of patients, published in European Urology in 2026.\n\nThe US FDA granted 64Cu-SAR-bisPSMA fast-track designation in August 2024 for PET imaging of PSMA-positive prostate cancer with suspected metastasis in patients eligible for initial definitive therapy. A registrational phase 3 trial, CLARIFY (NCT06056830), is evaluating same-day and next-day imaging ahead of radical prostatectomy. The therapeutic isotope pairing, 67Cu-SAR-bisPSMA, is being tested in the SECuRE trial (NCT04868604) for PSMA-expressing metastatic castration-resistant prostate cancer; both 64Cu- and 67Cu-SAR-bisPSMA remain unregistered products not yet assessed for approval by FDA or Australia's TGA, per the company's own disclosures.","status":"phase-3","asOf":"2026-09-22","links":[{"label":"Lengyelova, Wong, Lenzo, Parker, Emmett; JCO 2023: 64Cu-SAR-bisPSMA (PROPELLER) PET imaging in confirmed prostate cancer","url":"https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5039"},{"label":"Co-PSMA trial, European Urology 2026: prospective comparison of 64Cu-SAR-bisPSMA vs 68Ga-PSMA-11 for biochemical recurrence","url":"https://pubmed.ncbi.nlm.nih.gov/41904043/"},{"label":"ClinicalTrials.gov NCT04868604 (SECuRE)","url":"https://clinicaltrials.gov/study/NCT04868604"}],"tags":["PSMA","copper-64","theranostic pair","investigational"],"related":["tc-99m-psma-imaging","ga-68","cu-64","cu-67"],"indications":["prostate-high-risk","prostate-bcr","prostate-mcrpc"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":["psma"],"drugs":[],"companies":["clarity-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04868604"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A bivalent small-molecule ligand carrying two PSMA-binding moieties on a single sarcophagine (SAR) chelator backbone, labelled with copper-64. The bivalent design and copper-64's 12.7-hour half-life allow same-day and next-day imaging from a single injection, and Clarity Pharmaceuticals reports two- to three-fold higher tumour uptake (SUVmax) than the standard-of-care 68Ga-PSMA-11 in head-to-head comparisons.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/cu-64-sar-bispsma/"}
{"id":"tc-99m-psma-imaging","kind":"drug","name":"Technetium Tc-99m PSMA agents (PSMA-I&S)","aka":["99mTc-PSMA-I&S","Tc-99m PSMA imaging and surgery"],"tldr":"A version of the PSMA prostate cancer scan that uses the same cheap, widely available radioactive tag as a standard bone scan instead of the PET tracers. Surgeons can also carry a small radiation detector into the operating room to help find and remove cancerous lymph nodes. It has not been through formal drug approval; it is used as an academic, in-house preparation.","summary":"99mTc-PSMA-I&S ([99mTc]Tc-mas3-y-nal-k(Sub-KuE)) was developed at the Technical University of Munich as a cost-effective, kit-based alternative to 111In-PSMA-I&T for PSMA-targeted radioguided surgery, first reported in the Journal of Nuclear Medicine in 2017. In that first-in-human report, preoperative SPECT/CT at 12 hours after injection showed high uptake in all lesions previously identified by 68Ga-PSMA-11 PET/MR, and a handheld gamma probe successfully guided intraoperative resection of metastatic lymph nodes down to 3 mm.\n\nBeyond radioguided surgery, retrospective single-centre series have used PSMA-I&S SPECT/CT as a stand-alone diagnostic tool: one series reported patient-based sensitivity, specificity and accuracy of 86%, 100% and 92% for detecting primary prostate cancer, and for restaging in biochemical recurrence, sensitivity of 67% with specificity of 100%, generally trailing PSMA-PET's reported sensitivity in the low-PSA setting but offering same-day, low-cost imaging with equipment most nuclear medicine departments already own. Because it is produced from an academic cold-kit under local institutional protocols rather than an FDA- or EMA-reviewed marketing application, it has no formal regulatory approval or labelled dose; reported clinical activities have ranged from roughly 500-700 MBq for combined SPECT-and-surgery protocols.","status":"emerging","asOf":"2026-09-22","links":[{"label":"Robu et al., J Nucl Med 2017: preclinical evaluation and first patient application of 99mTc-PSMA-I&S for SPECT imaging and radioguided surgery in prostate cancer","url":"https://jnm.snmjournals.org/content/58/2/235.full.pdf"},{"label":"Diagnostic value of 99mTc-PSMA-I&S SPECT/CT for prostate cancer detection and staging (2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10798073/"}],"tags":["PSMA","SPECT","radioguided surgery","academic cold kit"],"related":["cu-64-sar-bispsma","in-111-pentetreotide","ga-68","tc-99m","in-111"],"indications":["prostate","prostate-bcr"],"sections":[],"technologies":["spect","spect-ct"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"SPECT tracer","mechanism":"PSMA-I&S (\"imaging and surgery\") is a urea-based small-molecule PSMA inhibitor labelled with technetium-99m via a MAS3 chelator. It binds prostate-specific membrane antigen on prostate cancer cells; because technetium-99m is a gamma emitter available from any hospital's own generator (unlike gallium-68 or fluorine-18, which need a generator or cyclotron dedicated to PET production), it can be used both for pre-operative SPECT/CT localisation and, with a handheld gamma probe, for intraoperative radioguided surgery.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-psma-imaging/"}
{"id":"f-18-fluorothymidine","kind":"drug","name":"Fluorothymidine F-18 (FLT)","aka":["18F-FLT","3'-deoxy-3'-[18F]fluorothymidine"],"tldr":"An experimental PET tracer that measures how fast tumour cells are dividing, rather than how much sugar they burn. It has been studied in research settings for over 20 years but has never been approved as a medicine.","summary":"18F-FLT has been an investigational PET agent since it was first reported in 1998, and remains one so today: it is supplied only under Investigational New Drug (IND) exemptions or Radioactive Drug Research Committee (RDRC)-approved basic science protocols, and no marketing application has been filed anywhere. The US National Cancer Institute's Cancer Imaging Program holds a centralised, multi-source IND that lets academic sites use FLT made by any of several suppliers with a Drug Master File on record, which has supported dozens of single- and multi-centre trials, mostly in breast, lung and brain cancer, evaluating early response to chemotherapy.\n\nFLT's main limitation is that its signal is diluted by TK1 activity in normal proliferating tissue -- bone marrow and liver in particular -- giving high background uptake that can obscure metastases in those organs, and its plasma level is affected by co-administered chemotherapy and some pain medications via hepatic glucuronidation. Studies correlate FLT uptake with the Ki-67 proliferation marker in breast, lung and brain tumours, and FLT-PET has shown early, quantifiable drops in uptake after starting chemotherapy, but larger controlled trials with survival endpoints have not been completed, and no clinical guideline currently recommends it outside a trial setting.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"NCI Investigator's Brochure: [F-18]FLT, an investigational PET radiopharmaceutical","url":"https://dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/flt-ib.pdf"},{"label":"Applications of PET imaging with the proliferation marker 18F-FLT (review, 2015)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4415691/"},{"label":"SNMMI PET Center of Excellence FLT factsheet","url":"https://snmmi.org/common/Uploaded%20files/Web/Centers/PET%20Center%20of%20Excellence/FLT_07-11-12%20Final.pdf"}],"tags":["proliferation imaging","investigational","TK1"],"related":["f-18"],"indications":["breast-her2-positive","glioblastoma","nsclc"],"sections":[],"technologies":["pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A thymidine analogue that is taken up and phosphorylated by thymidine kinase 1 (TK1) during the S-phase of the cell cycle, then trapped intracellularly because the phosphorylated form cannot cross the cell membrane back out. Because TK1 activity tracks DNA synthesis, FLT uptake is a direct measure of cellular proliferation rather than glucose metabolism (which 18F-FDG measures) -- in principle a closer PET analogue of the Ki-67 proliferation index measured on biopsy.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-fluorothymidine/"}
{"id":"ga-67-citrate","kind":"drug","name":"Gallium citrate Ga-67","aka":["67Ga-citrate","Gallium Citrate Ga 67"],"tldr":"One of the oldest cancer-imaging scans still on the market: an injectable form of radioactive gallium that collects in lymphomas and some other tumours (and in infections), imaged one to five days later. It has mostly been replaced by FDG-PET but is still FDA-approved and occasionally used.","summary":"Gallium Citrate Ga 67 Injection has held FDA approval since the 1970s (NDA 017478) for demonstrating the presence and extent of Hodgkin's disease, other lymphomas and bronchogenic carcinoma, and as an aid in detecting some acute inflammatory lesions; it is currently labelled and marketed by Curium. The adult dose is 74-185 MBq (2-5 mCi) IV, with optimal images typically obtained 48 hours post-injection, though acceptable images can be acquired anywhere from 6 to 120 hours afterward given considerable inter-patient biological variability.\n\nThe label itself flags the tracer's major limitation: up to 40% false-negative rates in some pathological conditions, an inability to distinguish tumour from acute inflammation without additional studies, and poor performance in lymphocytic lymphoma specifically, which the label states is not recommended for gallium imaging. FDG-PET has substantially displaced Ga-67 citrate for lymphoma staging and for fever-of-unknown-origin workups because it offers same-day imaging, higher spatial resolution and better sensitivity; gallium scintigraphy's most durable remaining niche is spinal and musculoskeletal infection imaging (often as SPECT/CT) in settings where FDG-PET is unavailable.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Gallium Citrate Ga-67 Injection (DailyMed, Curium US LLC)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f670c12-cca5-4d73-8a88-241f753d1bc7"}],"tags":["legacy agent","lymphoma imaging","SPECT"],"related":["ga-67"],"indications":[],"sections":[],"technologies":["spect","spect-ct"],"targets":[],"drugs":[],"companies":["curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"SPECT tracer","mechanism":"Free gallium ion, delivered as the citrate salt, is thought to accumulate in lysosomes and bind a soluble intracellular protein in certain viable tumours and in focal sites of infection or inflammation; the exact mechanism has never been fully characterised despite the tracer's decades of clinical use. Gallium-67 decays by electron capture with several gamma photopeaks, requiring a medium-energy collimator and triple-energy-window acquisition.","approvals":[{"region":"US","year":1976,"indication":"Demonstrating the presence and extent of Hodgkin's disease, lymphoma and bronchogenic carcinoma; aid in detecting some acute inflammatory lesions"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"74-185 MBq (2-5 mCi) in an average 70 kg adult; optimal imaging around 48 hours post-injection, acceptable from 6-120 hours","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f670c12-cca5-4d73-8a88-241f753d1bc7"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ga-67-citrate/"}
{"id":"alzheimers-disease","kind":"indication","name":"Alzheimer's disease","aka":[],"tldr":"The most common cause of dementia, in which sticky amyloid protein and tangled tau protein build up in the brain and damage memory and thinking over years.","summary":"Alzheimer's disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Pathologically it is defined by extracellular amyloid-beta neuritic plaques and intracellular tau neurofibrillary tangles, which typically precede clinical symptoms by a decade or more. Clinical diagnosis on history and neuropsychological testing alone is imprecise, particularly in atypical or early presentations, so tissue-level confirmation of amyloid and, increasingly, tau pathology has become part of routine specialist work-up.\n\nAmyloid PET tracers (florbetapir, flutemetamol, florbetaben) and the tau tracer flortaucipir let clinicians see this pathology in a living patient. A negative amyloid scan is strong evidence against AD as the cause of cognitive impairment; a positive scan is consistent with AD but is not diagnostic on its own, since amyloid deposition also occurs in a minority of cognitively normal older adults. The 2024 Alzheimer's Association revised criteria treat a positive amyloid biomarker (PET or CSF) as a 'Core 1' biomarker sufficient, together with clinical context, to support a biological diagnosis of AD, with tau PET as a 'Core 2' biomarker used to stage disease severity.\n\nFrom 2023 onward the field entered a treatment era: the anti-amyloid monoclonal antibodies lecanemab (Leqembi) and donanemab (Kisunla) received full FDA approval for early symptomatic AD (mild cognitive impairment or mild dementia), and both require documented amyloid pathology, established by PET or CSF, before starting therapy. This has turned amyloid PET from a largely diagnostic-exclusion tool into a gatekeeping test for a treatable population, and serial quantitative amyloid PET (reported in Centiloids) is used by some centres to decide when plaque clearance is sufficient to stop donanemab dosing.","asOf":"2026-09-22","links":[{"label":"SNMMI/Alzheimer's Association: updated appropriate use criteria for amyloid and tau PET (2025)","url":"https://jnm.snmjournals.org/content/early/2025/01/07/jnumed.124.268756"},{"label":"FDA: Amyvid label update supporting amyloid-targeting therapy selection (June 2025)","url":"https://investor.lilly.com/news-releases/news-release-details/fda-approves-updated-label-lillys-amyvid-florbetapir-f-18"}],"tags":["neurology","dementia"],"related":["f-18-florbetapir","f-18-flutemetamol","f-18-florbetaben","f-18-flortaucipir","f-18-fdg-brain"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"neurology","subtypes":[],"biomarkers":[],"standardOfCare":[],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"route":"/indications/alzheimers-disease/"}
{"id":"parkinsonian-syndromes","kind":"indication","name":"Parkinsonian syndromes","aka":[],"tldr":"A group of movement disorders, including Parkinson's disease, that cause tremor, stiffness and slow movement because the brain loses nerve cells that make dopamine.","summary":"Parkinsonian syndromes include idiopathic Parkinson's disease and the atypical parkinsonisms multiple system atrophy and progressive supranuclear palsy. All share loss of dopaminergic nerve terminals in the striatum, which produces the clinical triad of tremor, rigidity and bradykinesia. A common diagnostic problem is distinguishing these conditions, in their early stages, from essential tremor and other tremor syndromes that do not involve dopaminergic degeneration and are managed quite differently.\n\nDopamine transporter (DAT) SPECT imaging with ioflupane I-123 visualises the density of presynaptic dopamine transporters in the striatum. A normal scan argues strongly against a parkinsonian syndrome and points to essential tremor or a non-degenerative cause; an abnormal scan (reduced or absent striatal uptake) supports a diagnosis of a parkinsonian syndrome but, as the drug label makes explicit, cannot distinguish Parkinson's disease from multiple system atrophy or progressive supranuclear palsy, which all produce similar transporter loss. The same tracer is also used to separate dementia with Lewy bodies, which has striatal dopaminergic loss, from Alzheimer's disease, which does not.\n\nDAT SPECT does not have an equivalent role to amyloid PET in gatekeeping a disease-modifying drug: there is no approved therapy that requires a positive DAT scan before treatment. Its clinical value is diagnostic clarification early in the disease course, when clinical signs are ambiguous and management (dopaminergic therapy vs none) hinges on getting the category right.","asOf":"2026-09-22","links":[{"label":"EMA EPAR: DaTSCAN (ioflupane (123I))","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/datscan"},{"label":"FDA label: DaTscan (ioflupane I 123 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022454s010lbl.pdf"}],"tags":["neurology","movement disorder"],"related":["i-123-ioflupane","i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"neurology","subtypes":[],"biomarkers":[],"standardOfCare":[],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"route":"/indications/parkinsonian-syndromes/"}
{"id":"f-18-florbetapir","kind":"drug","name":"Florbetapir F-18","aka":["Amyvid","18F-AV-45"],"tldr":"A PET scan tracer that shows whether a patient's brain contains the sticky amyloid protein clumps linked to Alzheimer's disease, and whether they qualify for amyloid-lowering drugs.","summary":"Florbetapir F-18 (Amyvid, Eli Lilly) was the first amyloid PET tracer approved by the FDA, in April 2012, for imaging beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease (AD) and other causes of cognitive decline. In June 2025 the FDA approved a label update adding a second indication: selection of patients who are candidates for amyloid-beta-directed therapy, reflecting the arrival of approved anti-amyloid antibodies. A negative scan indicates sparse to no neuritic plaques and reduces the likelihood that AD explains the impairment; a positive scan indicates moderate to frequent plaques, a pattern also seen in some cognitively normal older adults, so it does not by itself establish an AD diagnosis and is meant to be used alongside full clinical evaluation.\n\nThe recommended dose is 370 MBq (10 mCi) as a single intravenous bolus in up to 10 mL, followed by a saline flush, with 10-minute PET images acquired approximately 30 to 50 minutes after injection. The maximum mass dose is 50 micrograms. Effective dose from a 370 MBq administration is about 7 mSv in an adult. Reading is by visual assessment of cortical grey-white contrast loss by a trained reader; quantification against the Centiloid scale can be used alongside the visual read, per the 2025 label update, and is the metric used to track amyloid clearance during anti-amyloid antibody therapy.\n\nIn the clinical pathway defined by the 2025 SNMMI/Alzheimer's Association appropriate use criteria, amyloid PET is rated 'appropriate' both for diagnostic clarification in patients with an uncertain aetiology after specialist assessment and, with the highest confidence rating, for determining eligibility for an approved amyloid-targeting therapy such as lecanemab or donanemab. In the United States, Medicare coverage of amyloid PET is no longer restricted: CMS retired the national coverage determination at 42 CFR 220.6.20 effective 13 October 2023, ending the prior coverage-with-evidence-development framework and the one-scan-per-lifetime limit, and coverage decisions (including for repeat scans to document plaque clearance) now sit with local Medicare Administrative Contractors rather than a single national rule.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Amyvid (florbetapir F 18 injection), 2025 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/202008s046lbl.pdf"},{"label":"Eli Lilly: FDA approves updated Amyvid label for treatment selection (25 June 2025)","url":"https://investor.lilly.com/news-releases/news-release-details/fda-approves-updated-label-lillys-amyvid-florbetapir-f-18"},{"label":"CMS: decision memo removing the amyloid PET national coverage determination (NCA-CAL 308)","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=308"},{"label":"SNMMI/Alzheimer's Association: updated appropriate use criteria for amyloid and tau PET (2025)","url":"https://jnm.snmjournals.org/content/early/2025/01/07/jnumed.124.268756"}],"tags":["amyloid PET","diagnostic","neurology"],"related":["alzheimers-disease","f-18-flutemetamol","f-18-florbetaben","f-18-flortaucipir","eli-lilly","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Amyvid","modality":"PET tracer","mechanism":"A fluorine-18 labelled stilbene derivative that binds to fibrillar amyloid-beta neuritic plaques in the brain; the F-18 positron signal is detected by PET, giving a picture of cortical amyloid burden rather than blood flow or metabolism.","approvals":[{"region":"US","year":2012,"indication":"PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for AD and other causes of cognitive decline"},{"region":"US","year":2025,"indication":"Label update adding selection of patients indicated for amyloid beta-directed therapy"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus","schedule":"370 MBq (10 mCi) single dose in up to 10 mL, followed by ~10 mL saline flush; PET imaging 30-50 minutes after injection","monitoring":"Visual read of cortical uptake pattern by a trained reader; quantitative Centiloid analysis may be used alongside the visual read","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/202008s046lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-florbetapir/"}
{"id":"f-18-flutemetamol","kind":"drug","name":"Flutemetamol F-18","aka":["Vizamyl"],"tldr":"A PET scan tracer used to check whether a patient's brain has amyloid plaques, the hallmark of Alzheimer's disease, and whether they can be treated with amyloid-lowering drugs.","summary":"Flutemetamol F-18 (Vizamyl, GE HealthCare) was FDA-approved in October 2013 for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for AD and other causes of cognitive decline. As with the other amyloid tracers, the US label was updated (current version dated 2025/2026) to add a second indication, selection of patients indicated for amyloid beta-directed therapy, alongside the diagnostic indication. The EMA-approved indication (EPAR, EU) is imaging to help diagnose Alzheimer's disease and other causes of memory loss.\n\nThe recommended dose is 185 MBq (5 mCi) given as an intravenous bolus over 40 seconds in up to 10 mL, maximum mass dose 20 micrograms, with 10 to 20-minute PET images acquired 60 to 120 minutes after injection; the resulting effective dose is about 5.9 mSv (32 microSv/MBq). Vizamyl is contraindicated in patients with known hypersensitivity to polysorbate 80, an excipient, which is a distinguishing safety point versus the other amyloid tracers.\n\nInterpretation is by visual assessment of grey-white matter contrast (a positive scan shows loss of the normal grey-white distinction from cortical tracer retention), and flutemetamol has a validated tracer-specific linear conversion to the Centiloid scale, allowing quantitative reporting alongside the qualitative read. In the US, amyloid PET coverage for Medicare beneficiaries, including flutemetamol scans, follows the post-2023 framework in which CMS retired the national coverage determination and left individual coverage decisions to local Medicare Administrative Contractors, removing the former one-scan-per-lifetime limit.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Vizamyl (flutemetamol F 18 injection)","url":"https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=b3558f16-8f9a-4e55-8d9c-836427ebaa57&type=pdf"},{"label":"EMA EPAR product information: Vizamyl","url":"https://www.ema.europa.eu/en/documents/product-information/vizamyl-epar-product-information_en.pdf"},{"label":"Zhang et al.: Centiloid scaling for quantification of brain amyloid with [18F]flutemetamol","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6281542/"},{"label":"CMS: decision memo removing the amyloid PET national coverage determination (NCA-CAL 308)","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=308"}],"tags":["amyloid PET","diagnostic","neurology"],"related":["alzheimers-disease","f-18-florbetapir","f-18-florbetaben","ge-healthcare","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Vizamyl","modality":"PET tracer","mechanism":"A fluorine-18 labelled benzothiazole derivative, structurally related to Pittsburgh Compound-B, that binds fibrillar beta-amyloid plaques for PET detection of cortical amyloid burden.","approvals":[{"region":"US","year":2013,"indication":"PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for AD and other causes of cognitive decline"},{"region":"US","year":2025,"indication":"Label update adding selection of patients indicated for amyloid beta-directed therapy"},{"region":"EU","year":2014,"indication":"Diagnostic use to help diagnose Alzheimer's disease and other causes of memory loss"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus","schedule":"185 MBq (5 mCi) single dose within 40 seconds, in up to 10 mL, flushed with 5-15 mL saline; PET imaging 60-120 minutes after injection","monitoring":"Visual read of cortical grey-white contrast; Centiloid quantification available as an adjunct using a validated tracer-specific conversion equation","source":"https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=b3558f16-8f9a-4e55-8d9c-836427ebaa57&type=pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-flutemetamol/"}
{"id":"f-18-florbetaben","kind":"drug","name":"Florbetaben F-18","aka":["Neuraceq"],"tldr":"A PET scan tracer that lights up amyloid plaques in the brain, helping doctors work out whether memory problems are due to Alzheimer's disease and whether the patient can have amyloid-lowering treatment.","summary":"Florbetaben F-18 (Neuraceq, originally Piramal, now Life Molecular Imaging/Lantheus) was FDA-approved in March 2014 and EMA-approved in February 2014, for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for AD and other causes of cognitive decline. As with florbetapir and flutemetamol, the current US label has been updated to add selection of patients for amyloid beta-directed therapy as a second indication.\n\nThe recommended dose is 300 MBq (8.1 mCi) given as a slow intravenous bolus (6 seconds/mL) in up to 10 mL, maximum mass dose 30 micrograms; PET imaging in the US label starts 45 to 130 minutes post-injection (commonly around 90 minutes), and the EU posology allows 240-360 MBq with the target at 300 MBq. Effective dose from a 300 MBq administration is about 5.8 mSv.\n\nVisual interpretation looks for loss of the normal grey-white matter contrast from increased cortical tracer retention; florbetaben has its own validated linear conversion to the Centiloid scale, and the 2024 EMA/CHMP qualification opinion on the Centiloid measure discusses florbetaben-specific data showing that values above about 35 CL indicate established amyloid pathology while values below about 20 CL are compatible with a negative visual read, with 20-35 CL an ambiguous zone. Neuraceq sits in the same US clinical-use and Medicare-coverage landscape as the other amyloid tracers: appropriate for diagnostic work-up in uncertain cognitive impairment and for confirming eligibility for anti-amyloid antibody therapy per the 2025 SNMMI/Alzheimer's Association appropriate use criteria, with Medicare coverage now determined locally following the October 2023 retirement of the national coverage determination.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Neuraceq (florbetaben F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/204677s041lbl.pdf"},{"label":"EMA EPAR: Neuraceq","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/neuraceq"},{"label":"EMA CHMP: qualification opinion for Centiloid measure of amyloid PET (25 June 2024)","url":"https://www.ema.europa.eu/system/files/documents/other/qualification-opinion-centiloid-measure-amyloid-pet-quantify-brain-amyloid-deposition-en.pdf"},{"label":"CMS: decision memo removing the amyloid PET national coverage determination (NCA-CAL 308)","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=308"}],"tags":["amyloid PET","diagnostic","neurology"],"related":["alzheimers-disease","f-18-florbetapir","f-18-flutemetamol","lantheus","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Neuraceq","modality":"PET tracer","mechanism":"A fluorine-18 labelled stilbene derivative that binds fibrillar beta-amyloid plaques in cortical grey matter, giving a PET signal proportional to plaque density.","approvals":[{"region":"US","year":2014,"indication":"PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for AD and other causes of cognitive decline"},{"region":"EU","year":2014,"indication":"PET imaging of beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease and other causes of cognitive impairment"}],"mechanismSteps":[],"dosing":{"route":"Intravenous slow bolus (6 sec/mL)","schedule":"300 MBq (8.1 mCi) single dose in up to 10 mL; PET imaging roughly 45-130 minutes after injection (US label)","monitoring":"Visual read of cortical grey-white contrast; tracer-specific Centiloid conversion available for quantification","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/204677s041lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-florbetaben/"}
{"id":"f-18-flortaucipir","kind":"drug","name":"Flortaucipir F-18","aka":["Tauvid","18F-AV-1451","18F-T807"],"tldr":"A PET scan tracer that shows the tangled tau protein build-up in the brain seen in Alzheimer's disease, used alongside amyloid testing and clinical assessment, not on its own.","summary":"Flortaucipir F-18 (Tauvid, Eli Lilly, developed by Avid Radiopharmaceuticals) was approved by the FDA on 28 May 2020, the first tau PET tracer to reach the US market. It is indicated for PET imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles in adult patients with cognitive impairment being evaluated for AD; the label explicitly states Tauvid is not indicated for evaluating chronic traumatic encephalopathy, since tau conformation and distribution differ in that condition. The EMA-approved indication (Tauvid EPAR) is PET imaging to assess the neocortical distribution of aggregated tau neurofibrillary tangles.\n\nThe recommended dose is 370 MBq (10 mCi) as an intravenous bolus in up to 10 mL, with a 20-minute PET image acquired starting about 80 minutes post-injection; the maximum mass dose is 20 micrograms and effective dose from 370 MBq is about 8.7 mSv. A positive scan (Braak-stage-like scoring, described in the label as 'B3' tau pathology, meaning widely distributed neocortical uptake in posterolateral temporal, occipital or parietal/precuneus regions with or without frontal involvement) supports a diagnosis of AD only in conjunction with clinical and other diagnostic evaluation; the EMA label also notes variable specificity and the possibility of false positives.\n\nIn the 2024 Alzheimer's Association revised diagnostic criteria, tau PET is treated as a 'Core 2' biomarker used to stage AD severity once amyloid positivity (Core 1) has established the diagnosis, rather than as a stand-alone diagnostic test. The 2025 SNMMI/Alzheimer's Association appropriate use criteria rate tau PET as 'appropriate' (score 8) alongside amyloid PET for determining eligibility for an approved amyloid-targeting therapy, though the workgroup notes that tau PET for treatment eligibility is not itself required in the FDA prescribing information for lecanemab or donanemab. There is no dedicated Medicare national coverage determination for tau PET; it falls under the same PET framework applied by CMS and local Medicare Administrative Contractors as other diagnostic radiopharmaceuticals.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Tauvid (flortaucipir F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212123s031lbl.pdf"},{"label":"EMA EPAR product information: Tauvid","url":"https://www.ema.europa.eu/en/documents/product-information/tauvid-epar-product-information_en.pdf"},{"label":"SNMMI/Alzheimer's Association: updated appropriate use criteria for amyloid and tau PET (2025)","url":"https://jnm.snmjournals.org/content/early/2025/01/07/jnumed.124.268756"},{"label":"PMC review: Tauvid, the first FDA-approved PET tracer for imaging tau pathology","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7911942/"}],"tags":["tau PET","diagnostic","neurology"],"related":["alzheimers-disease","f-18-florbetapir","f-18-flutemetamol","f-18-florbetaben","eli-lilly","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Tauvid","modality":"PET tracer","mechanism":"A fluorine-18 labelled tracer that binds paired helical filament tau, the aggregated, phosphorylated form of tau protein found in neurofibrillary tangles, allowing PET visualisation of the density and spatial spread of tau pathology.","approvals":[{"region":"US","year":2020,"indication":"PET imaging of the brain to estimate density and distribution of aggregated tau neurofibrillary tangles in adults with cognitive impairment being evaluated for Alzheimer's disease"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus","schedule":"370 MBq (10 mCi) single dose in up to 10 mL; 20-minute PET image starting approximately 80 minutes after injection","monitoring":"Visual scoring of neocortical tau pattern distribution (B1-B3 Braak-like staging); used alongside amyloid PET/CSF as a Core 2 staging biomarker","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212123s031lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-flortaucipir/"}
{"id":"f-18-florquinitau","kind":"drug","name":"Florquinitau F-18","aka":["Tauklarify","florquinitau F 18 injection"],"tldr":"A new PET scan tracer, approved by the FDA in August 2026, that shows tangled tau protein in the brain of adults with memory or thinking problems who are being assessed for Alzheimer's disease. It is read alongside other tests: a negative scan does not rule tau out and a positive one does not prove it.","summary":"Tauklarify (florquinitau F 18 injection), sponsored by Cerveau (Lantheus), was approved by the FDA on 13 August 2026 under NDA 220496 (original approval, FDA classification Type 1 new molecular entity, standard review). It is indicated for PET of the brain in adults with cognitive impairment who are being evaluated for Alzheimer's disease, to identify patients with tau neurofibrillary tangle (NFT) pathology. The label limits use to Alzheimer's disease: safety and effectiveness are not established for non-Alzheimer tauopathies, and it warns that a negative scan does not exclude, and a positive scan does not confirm, tau NFT pathology.\n\nThe recommended activity is 185 MBq (5 mCi) as an intravenous bolus in up to 10 mL, with imaging started about 90 minutes after injection; the whole-body effective dose from 185 MBq in an adult is estimated at 5.4 mSv, before any CT. CYP1A2 inducers, including tobacco smoking, should be avoided for at least 7 days beforehand. Effectiveness rests on two blinded read studies (279 and 338 subjects) in which five independent readers per study classified scans as tau-positive or negative against a reference standard built from cognitive status and amyloid PET; in Study 1, positive percent agreement ranged from 80% to 88% across readers and negative percent agreement from 98% to 99%. Across 1,734 subjects in the clinical trials, the most common adverse reaction was headache (0.7%).","status":"approved","asOf":"2026-09-27","links":[{"label":"FDA label: Tauklarify (florquinitau F 18 injection), August 2026","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220496Orig1s000lbl.pdf"},{"label":"Drugs@FDA: NDA 220496, Tauklarify","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220496"},{"label":"FDA approval letter: NDA 220496, 13 August 2026","url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220496Orig1s000ltr.pdf"}],"tags":["tau PET","diagnostic","neurology","newly approved"],"related":["alzheimers-disease","f-18-flortaucipir","f-18-florbetapir","f-18-flutemetamol","f-18-florbetaben","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Tauklarify","modality":"PET tracer","mechanism":"A fluorine-18 labelled tracer that binds aggregated tau protein (in-vitro dissociation constant 0.3 nM in post-mortem brain homogenates containing tau neurofibrillary tangles). It crosses the blood-brain barrier, so PET shows where tau tangles, one of the two lesions that define Alzheimer's disease pathologically, have built up.","approvals":[{"region":"US","year":2026,"indication":"PET of the brain in adults with cognitive impairment who are being evaluated for Alzheimer's disease, to identify patients with tau neurofibrillary tangle pathology"}],"mechanismSteps":[],"dosing":{"route":"Intravenous bolus","schedule":"185 MBq (5 mCi) in up to 10 mL; PET imaging starts approximately 90 minutes after injection","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220496Orig1s000lbl.pdf"},"toxicity":[{"event":"Headache","anyGradePct":0.7,"source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220496Orig1s000lbl.pdf"}],"access":[],"regulatoryEvents":[{"date":"2026-08-13","type":"approval","region":"US","note":"Tauklarify, NDA 220496 (Cerveau/Lantheus), original approval; FDA classification Type 1 new molecular entity, standard review","source":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220496"}],"route":"/drugs/f-18-florquinitau/"}
{"id":"i-123-ioflupane","kind":"drug","name":"Ioflupane I-123","aka":["DaTscan","DaTSCAN","123I-FP-CIT"],"tldr":"A brain scan that shows how many dopamine-releasing nerve endings remain in a part of the brain called the striatum, helping tell shaking from Parkinson's-type disease apart from other kinds of tremor and from Alzheimer's-type memory loss.","summary":"Ioflupane I-123 (DaTscan in the US, DaTSCAN in the EU; GE Healthcare) was approved by the FDA in January 2011 and by the EMA in 2000. It is a SPECT radiopharmaceutical indicated as an adjunct to other diagnostic evaluations for striatal dopamine transporter visualisation in adult patients with suspected Parkinsonian syndromes, to help differentiate essential tremor from tremor due to Parkinson's disease, multiple system atrophy or progressive supranuclear palsy (the scan cannot distinguish between these three), and in adult patients to help differentiate probable dementia with Lewy bodies from Alzheimer's disease (it also cannot separate dementia with Lewy bodies from Parkinson's disease dementia).\n\nThe recommended dose is 111-185 MBq (3-5 mCi) given as a slow intravenous injection over at least 15-20 seconds; a thyroid-blocking agent (potassium iodide solution, Lugol's solution or potassium perchlorate) must be given at least one hour beforehand to limit thyroid uptake of free iodine-123. SPECT imaging is performed 3 to 6 hours after injection. Effective dose is about 3.9-4.6 mSv from a 185 MBq administration, depending on the dosimetry source.\n\nInterpretation is by visual (and increasingly semi-quantitative, using striatal binding ratios against normative databases) assessment of striatal uptake shape and intensity: a normal, symmetric comma- or crescent-shaped pattern argues against a parkinsonian syndrome, while reduced, asymmetric or absent putamen uptake supports one. Unlike amyloid PET, DAT SPECT does not currently gate access to any approved disease-modifying therapy; its clinical role remains diagnostic clarification, particularly in early or atypical presentations where tremor aetiology or the AD-versus-Lewy-body-dementia distinction is unclear on clinical grounds alone.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: DaTscan (ioflupane I 123 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022454s010lbl.pdf"},{"label":"EMA EPAR product information: DaTSCAN","url":"https://www.ema.europa.eu/en/documents/product-information/datscan-epar-product-information_en.pdf"},{"label":"EMA EPAR summary: DaTSCAN","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/datscan"}],"tags":["SPECT","diagnostic","neurology","movement disorder"],"related":["parkinsonian-syndromes","alzheimers-disease","ge-healthcare","i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"DaTscan","modality":"SPECT tracer","mechanism":"An iodine-123 labelled cocaine analogue (N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) that binds presynaptic dopamine transporters on striatal nerve terminals, allowing SPECT visualisation of dopaminergic neuron density.","approvals":[{"region":"US","year":2011,"indication":"Striatal dopamine transporter SPECT imaging as an adjunct in adults with suspected Parkinsonian syndromes, to help differentiate essential tremor from tremor due to Parkinsonian syndromes"},{"region":"EU","year":2000,"indication":"Detecting loss of functional dopaminergic neuron terminals in the striatum in clinically uncertain Parkinsonian syndromes, and to help differentiate probable dementia with Lewy bodies from Alzheimer's disease"}],"mechanismSteps":[],"dosing":{"route":"Slow intravenous injection (>=15-20 seconds)","schedule":"111-185 MBq (3-5 mCi) single dose; thyroid blockade at least 1 hour before injection; SPECT imaging 3-6 hours after injection","monitoring":"Visual assessment of striatal uptake pattern, often supported by semi-quantitative striatal binding ratio software against normative reference data","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022454s010lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/i-123-ioflupane/"}
{"id":"tc-99m-hmpao-brain","kind":"drug","name":"Technetium-99m exametazime (brain perfusion)","aka":["Ceretec","Tc-99m HMPAO","HMPAO"],"tldr":"A cold-kit radioactive tracer that maps blood flow inside the brain on a SPECT scan, used mainly to look for the effects of stroke and, off-label in practice, to help support a diagnosis of brain death.","summary":"Technetium-99m exametazime (Ceretec, GE Healthcare) is a cold kit reconstituted with the user's own technetium-99m generator eluate. Its FDA-labelled indications are cerebral scintigraphy as an adjunct in the detection of altered regional cerebral perfusion in stroke, and, as a separate use of the same kit, radiolabelling of autologous leukocytes for localising intra-abdominal infection and inflammatory bowel disease; it is approved in adults and in paediatric patients aged 2-17. It is a much older, non-specific perfusion agent rather than a targeted molecular tracer: unlike the amyloid, tau and dopamine transporter tracers in this group, HMPAO shows blood flow, not a disease-specific molecular target.\n\nFor cerebral scintigraphy the FDA label recommends 370-740 MBq (10-20 mCi) intravenously, with dynamic imaging in the first 10 minutes and static (planar or SPECT) imaging from 15 minutes up to 6 hours after injection; an SNMMI fact sheet on the brain-death application cites a higher adult range of 370-1110 MBq (10-30 mCi). For leukocyte labelling the recommended adult dose is 185-370 MBq (5-10 mCi) of labelled cells, re-injected within about an hour of labelling. Effective dose at the upper cerebral dose of 1110 MBq is roughly 10.3 mSv.\n\nBeyond its labelled stroke indication, Tc-99m HMPAO brain SPECT is used clinically, per SNMMI practice guidance, as an ancillary test to help confirm the absence of cerebral blood flow in patients with an equivocal clinical diagnosis of brain death, a use it shares conceptually with EEG and cerebral angiography. It has also historically been used for perfusion patterns in dementia work-up, but F-18 FDG PET has largely superseded SPECT perfusion imaging for that purpose because of better spatial resolution and more extensive validation.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Ceretec (technetium Tc99m exametazime kit)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019829s034lbl.pdf"},{"label":"SNMMI fact sheet: brain death assessment with Ceretec (Tc-99m HMPAO)","url":"https://snmmi.org/common/Uploaded%20files/Web/Education%20and%20Meetings/SNMMI%20Fact%20Sheet_Brain%20Death%20Fact%20Sheet%20Ceretec%20-Tc-99m%20HMPAO.pdf"}],"tags":["SPECT","diagnostic","neurology","perfusion imaging"],"related":["ge-healthcare","spect","f-18-fdg-brain","f-18","tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Ceretec","modality":"SPECT tracer","mechanism":"A lipophilic technetium-99m complex of hexamethylpropyleneamine oxime (HMPAO/exametazime) that crosses the intact blood-brain barrier, is trapped intracellularly by conversion to a hydrophilic species, and distributes in proportion to regional cerebral blood flow, allowing SPECT mapping of brain perfusion.","approvals":[{"region":"US","year":1994,"indication":"Cerebral scintigraphy as an adjunct in the detection of altered regional cerebral perfusion in stroke; and leukocyte-labelled scintigraphy for localising intra-abdominal infection and inflammatory bowel disease"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection (cerebral scintigraphy) or re-injection of labelled autologous leukocytes","schedule":"Cerebral scintigraphy: 370-740 MBq (10-20 mCi) IV; imaging 15 minutes to 6 hours post-injection. Leukocyte labelling: 185-370 MBq (5-10 mCi) of labelled cells, given within about 1 hour of labelling","monitoring":"Visual/semi-quantitative assessment of regional cerebral perfusion on planar or SPECT images","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019829s034lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tc-99m-hmpao-brain/"}
{"id":"f-18-fdg-brain","kind":"drug","name":"Fludeoxyglucose F-18 (brain metabolism)","aka":["FDG-PET brain","18F-FDG"],"tldr":"The standard PET tracer for measuring how the brain is using energy; a pattern of low activity in particular brain regions can help doctors work out which type of dementia a patient has.","summary":"Fludeoxyglucose F-18 (FDG) is the general-purpose PET metabolic tracer used across oncology, cardiology and neurology; it is not brain-specific as a product, but brain FDG PET is a distinct, well-established clinical application. Reduced glucose metabolism follows a regional pattern that differs by disease: temporoparietal and posterior cingulate hypometabolism is typical of Alzheimer's disease, while frontal and/or anterior temporal hypometabolism points to frontotemporal dementia, and this pattern difference is the main clinical use of FDG-PET in cognitive impairment.\n\nIn the United States, Medicare's national coverage determination for FDG-PET in dementia (NCD 220.6.13) covers a scan specifically to help differentiate Alzheimer's disease from frontotemporal dementia, in patients with a recent dementia diagnosis and at least 6 months of documented cognitive decline whose presentation leaves this distinction clinically uncertain after a comprehensive specialist evaluation; a prior brain SPECT or FDG-PET scan for the same question generally precludes a repeat scan within a year. All other dementia uses of FDG-PET (for example distinguishing other neurodegenerative diseases, or use outside a CMS-approved clinical trial in mild cognitive impairment) remain nationally non-covered under this determination, a materially narrower coverage pathway than the one now in force for amyloid PET.\n\nFDG-PET brain imaging does not require thyroid blockade or specialised handling beyond standard F-18 PET radiopharmacy practice, and dosing follows general oncologic/neurologic FDG protocols (typically around 185-370 MBq IV, imaging beginning about 30-45 minutes later, with the patient resting quietly in a darkened, low-stimulation room during uptake to standardise regional brain activity). Because FDG uptake reflects neuronal activity rather than a specific pathological protein, it complements rather than replaces amyloid and tau PET: FDG shows the functional consequence of neurodegeneration, while amyloid and tau tracers show the underlying molecular pathology.","status":"approved","asOf":"2026-09-22","links":[{"label":"CMS NCD 220.6.13: FDG PET for Dementia and Neurodegenerative Diseases","url":"https://www.cms.gov/regulations-and-guidance/guidance/transmittals/downloads/r24ncd.pdf"},{"label":"CMS coding article: PET scan coverage reference table including FDG dementia indication (A53134)","url":"https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=53134"}],"tags":["FDG PET","diagnostic","neurology","metabolic imaging"],"related":["alzheimers-disease","fludeoxyglucose-f18","fdg-pet","tc-99m-hmpao-brain","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"PET tracer","mechanism":"A glucose analogue labelled with fluorine-18 that is taken up by cells in proportion to glucose metabolism and trapped after phosphorylation; in the brain, regional FDG uptake reflects synaptic activity, so characteristic patterns of reduced metabolism can distinguish different neurodegenerative diseases.","approvals":[{"region":"US","year":2004,"indication":"FDG-PET nationally covered by Medicare specifically to differentiate Alzheimer's disease from frontotemporal dementia in patients with an uncertain diagnosis after comprehensive specialist evaluation (NCD 220.6.13)"}],"mechanismSteps":[],"dosing":{"route":"Intravenous injection","schedule":"Typical adult brain FDG-PET protocol: ~185-370 MBq IV, patient rested in a quiet, dimly lit room during the ~30-45 minute uptake phase, then PET imaging","monitoring":"Visual and statistical/voxel-based comparison of regional glucose metabolism against normative databases to identify disease-specific hypometabolism patterns","source":"https://www.cms.gov/regulations-and-guidance/guidance/transmittals/downloads/r24ncd.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/f-18-fdg-brain/"}
{"id":"y-90-resin-microspheres","kind":"drug","name":"Yttrium-90 resin microspheres","aka":["SIR-Spheres","Y-90 resin microspheres"],"tldr":"Tiny radioactive beads are injected through a small tube into the artery that feeds the liver. They lodge in the tumour and give it radiation from the inside, mostly sparing the rest of the liver.","summary":"SIR-Spheres are yttrium-90-loaded resin microspheres delivered by transarterial radioembolisation (TARE/SIRT). Yttrium-90 is a pure beta emitter with a physical half-life of about 64 hours; delivery via the hepatic artery exploits the fact that liver tumours draw most of their blood supply from that vessel while normal liver parenchyma relies more on the portal vein.\n\nThe device holds the original 2002 FDA premarket approval (PMA P990065) for unresectable metastatic liver tumours from primary colorectal cancer, given together with adjuvant intrahepatic artery chemotherapy (floxuridine, FUDR). In July 2025 the FDA approved a labelling supplement extending the indication to local tumour control of unresectable hepatocellular carcinoma (HCC) in patients with no macrovascular invasion, Child-Pugh A cirrhosis, well-compensated liver function and good performance status, making SIR-Spheres the only US radioembolisation product approved for both indications.\n\nDosing is individualised: activity is planned using body-surface-area or partition (MIRD) dosimetry models with pre-treatment angiography and a technetium-99m macroaggregated albumin scan to check lung shunting before the therapeutic infusion. SIR-Spheres also carry regulatory approval in the EU (2002), Canada (2016), Australia (1998) and other markets.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA PMA P990065/S014 approval order","url":"https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?ID=P990065S014"},{"label":"FDA: Summary of safety and effectiveness data (HCC supplement)","url":"https://www.accessdata.fda.gov/cdrh_docs/pdf/P990065S014B.pdf"},{"label":"Sirtex: FDA approval for HCC indication (7 July 2025)","url":"https://www.sirtex.com/media/p1kjiw5m/sirtex-medical-announces-fda-approval-hcc-indication-us.pdf"},{"label":"FDA: original SSED for colorectal indication (2002)","url":"https://www.accessdata.fda.gov/cdrh_docs/pdf/p990065b.pdf"}],"tags":["radioembolisation","liver","beta emitter"],"related":["y-90-glass-microspheres","ho-166-microspheres","tc-99m-maa","tc-99m","y-90"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":["sirtex"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"SIR-Spheres","modality":"radioembolisation","mechanism":"Biocompatible resin microspheres (20-40 micron diameter) carrying yttrium-90, a pure beta emitter, infused through a catheter into the hepatic artery so they lodge preferentially in the hypervascular tumour bed and irradiate it from within while sparing most healthy liver.","approvals":[{"region":"US","year":2002,"indication":"Unresectable metastatic liver tumours from primary colorectal cancer, with adjuvant intrahepatic artery chemotherapy (FUDR)"},{"region":"US","year":2025,"indication":"Local tumour control of unresectable hepatocellular carcinoma (no macrovascular invasion, Child-Pugh A, well-compensated liver function, good performance status)"}],"mechanismSteps":[],"dosing":{"route":"Intra-arterial infusion into the hepatic artery via catheter","schedule":"Single administration per treated liver territory; activity individualised by body-surface-area or partition-model dosimetry","monitoring":"Pre-treatment angiography and 99mTc-MAA lung-shunt scan; post-treatment imaging for dosimetry","source":"https://www.accessdata.fda.gov/cdrh_docs/pdf/P990065S014B.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/y-90-resin-microspheres/"}
{"id":"y-90-glass-microspheres","kind":"drug","name":"Yttrium-90 glass microspheres","aka":["TheraSphere","Y-90 glass microspheres"],"tldr":"Microscopic glass beads containing a radioactive metal are injected into the artery that supplies a liver tumour. The beads stay in place permanently and give off radiation that fades away within about two weeks.","summary":"TheraSphere consists of yttrium-90 fused into glass microspheres and delivered by selective internal radiation therapy (SIRT) through a hepatic artery catheter. It was marketed in the US from 1999-2000 under a Humanitarian Device Exemption (HDE H980006) for unresectable hepatocellular carcinoma (HCC), which limited annual patient numbers.\n\nBoston Scientific (which acquired the product from BTG/Biocompatibles) received full FDA premarket approval (PMA P200029) on 17 March 2021, based on the LEGACY study, a retrospective single-arm, multicentre study of 162 patients with solitary unresectable HCC (1-8 cm). The approved indication is SIRT for local tumour control of solitary tumours 1-8 cm in diameter in patients with Child-Pugh A cirrhosis, no macrovascular invasion and good performance status. LEGACY reported an objective response rate of 72.2% by blinded independent central review and a 76.1% six-month duration-of-response rate.\n\nA post-approval study (multi-compartment dosimetry, MCD-HCC) is ongoing, and a further PMA supplement was cleared by FDA in February 2026. Dosing uses partition-model or MIRD dosimetry to target roughly 100 Gy to the treated liver volume; the microspheres remain permanently implanted.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA: TheraSphere P200029 approval page","url":"https://www.fda.gov/medical-devices/recently-approved-devices/theraspheretm-p200029"},{"label":"FDA: Summary of safety and effectiveness data (P200029)","url":"https://www.accessdata.fda.gov/cdrh_docs/pdf20/P200029B.pdf"},{"label":"Boston Scientific: FDA approval press release, 18 March 2021","url":"https://news.bostonscientific.com/2021-03-18-Boston-Scientific-Receives-FDA-Approval-for-TheraSphere-TM-Y-90-Glass-Microspheres"},{"label":"LEGACY study, Hepatology 2021","url":"https://journals.lww.com/hep/fulltext/2021/11000/yttrium_90_radioembolization_for_the_treatment_of.9.aspx"}],"tags":["radioembolisation","liver","beta emitter"],"related":["y-90-resin-microspheres","ho-166-microspheres","y-90"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":["boston-scientific"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"TheraSphere","modality":"radioembolisation","mechanism":"Insoluble glass microspheres (15-35 micron diameter) with yttrium-90 built into the glass matrix, infused through a hepatic artery catheter. The spheres remain permanently embedded in the liver and deliver beta radiation locally; about 95% of the yttrium-90 dose is absorbed within roughly 12 days given the isotope's short half-life.","approvals":[{"region":"US","year":2021,"indication":"Selective internal radiation therapy (SIRT) for local tumour control of solitary unresectable HCC (1-8 cm), Child-Pugh A cirrhosis, no macrovascular invasion, good performance status"}],"mechanismSteps":[],"dosing":{"route":"Intra-arterial infusion into the hepatic artery via catheter","schedule":"Single administration per treated liver territory, individualised by partition-model dosimetry aiming for a target absorbed dose","source":"https://www.accessdata.fda.gov/cdrh_docs/pdf20/P200029B.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/y-90-glass-microspheres/"}
{"id":"ho-166-microspheres","kind":"drug","name":"Holmium-166 microspheres","aka":["QuiremSpheres","166Ho-PLLA microspheres"],"tldr":"Tiny plastic beads carrying a radioactive, slightly magnetic metal are injected into the artery feeding a liver tumour. Because the metal shows up on both nuclear scans and MRI, doctors can check exactly where the beads went.","summary":"QuiremSpheres are holmium-166-labelled poly-L-lactic acid microspheres for radioembolisation (SIRT) of unresectable liver tumours, developed at University Medical Center Utrecht and commercialised by Quirem Medical (later acquired by Terumo). Holmium-166 has a physical half-life of 26.8 hours, so more than 90% of the radiation dose is delivered within the first four days after administration.\n\nThe product received CE marking as an active implantable medical device in April 2015, and a matching low-activity test dose (QuiremScout, identical size and shape) was CE-marked in 2018-2019 to predict lung shunting and biodistribution before therapy. Holmium-166 emits both beta particles (for therapy) and a gamma photon, and is paramagnetic, which allows quantitative SPECT and MRI-based dosimetry after treatment, alongside the more usual post-treatment imaging used for yttrium-90 products.\n\nQuiremSpheres has not obtained FDA approval and is used in Europe and other CE-mark-recognising markets; NICE (UK) technology appraisal TA985 reviewed its use in advanced HCC. It is one of three commercially available liver radioembolisation microsphere products, alongside the yttrium-90 resin (SIR-Spheres) and glass (TheraSphere) microspheres.","status":"approved","asOf":"2026-09-22","links":[{"label":"Holmium-166 radioembolisation: current status and future perspectives, PMC 2022","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9626412/"},{"label":"NICE TA985: QuiremSpheres for advanced HCC","url":"https://www.nice.org.uk/guidance/ta985/chapter/2-Information-about-QuiremSpheres"},{"label":"Terumo: QuiremScout CE mark announcement, 2019","url":"https://www.terumo.com/newsrelease/detail/20190107/234"}],"tags":["radioembolisation","liver","beta emitter","CE mark"],"related":["y-90-resin-microspheres","y-90-glass-microspheres","y-90","ho-166"],"indications":["hcc"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"QuiremSpheres","modality":"radioembolisation","mechanism":"Poly-L-lactic acid (PLLA) microspheres loaded with holmium-166 (a beta emitter that also emits an imageable gamma photon and is paramagnetic, so uptake can be checked on SPECT or MRI as well as CT), infused through a hepatic artery catheter to treat unresectable liver tumours.","approvals":[{"region":"EU","year":2015,"indication":"Treatment of unresectable liver tumours (radioembolisation)"}],"mechanismSteps":[],"dosing":{"route":"Intra-arterial infusion into the hepatic artery via catheter","schedule":"Single administration, typically with a QuiremScout test dose beforehand for dosimetry","source":"https://www.nice.org.uk/guidance/ta985/chapter/2-Information-about-QuiremSpheres"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ho-166-microspheres/"}
{"id":"i-131-tositumomab","kind":"drug","name":"Iodine-131 tositumomab","aka":["Bexxar","tositumomab and I-131 tositumomab"],"tldr":"A cancer-targeting antibody carrying a radioactive form of iodine was used, as a single course, to treat a type of blood cancer called non-Hodgkin lymphoma. The manufacturer stopped selling it in 2014 because too few patients were using it.","summary":"The Bexxar therapeutic regimen combined tositumomab, an anti-CD20 murine IgG2a monoclonal antibody, with the same antibody radiolabelled with iodine-131. It was approved by the FDA in 2003 (and in Canada in 2005) for CD20-positive relapsed or refractory low-grade, follicular or transformed non-Hodgkin lymphoma in patients who had progressed during or after rituximab therapy, including rituximab-refractory disease. It was given as a single course only, comprising an unlabelled predose followed by a dosimetric and then a therapeutic dose of 131I-tositumomab, with activity individualised to deliver a specified total-body radiation dose.\n\nBexxar competed with the similar CD20-targeted radioimmunotherapy ibritumomab tiuxetan (Zevalin, labelled with yttrium-90). Despite comparable efficacy, Bexxar's use declined steadily after a 2006 peak: by 2012 only about 75 US patients received it in a year. GlaxoSmithKline announced in August 2013 that it would discontinue manufacture and sale of the regimen, citing projected declining sales and the availability of alternative therapies; marketing was formally withdrawn on 20 February 2014.\n\nBexxar is a useful cautionary example in the graph: an approved, effective radiopharmaceutical regimen withdrawn for commercial rather than safety reasons, illustrating how logistics (dosimetry visits, hospital nuclear-medicine capacity, competition from simpler agents) can end a therapy's market life even when clinical data support it.","status":"withdrawn","asOf":"2026-09-22","links":[{"label":"GSK: announcement of discontinuation, 6 August 2013","url":"https://pipelinereview.com/gsk-to-discontinue-manufacture-and-sale-of-the-bexxar-therapeutic-regimen-tositumomab-and-iodine-i-131-tositumomab/"},{"label":"JAMA Internal Medicine: Withdrawal of drugs for commercial reasons - tositumomab, 2014","url":"https://static1.squarespace.com/static/55550f38e4b0884d8d80118e/t/5565d1aae4b0660ba5b932e2/1432736170326/2014+-+Nov+-+JAMA+IM+-+Withdrawal+of+Drugs+for+Commercial+Reasons+-+Tositumomab.pdf"},{"label":"The rise and fall of iodine-131 tositumomab: Bexxar's story","url":"https://openmedscience.com/the-rise-and-fall-of-iodine-131-tositumomab-bexxars-story/"}],"tags":["radioimmunotherapy","lymphoma","withdrawn","beta and gamma emitter"],"related":["ibritumomab-tiuxetan","rituximab","i-131","y-90"],"indications":["follicular-lymphoma"],"sections":[],"technologies":["radioimmunotherapy"],"targets":["cd20"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Bexxar","modality":"radioimmunotherapy","mechanism":"An unlabelled anti-CD20 murine monoclonal antibody (tositumomab) dosing step to saturate normal B-cell sinks, followed by the same antibody labelled with iodine-131, which delivers combined beta and gamma radiation directly to CD20-expressing lymphoma cells as well as an antibody-dependent immune effect.","approvals":[{"region":"US","year":2003,"indication":"CD20-positive relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma progressing during or after rituximab therapy"},{"region":"CA","year":2005,"indication":"Same indication as the US approval"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2013-08-06","type":"withdrawal","region":"US/CA","note":"GlaxoSmithKline announced it would discontinue manufacture and sale of the Bexxar regimen, citing declining use (about 75 US patients in 2012) and available alternative therapies.","source":"https://pipelinereview.com/gsk-to-discontinue-manufacture-and-sale-of-the-bexxar-therapeutic-regimen-tositumomab-and-iodine-i-131-tositumomab/"},{"date":"2014-02-20","type":"withdrawal","region":"US/CA","note":"Marketing of the Bexxar therapeutic regimen formally discontinued.","source":"https://openmedscience.com/the-rise-and-fall-of-iodine-131-tositumomab-bexxars-story/"}],"route":"/drugs/i-131-tositumomab/"}
{"id":"sr-89-chloride","kind":"drug","name":"Strontium-89 chloride","aka":["Metastron","Strontium89","89SrCl2"],"tldr":"A radioactive form of strontium is injected into a vein. Because it behaves like calcium, it collects in the damaged, overactive bone around cancer that has spread to bone, and its radiation can relieve bone pain for months.","summary":"Strontium-89 chloride (branded Metastron) is indicated for the relief of bone pain in patients with painful skeletal metastases, confirmed by a prior bone scan; it is not a treatment for the underlying cancer and does not relieve pain from soft tissue disease. The FDA label recommends a fixed dose of 148 MBq (4 mCi) by slow intravenous injection over one to two minutes, or a weight-based alternative of 1.5-2.2 MBq/kg (40-60 microCi/kg); repeat dosing is generally not recommended at intervals of less than 90 days and depends on haematological recovery.\n\nStrontium-89 decays by beta emission with a physical half-life of 50.5 days; roughly two-thirds of excretion is urinary and one-third faecal in patients with bone metastases, with retention in metastatic lesions lasting much longer than the roughly 14-day turnover in normal bone. Pain relief typically begins 10-20 days after injection and can last three to six months; a transient pain flare in the first few days is common.\n\nMetastron was originally marketed by Amersham/Zeneca and later GE Healthcare; the branded product was discontinued and the compound is now supplied generically (marketed as Strontium89). It sits alongside samarium-153 lexidronam and radium-223 dichloride as FDA/EMA-approved bone-palliation radiopharmaceuticals, though 89Sr and 153Sm are not tumour-type-restricted the way radium-223's label is limited to castration-resistant prostate cancer.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Metastron (strontium-89 chloride injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020134s012lbl.pdf"},{"label":"SNMMI/EANM procedure guideline for palliative radionuclide bone therapies, 2023","url":"https://tech.snmjournals.org/content/51/3/176"}],"tags":["bone pain palliation","beta emitter","calcium mimetic"],"related":["radium-223","samarium-153-lexidronam","bone-metastases","ra-223","sm-153","sr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Metastron","modality":"radioligand therapy","mechanism":"Strontium-89 chloride is a calcium-mimetic, bone-seeking beta emitter given by intravenous injection. It behaves like calcium, clearing from blood and localising preferentially in bone mineral at sites of active osteogenesis, so blastic metastatic lesions accumulate far more strontium than normal bone and receive a higher local radiation dose that palliates pain.","approvals":[{"region":"US","year":1993,"indication":"Relief of bone pain in patients with painful skeletal metastases (presence of bone metastases must be confirmed prior to therapy)"}],"mechanismSteps":[],"dosing":{"route":"Slow intravenous injection (1-2 minutes)","schedule":"148 MBq (4 mCi) fixed dose, or 1.5-2.2 MBq/kg (40-60 microCi/kg); repeat doses generally not within 90 days, based on response and haematological status","monitoring":"Blood counts (platelets, neutrophils) before and after treatment; confirm blastic bone metastases on bone scan before therapy","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020134s012lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/sr-89-chloride/"}
{"id":"re-188-sct","kind":"drug","name":"Rhenium-188 skin cancer therapy","aka":["Rhenium-SCT","188Re epidermal radionuclide therapy"],"tldr":"A radioactive paste is spread over a thin film placed on top of a skin cancer. The radiation only travels a few millimetres, so it treats the visible tumour without surgery, cutting, or affecting deeper tissue.","summary":"Rhenium-SCT (Skin Cancer Therapy) is a non-invasive, single-session epidermal brachytherapy for non-melanoma skin cancer (basal cell carcinoma and cutaneous squamous cell carcinoma), developed by OncoBeta. Rhenium-188 (half-life about 17 hours) is produced on demand from a tungsten-188/rhenium-188 generator and formulated as a resin that is applied to an adhesive foil placed over the lesion, so the radioactive material never directly contacts the skin. A typical prescribed dose is 50 Gy to the deepest point of the lesion (target depth up to about 3 mm).\n\nThe device and compound are registered in Australia (ARTG, class IIb, from 2020-2022) and hold CE marking, with use reported across Europe, the UK, New Zealand and South Africa; it does not have FDA approval. A single-arm, multicentre phase 4 post-marketing study (EPIC-Skin) reported, at 12 months, lesion-based complete response in 94.1% and partial response in 3.2% of 185 evaluable lesions, with no toxicities above CTCAE grade 2 and favourable cosmetic and quality-of-life outcomes; an earlier Italian series (Castellucci et al., EJNMMI Physics) reported 98% complete lesion response at 6 months in 54 evaluable lesions.\n\nBecause treatment is external and the isotope's beta range is only a few millimetres, Rhenium-SCT is positioned for lesions ≤3 mm deep and ≤8 cm2 in difficult-to-treat cosmetic or functional sites (nose, ear, lip, digits, genitals) where surgery or conventional external-beam radiotherapy is less attractive.","status":"approved","asOf":"2026-09-22","links":[{"label":"OncoBeta: Rhenium-SCT technology overview","url":"https://www.oncobeta.com/technology/"},{"label":"EPIC-Skin phase 4 study, 12-month results (PMC, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12197855/"},{"label":"Castellucci et al., high-dose brachytherapy with non-sealed 188Re for non-melanoma skin cancer, EJNMMI","url":"https://www.healthcert.com/hubfs/EJNMMI%20Castellucci%20-%20Savoia%20et%20al.%202020.pdf"},{"label":"Australian MSAC public summary document on Rhenium-188 brachytherapy for skin cancer","url":"https://www.msac.gov.au/sites/default/files/2025-07/1657.1_final_psd_-_april_2025_-_redacted.pdf"}],"tags":["brachytherapy","skin cancer","beta emitter","non-invasive"],"related":["re-188"],"indications":[],"sections":[],"technologies":["ldr-seed-brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Rhenium-SCT","modality":"brachytherapy source","mechanism":"A resin containing the beta- and gamma-emitting radioisotope rhenium-188 is applied directly to the skin over a thin protective foil moulded to the shape of a non-melanoma skin lesion. Beta particles penetrate only a few millimetres, delivering a high local dose to the tumour (about 92% of the dose within 2 mm) while a single outpatient application typically lasts under an hour.","approvals":[{"region":"EU/UK/AU/NZ/ZA","year":2015,"indication":"Shallow (≤3 mm deep) basal cell carcinoma and squamous cell carcinoma without perineural invasion or high-risk pathology","note":"CE marking and national device registrations; not FDA approved"}],"mechanismSteps":[],"dosing":{"route":"Topical epidermal application (resin on adhesive foil placed over the lesion)","schedule":"Single outpatient session, typically prescribing 50 Gy to the deepest point of the lesion","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12197855/"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/re-188-sct/"}
{"id":"lu-177-pnt2002","kind":"drug","name":"Lutetium-177 PNT2002","aka":["177Lu-PNT2002","177Lu-PSMA-I&T (POINT/Lantheus)"],"tldr":"A radioactive drug that homes in on a marker found on most prostate cancer cells, delivering radiation directly to the tumour, is being tested as a treatment for prostate cancer that has stopped responding to hormone therapy.","summary":"177Lu-PNT2002 is a PSMA-targeted radioligand therapy built on the PSMA-I&T ligand, labelled with beta-emitting no-carrier-added lutetium-177. POINT Biopharma developed it and Lantheus in-licensed exclusive worldwide commercial rights (excluding certain Asian territories) in December 2022; POINT was subsequently acquired by Eli Lilly. The FDA granted Fast Track designation for metastatic castration-resistant prostate cancer (mCRPC) in April 2023.\n\nThe pivotal phase 3 SPLASH trial (NCT04647526) randomised 412 patients with PSMA-expressing mCRPC who had progressed on an androgen receptor pathway inhibitor (ARPI) and refused or were ineligible for chemotherapy, 2:1 to 177Lu-PNT2002 (up to four cycles, 6.8 GBq per cycle every 8 weeks) versus a change to abiraterone or enzalutamide, with crossover allowed on progression. Topline results (December 2023) showed a statistically significant improvement in radiographic progression-free survival by blinded independent central review: median 9.5 months with 177Lu-PNT2002 versus 6.0 months with ARPI (HR 0.71, p=0.0088); overall survival was immature, with an interim HR of 1.11, and 84.6% of control-arm patients who progressed crossed over. Grade 3+ treatment-emergent adverse events, serious adverse events and discontinuations for toxicity were all numerically lower on 177Lu-PNT2002 than on ARPI.\n\nAs of the March 2026 status, 177Lu-PNT2002 has not received a marketing authorisation in any jurisdiction; further follow-up data were expected in 2024 ahead of a potential US new drug application.","status":"phase-3","asOf":"2026-09-22","links":[{"label":"Lantheus/POINT: positive topline SPLASH results, 18 December 2023","url":"https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-and-point-biopharma-announce-positive-topline-results"},{"label":"FDA Fast Track designation announcement, 24 April 2023","url":"https://investor.lantheus.com/node/14596/pdf"},{"label":"Initial clinical experience with 177Lu-PNT2002 (SPLASH lead-in), PMC 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11745944/"},{"label":"ClinicalTrials.gov: SPLASH (NCT04647526)","url":"https://clinicaltrials.gov/study/NCT04647526"}],"tags":["PSMA","radioligand therapy","prostate cancer","beta emitter","phase 3"],"related":["pluvicto","lu177-psma-it","lu-177"],"indications":["prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":["lantheus","point-biopharma","eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":["splash"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"PNT2002","modality":"radioligand therapy","mechanism":"A PSMA-targeted small-molecule ligand (PSMA-I&T) labelled with no-carrier-added lutetium-177, a beta emitter, delivering targeted radiation to PSMA-expressing prostate cancer cells after intravenous infusion.","approvals":[],"mechanismSteps":[],"dosing":{"route":"Intravenous infusion","schedule":"Up to 4 cycles at 6.8 GBq (±10%) per cycle, every 8 weeks (SPLASH trial regimen)","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11745944/"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/lu-177-pnt2002/"}
{"id":"tlx-591","kind":"drug","name":"Lutetium-177 rosopatamab tetraxetan","aka":["TLX591","TLX591-Tx","177Lu-rosopatamab tetraxetan"],"tldr":"A cancer-targeting antibody carrying a radioactive metal is being tested as a two-dose treatment for advanced prostate cancer, on top of the usual hormone or chemotherapy drugs.","summary":"TLX591 (INN lutetium Lu 177 rosopatamab tetraxetan; also referred to as TLX591-Tx) is Telix Pharmaceuticals' lead PSMA-targeted radio-antibody-drug conjugate for metastatic castration-resistant prostate cancer (mCRPC). Unlike small-molecule PSMA ligands (e.g. PSMA-617, PSMA-I&T), TLX591 uses a full-length PSMA-targeting monoclonal antibody, given as two 76 mCi intravenous infusions 14 days apart; its hepatic (rather than renal) clearance means long-term follow-up has not shown significant acute or delayed nephrotoxicity.\n\nBy the ProstACT SELECT trial (NCT04786847), 242 patients had been treated with TLX591 across eight phase 1/2 studies; SELECT itself reported a median radiographic progression-free survival of 8.8 months in 23 evaluable mCRPC patients, and an earlier single-arm phase 2 study reported 42.3-month overall survival in 17 patients dosed under a fractionated regimen with concurrent docetaxel.\n\nThe pivotal phase 3 ProstACT Global trial (ClinicalTrials.gov NCT06520345) compares TLX591-Tx plus standard of care (abiraterone, enzalutamide or docetaxel) against standard of care alone in PSMA-positive mCRPC patients who progressed on one prior ARPI, with an initial 36-patient safety/dosimetry lead-in (Part 1) followed by a 2:1 randomised expansion (Part 2, target enrolment approximately 490). Part 1 results (reported March 2026) showed an acceptable safety and tolerability profile across all three standard-of-care combination cohorts, with no new safety signals; the main non-haematological toxicities were fatigue, nausea and dry mouth, and haematological toxicity (thrombocytopenia, neutropenia) was transient and manageable. Part 2 is enrolling in Australia, New Zealand, Canada, Türkiye, the UK and other jurisdictions; TLX591 has not yet received marketing authorisation anywhere.","status":"phase-3","asOf":"2026-09-22","links":[{"label":"Telix: first patient dosed in ProstACT GLOBAL Phase 3","url":"https://telixpharma.com/news-views/first-patient-dosed-in-phase-iii-prostact-global-study-of-antibody-based-prostate-cancer-therapy-candidate-tlx591/"},{"label":"Telix: ProstACT Global Part 1 achieves primary objectives, 9 March 2026","url":"https://telixpharma.com/news-views/prostact-global-phase-3-study-part-1-achieves-primary-objectives/"},{"label":"Telix: positive rPFS data from ProstACT SELECT trial","url":"https://telixpharma.com/wp-content/uploads/2024/05/TLX_ProstACT_SELECT_Study_of_TLX591_rADC_Therapy_Positive_rPFS.pdf"},{"label":"ClinicalTrials.gov: ProstACT Global (NCT06520345)","url":"https://clinicaltrials.gov/study/NCT06520345"}],"tags":["PSMA","radio-antibody-drug conjugate","prostate cancer","phase 3"],"related":["illuccix","pluvicto","lu-177"],"indications":["prostate-mcrpc"],"sections":[],"technologies":["radioimmunotherapy"],"targets":["psma"],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06520345"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"TLX591","modality":"radioimmunotherapy","mechanism":"A radio-antibody-drug conjugate (rADC): a high-specificity PSMA-targeting monoclonal antibody, linked via a chelator to cytotoxic lutetium-177, given intravenously. Because it is a full antibody rather than a small molecule, it has longer tumour retention and different biodistribution to small-molecule PSMA radioligands, with lower observed uptake in kidneys, salivary and lacrimal glands.","approvals":[],"mechanismSteps":[],"dosing":{"route":"Intravenous infusion","schedule":"Two doses of 76 mCi, 14 days apart, per treatment course","source":"https://telixpharma.com/wp-content/uploads/2024/05/TLX_ProstACT_SELECT_Study_of_TLX591_rADC_Therapy_Positive_rPFS.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/tlx-591/"}
{"id":"pb-212-vmt-alpha-net","kind":"drug","name":"Lead-212 VMT-alpha-NET","aka":["212Pb-VMT-alpha-NET","[212Pb]VMT-α-NET","203Pb-VMT-alpha-NET (imaging analogue)"],"tldr":"A drug that targets a marker on neuroendocrine tumour cells is being tested with two versions of a radioactive metal: one lets doctors see where the tumour is on a scan, and the other delivers a strong, short-range dose of radiation to kill the tumour cells.","summary":"VMT-alpha-NET is Perspective Therapeutics' targeted alpha-particle therapy (TAT) programme for somatostatin receptor subtype 2 (SSTR2)-expressing neuroendocrine tumours (NETs), pheochromocytoma/paraganglioma and meningioma. The same peptide is labelled with lead-203 for SPECT/CT imaging (used to plan a patient-specific kidney radiation-dose limit) and with the alpha-emitting isotope lead-212 for therapy.\n\nThe ongoing multicentre, open-label phase 1/2a trial (ClinicalTrials.gov NCT05636618) is a dose-escalation and dose-expansion study in up to about 300 adult, PRRT-naive patients with unresectable or metastatic SSTR2-positive NETs, bronchial NETs, pheochromocytoma/paraganglioma, or meningioma; dosing is by intravenous infusion roughly every 8 weeks. The FDA granted Fast Track designation in September 2022 for SSTR2-positive NETs regardless of prior treatment. A separate single-centre phase 1 study in PRRT-refractory patients (NCT06148636) is under way at the University of Iowa.\n\nInterim data presented at ASCO-GI and AACR in 2026 (data cut-offs through April 2026) reported, across dose cohorts up to 64 patients, no dose-limiting toxicities, treatment-related discontinuations or grade 5 events, with grade 3+ adverse events in roughly a third of patients (mostly non-renal, non-myelosuppressive); in evaluable patients from the lower dose cohorts, 76% remained progression-free and alive, and an objective response rate of about 39-44% (RECIST v1.1) was reported in Cohort 2 (5 mCi per dose). VMT-alpha-NET has not received marketing authorisation in any jurisdiction; the programme is still determining its recommended phase 2 dose.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Perspective Therapeutics: VMT-alpha-NET pipeline page","url":"https://perspectivetherapeutics.com/pipeline/vmt-alpha-net"},{"label":"ClinicalTrials.gov: NCT05636618","url":"https://clinicaltrials.gov/study/NCT05636618"},{"label":"Perspective Therapeutics: updated interim data at AACR 2026","url":"https://www.globenewswire.com/news-release/2026/04/20/3276793/0/en/perspective-therapeutics-presents-updated-interim-data-of-212pb-vmt-%CE%B1-net-in-its-ongoing-phase-1-2a-clinical-trial-at-the-2026-aacr-annual-meeting.html"},{"label":"Perspective Therapeutics: first patient dosed press release, 2023","url":"https://perspectivetherapeutics.com/pr/perspective-therapeutics-announces-first-patient-dosed-in-a-phase-1-study-of-212pbvmtnet-to-treat-refractory-or-relapsedneuroendocrine-tumors"}],"tags":["alpha therapy","SSTR2","neuroendocrine tumours","lead-212","phase 1/2"],"related":["alphamedix","itm-11","lutathera","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["sstr2"],"drugs":[],"companies":["perspective-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05636618"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"VMT-alpha-NET","modality":"alpha therapy","mechanism":"A somatostatin receptor subtype 2 (SSTR2)-targeting peptide that can be radiolabelled either with lead-203 (a gamma emitter, for SPECT imaging and dosimetry planning) or with lead-212 (an in-vivo alpha-emitter generator via its decay chain), delivering high-linear-energy-transfer alpha radiation directly to SSTR2-expressing neuroendocrine tumour cells.","approvals":[],"mechanismSteps":[],"dosing":{"route":"Intravenous infusion","schedule":"Dose-escalation cohorts from 2.5 to 6.0 mCi per dose, approximately every 8 weeks, up to 4 administrations","source":"https://www.globenewswire.com/news-release/2026/04/20/3276793/0/en/perspective-therapeutics-presents-updated-interim-data-of-212pb-vmt-%CE%B1-net-in-its-ongoing-phase-1-2a-clinical-trial-at-the-2026-aacr-annual-meeting.html"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/pb-212-vmt-alpha-net/"}
{"id":"lu-177-dotatate-generic","kind":"drug","name":"Lutetium-177 dotatate (radioligand equivalent)","aka":["Bexlutry","generic lutetium Lu 177 dotatate"],"tldr":"A second, cheaper version of an already-approved radioactive drug for neuroendocrine tumours has been approved, using the same active radioactive ingredient as the original but made by a different company.","summary":"Bexlutry (lutetium Lu 177 dotatate injection), from Curium, is the first product the FDA has approved as a 'radioligand equivalent' of an existing radiopharmaceutical: it has the same active radiopharmaceutical ingredient as Novartis/Advanced Accelerator Applications' Lutathera. The FDA approved it on 14 September 2026 for adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), spanning foregut, midgut and hindgut tumours.\n\nCurium filed under the FDA's 505(b)(2) pathway in July 2024, relying on published evidence and bridging data demonstrating a similar biological and chemical profile to Lutathera rather than running a new phase 3 trial. Approval followed a June 2026 court decision that cleared Curium of patent-infringement claims brought by Novartis. Unlike Lutathera, whose US label also covers paediatric patients aged 12 and older, Bexlutry's approval is adult-only.\n\nBexlutry is immediately available for prescribing in the US. A second lutetium dotatate candidate, Lantheus's PNT2003, received FDA tentative approval in March 2026 under the abbreviated new drug application (ANDA) pathway but is not yet launched; separately, ITM's related product 177Lu-edotreotide (ITM-11) received an FDA complete response letter in August 2026 over manufacturing and third-party facility issues unrelated to its clinical data. Bexlutry's approval is the first time a radioligand therapy for cancer has faced this kind of direct, lower-cost competition in the US market.","status":"approved","asOf":"2026-09-27","links":[{"label":"Drugs@FDA: NDA 218525, Bexlutry (lutetium Lu 177 dotatate)","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218525"},{"label":"Curium: FDA approval of BEXLUTRY, 14 September 2026","url":"https://www.curiumpharma.com/2026/09/14/fda-approval-bexlutry/"},{"label":"FiercePharma: FDA approves first radioligand equivalent","url":"https://www.fiercepharma.com/pharma/fda-approves-first-radioligand-equivalent-curiums-copycat-novartis-lutathera"},{"label":"MedPath: FDA approves Curium's Bexlutry, first generic radioligand","url":"https://trial.medpath.com/news/fda-approves-curium-s-bexlutry-first-generic-radioligand-challenging-lutathera-s-gep-net-monopoly"}],"tags":["radioligand therapy","generic","neuroendocrine tumours","beta emitter"],"related":["lutathera","itm-11","lu-177"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":["radioligand-therapy","prrt"],"targets":["sstr2"],"drugs":[],"companies":["curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Bexlutry","modality":"radioligand therapy","mechanism":"A somatostatin analogue (DOTATATE) labelled with beta-emitting lutetium-177, delivering targeted radiation to somatostatin receptor-positive neuroendocrine tumour cells; chemically and biologically the same active ingredient as Lutathera, approved through the FDA's 505(b)(2) route as a radioligand equivalent rather than through a new pivotal efficacy trial.","approvals":[{"region":"US","year":2026,"indication":"Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), including foregut, midgut and hindgut tumours, in adults","note":"Approved via the FDA 505(b)(2) pathway as a radioligand equivalent of Lutathera, 14 September 2026"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2026-09-14","type":"approval","region":"US","note":"Bexlutry, NDA 218525 (Curium), original approval; FDA classification Type 5 new formulation or new manufacturer, standard review","source":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218525"}],"route":"/drugs/lu-177-dotatate-generic/"}
{"id":"i-125-seeds","kind":"drug","name":"Iodine-125 brachytherapy seeds","aka":["I-125 seeds","125I permanent seed implants"],"tldr":"Tiny metal seeds containing a mildly radioactive form of iodine are permanently placed inside a tumour, most often the prostate, where they slowly release radiation over several months and then become harmless.","summary":"Iodine-125 brachytherapy seeds are titanium-encapsulated radionuclide sources used mainly for permanent low-dose-rate (LDR) interstitial brachytherapy of localised prostate cancer, and also for other accessible tumours of the head and neck, lung, pancreas and elsewhere, either as primary treatment or for residual disease after surgery. In the US, seeds such as Theragenics' I-Seed, Implant Sciences' I-Plant and similar products are cleared through the FDA's 510(k) premarket notification pathway (product code KXK, 21 CFR 892.5730) as substantially equivalent to earlier cleared brachytherapy sources; brachytherapy as a procedure does not itself require separate FDA approval.\n\nIodine-125 has a 59.4-day physical half-life and a mean photon energy of about 28 keV. For prostate monotherapy, published series correlate a minimum dose covering 90% of the prostate volume (D90) of at least 140 Gy with improved biochemical control; when combined with external-beam radiotherapy the typical prescription is lower, around 108-110 Gy. Seeds are implanted transperineally under transrectal ultrasound (and sometimes fluoroscopic or CT) guidance, either as loose seeds or linked (so-called stranded seeds) at regular intervals, and remain permanently in place, gradually becoming inert as the isotope decays.\n\nIodine-125 competes with palladium-103 and caesium-131 as LDR prostate brachytherapy isotopes; comparative series have found no clear difference in outcomes between iodine-125 and palladium-103 at three years. Because this is a device/source category with many manufacturers rather than a single branded drug, the record here covers the isotope and its clinical use rather than one company's product.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA 510(k) clearance letter: I-Plant Model 3500 iodine-125 brachytherapy seeds","url":"https://www.accessdata.fda.gov/cdrh_docs/pdf2/k023242.pdf"},{"label":"Prostate brachytherapy review, Translational Andrology and Urology 2018","url":"https://cdn.amegroups.cn/journals/amepc/files/journals/3/articles/18019/public/18019-PB1-3327-R2.pdf"}],"tags":["brachytherapy","prostate cancer","gamma/X-ray emitter","permanent implant"],"related":[],"indications":["prostate","prostate-high-risk"],"sections":[],"technologies":["ldr-seed-brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"brachytherapy source","mechanism":"Titanium-encapsulated seeds containing iodine-125, a low-energy gamma/X-ray emitter with a 59.4-day physical half-life, are permanently implanted (typically transperineally into the prostate under ultrasound guidance) to deliver low-dose-rate radiation from within the tumour over several months.","approvals":[],"mechanismSteps":[],"dosing":{"route":"Permanent transperineal interstitial implantation (typically prostate), or interstitial/surface application at other sites","schedule":"Single permanent implant; monotherapy target D90 approximately 140-160 Gy, or approximately 108-110 Gy when combined with external-beam radiotherapy","source":"https://cdn.amegroups.cn/journals/amepc/files/journals/3/articles/18019/public/18019-PB1-3327-R2.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/i-125-seeds/"}
{"id":"ac-225-fpi-2068","kind":"drug","name":"Actinium-225 FPI-2068","aka":["225Ac-FPI-2068","[225Ac]-FPI-2068"],"tldr":"An antibody engineered to grab onto two markers found together on some solid tumours, but not on healthy cells, carries a powerful short-range radioactive payload into the tumour to try to destroy it.","summary":"225Ac-FPI-2068 is a bispecific targeted alpha therapy (TAT) from Fusion Pharmaceuticals, developed jointly with AstraZeneca, designed for solid tumours that co-express EGFR and cMET (including head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer and pancreatic ductal adenocarcinoma). It combines the bispecific antibody FPI-2053 with the alpha emitter actinium-225 via a DOTA chelate; an indium-111-labelled version of the same antibody (FPI-2107) is used as a companion imaging and dosimetry tracer, and unlabelled FPI-2053 is given as a pre-dose to optimise biodistribution.\n\nPreclinical data presented at AACR-NCI-EORTC in 2023 showed FPI-2068 bound EGFR/cMET-expressing colorectal and lung cancer cell lines, internalised into tumour cells, and caused prolonged tumour regression (over 28 days) in xenograft models at doses of 370-740 kBq/kg, with evidence of DNA double-strand break formation and apoptosis consistent with its proposed mechanism. The FDA cleared investigational new drug (IND) applications for FPI-2068 and FPI-2107 in April 2023.\n\nA first-in-human phase 1, two-part, dose-escalation trial (ClinicalTrials.gov NCT06147037) opened in July 2024 across US and Canadian sites, evaluating safety, tolerability, dosimetry, biodistribution and pharmacokinetics in adults with advanced EGFR/cMET-co-expressing solid tumours; Part A optimises the FPI-2053 pre-dose and Part B escalates the actinium-225 dose. As of the most recent public update (October 2025), no human efficacy or safety results had been reported; the study's estimated primary completion is December 2026/2027.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Fusion Pharmaceuticals: AACR-NCI-EORTC 2023 preclinical poster on FPI-2068","url":"https://fusionpharma.com/wp-content/uploads/2023/10/2068_AACR-poster_2023_Final.pdf"},{"label":"Fusion Pharmaceuticals: IND clearance for FPI-2068 and FPI-2107, April 2023","url":"https://www.pharmaceutical-technology.com/news/fusion-fda-ind-fpi-2068/"},{"label":"ClinicalTrials.gov: NCT06147037","url":"https://clinicaltrials.gov/study/NCT06147037"}],"tags":["alpha therapy","bispecific antibody","EGFR","cMET","actinium-225","phase 1"],"related":["fpi-2265","in-111","ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":["fusion-pharma","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["EGFR and cMET are not yet represented as target records in this graph, so no targets[] link is made here; add them once those target records exist."],"code":"FPI-2068","modality":"alpha therapy","mechanism":"A bispecific, humanised IgG antibody (FPI-2053) that binds both EGFR and cMET, conjugated via a DOTA chelator to the alpha-emitting radioisotope actinium-225. Because it targets two receptors that are co-expressed on tumour cells but not usually together on normal tissue, the antibody is designed to internalise preferentially into tumour cells, delivering alpha particles that cause DNA double-strand breaks.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[],"route":"/drugs/ac-225-fpi-2068/"}
{"id":"b-ac225-supply","kind":"bottleneck","name":"Actinium-225 supply","aka":[],"tldr":"There is barely enough of the radioactive metal actinium-225 in the world to treat a few hundred patients a year, even though several new cancer drugs need it. New ways of making it are being built, but they are not yet running at full scale.","summary":"Actinium-225's legacy supply comes from milking thorium-229 'cow' generators held at only four sites worldwide: Oak Ridge National Laboratory (US), the Joint Research Centre in Karlsruhe (Germany), the Institute for Physics and Power Engineering (Russia, irregular), and formerly SCK CEN (Belgium). Together they yield roughly 63 GBq (1.7 Ci) a year, which a 2025 review estimates is enough for only 100 to 200 patient treatments globally, against research and trial demand alone estimated at around 185 GBq (5 Ci) a year.\n\nThe scarcity has already stopped a clinical programme: in June 2024 Bristol Myers Squibb's RayzeBio paused new-patient enrolment in the phase 3 ACTION-1 trial of RYZ101 (225Ac-DOTATATE) specifically because it could not secure enough actinium-225, with the company citing a single global supplier for the trial. Every alpha-emitting PSMA and DOTATATE programme in development competes for the same small pool.\n\nThe fix is a shift from thorium-229 decay to direct production: accelerator irradiation of radium-226 or thorium-232 targets. The US DOE Isotope Program runs a tri-laboratory accelerator effort (Brookhaven, Los Alamos, Oak Ridge); commercial entrants are building cyclotron and electron-accelerator routes using radium-226 stocks. None of these has yet demonstrated tens of curies a year of GMP-grade material, which is the scale several late-stage alpha-emitter programmes will need if they reach approval.","asOf":"2026-09-22","links":[{"label":"Actinium-225/Bismuth-213 as potential leaders for targeted alpha therapy (2025 review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12468084/"},{"label":"FiercePharma: BMS and RayzeBio halt radiotherapy trial enrollment after isotope runs scarce","url":"https://www.fiercepharma.com/pharma/bms-and-rayzebio-halt-radiotherapy-trial-enrollment-after-isotope-runs-scarce"},{"label":"DOE Isotope R&D and Production overview","url":"https://www.energy.gov/science/ip/isotope-rd-and-production-doe-ip"},{"label":"PanTera secures funding to scale actinium-225 production (company announcement, via Synapse)","url":"https://synapse.patsnap.com/article/pantera-secures-E282AC134m-to-boost-actinium-225-production"}],"tags":["alpha emitter","supply chain","actinium-225"],"related":["idea-reg-legacy-radium-recovery-ac225","idea-reg-alpha-emitter-portfolio","idea-reg-ac225-accelerator-pharmacopoeia","idea-reg-isotope-supply-observatory","b-rlt-trial-capacity","b-manufacturing-cell-therapy","ac-225"],"indications":[],"sections":[],"technologies":["actinium-225-supply","targeted-alpha-therapy","cyclotron-isotope-production","therapy-isotope-supply-chain"],"targets":[],"drugs":["ac225-psma","ryz101"],"companies":["rayzebio","bms","actinium-pharmaceuticals","terrapower-isotopes","orano-med","northstar-medical-radioisotopes","bayer"],"institutions":[],"pathways":[],"terms":[],"trials":["action-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"regulation-manufacturing","severity":"critical","metrics":[{"label":"Legacy thorium-229 generator supply, worldwide","value":"~63 GBq (1.7 Ci) per year across 4 sites","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12468084/"},{"label":"Patients that legacy supply can treat per year","value":"100–200 globally","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12468084/"},{"label":"Estimated annual demand from research and clinical trials alone","value":"~185 GBq (5 Ci)/year","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12468084/"},{"label":"RayzeBio (BMS) paused new enrolment in phase 3 ACTION-1 trial","value":"June 2024, cited as due to actinium-225 shortage","url":"https://www.fiercepharma.com/pharma/bms-and-rayzebio-halt-radiotherapy-trial-enrollment-after-isotope-runs-scarce"}],"causes":["Only four sites worldwide hold a usable thorium-229 stockpile, and one (Russia's IPPE) does not supply regularly.","Direct accelerator production of actinium-225 from radium-226 or thorium-232 is technically demanding and has not yet been demonstrated at industrial scale outside pilot facilities.","Radium-226 feedstock itself is scarce and its supply chain (legacy sealed sources, mining by-product) is not yet organised for pharmaceutical use.","Alpha-emitter production and purification require heavier shielding and faster processing than beta emitters because of short-lived, highly active daughter nuclides."],"currentEfforts":["US DOE Isotope Program tri-laboratory accelerator effort (Brookhaven National Laboratory, Los Alamos National Laboratory, Oak Ridge National Laboratory) producing actinium-225 by proton irradiation.","Commercial accelerator-route entrants (e.g. cyclotron irradiation of radium-226, announced by CNL/ITM-linked ventures from October 2024) aiming for GMP-grade supply.","Bayer's supply agreement with an accelerator-route producer to secure actinium-225 for its own clinical programmes from H2 2024.","BMS/RayzeBio advancing on-site accelerator production to de-risk its own trial supply after the ACTION-1 pause."],"successLooksLike":"Multiple independent, non-Th-229-dependent producers scaling to tens of curies a year of GMP-grade actinium-225, enough that a single supplier problem no longer stops a phase 3 trial.","route":"/bottlenecks/b-ac225-supply/"}
{"id":"b-mo99-supply","kind":"bottleneck","name":"Molybdenum-99 supply","aka":[],"tldr":"Most of the world's everyday nuclear medicine scans depend on a radioactive metal, molybdenum-99, made in a handful of ageing research reactors. When one of them breaks down, hospitals thousands of miles away run short of scans within days because the material decays so fast it cannot be stockpiled.","summary":"Technetium-99m, used in roughly two-thirds of all nuclear medicine procedures worldwide, is generated on-site from its parent, molybdenum-99 (Mo-99, half-life 66 hours). Around 95% of global Mo-99 supply comes from a small set of research reactors, several of them from the 1950s-60s: BR2 (Belgium, commissioned 1961), SAFARI-1 (South Africa, 1965), LVR-15 (Czechia, 1957), MARIA (Poland, 1974), HFR (Netherlands, 1961) and OPAL (Australia, 2006, the newest of the group). These reactors were not built for continuous isotope production, so unplanned outages are common; the HFR was shut down in October 2024 for an unscheduled structural repair, compounding scheduled maintenance elsewhere and tightening Tc-99m availability in Europe and North America.\n\nBecause Mo-99 and its daughter Tc-99m decay too quickly to stockpile, the whole chain -- irradiation, chemical processing, generator manufacture, air freight, and hospital elution -- has to run on a near-continuous, just-in-time schedule with almost no buffer. The United States, which consumes more than half of global Tc-99m demand, has historically produced none of the Mo-99 it uses, importing all of it from these ageing overseas reactors.\n\nThe response has been diversification rather than a single fix: new LEU-target and cyclotron-based domestic production efforts in the US and Canada, a CMS reimbursement add-on to reward non-highly-enriched-uranium production, and a slow build-out of newer reactors and accelerator routes to replace the 1960s fleet as it eventually retires.","asOf":"2026-09-22","links":[{"label":"OECD-NEA: Current trends in the supply and utilisation of medical radioisotopes (Oct 2025)","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"McGuireWoods: Radiopharmaceutical industry update, CY2025 HOPPS rule and Mo-99 add-on payment","url":"https://www.mcguirewoods.com/client-resources/alerts/2025/4/radiopharmaceutical-industry-update-q4-q1-2024-2025/"},{"label":"INMM PATRAM 2010: Transport of radiopharmaceuticals, cradle to the patient","url":"https://resources.inmm.org/system/files/patram_proceedings/2010/233_Paper_TRANSPORT-OF-RADIOPHARMACEUTICALS,-CRADLE-TO-THE-P.pdf"}],"tags":["supply chain","molybdenum-99","technetium-99m","reactor infrastructure"],"related":["idea-reg-medical-isotope-reactor-reserve","idea-reg-isotope-supply-observatory","b-cold-chain-logistics","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":["northstar-medical-radioisotopes","shine-technologies","curium","ntp-radioisotopes","ire","ansto","nordion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"regulation-manufacturing","severity":"major","metrics":[{"label":"Share of global Mo-99 supply from six ageing research reactors","value":"~95%","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"Oldest Mo-99-producing reactor still in service (LVR-15, Czechia)","value":"commissioned 1957","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"HFR (Netherlands) unplanned shutdown","value":"October 2024, structural repair","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"CMS add-on payment for Tc-99m from domestically produced (non-HEU) Mo-99","value":"$10 per dose, effective 1 January 2026","url":"https://www.mcguirewoods.com/client-resources/alerts/2025/4/radiopharmaceutical-industry-update-q4-q1-2024-2025/"},{"label":"Activity lost to a one-day transport delay of Mo-99 (66-hour half-life)","value":"~22%","url":"https://resources.inmm.org/system/files/patram_proceedings/2010/233_Paper_TRANSPORT-OF-RADIOPHARMACEUTICALS,-CRADLE-TO-THE-P.pdf"}],"causes":["Global Mo-99 production is concentrated in a small number of research reactors originally built for other purposes and now decades past their design life.","The isotope's 66-hour half-life means there is no meaningful stockpile; any outage propagates into a shortage within days.","Historic reliance on highly enriched uranium (HEU) targets created conversion costs and regulatory complexity when moving to low-enriched uranium (LEU).","Low economic return on Mo-99 production relative to its public-health importance has discouraged reactor operators from investing in dedicated new capacity."],"currentEfforts":["NorthStar Medical Radioisotopes and SHINE Technologies scaling non-uranium (accelerator- and fusion-based) domestic US Mo-99 production.","Canada's Darlington Nuclear Generating Station (CANDU) beginning Mo-99, Lu-177 and Y-90 production runs from 2025.","CMS's CY2025/2026 rule adding a $10-per-dose payment for Tc-99m derived from domestically produced, non-HEU Mo-99.","Private US test reactors (e.g. Oklo's Groves Isotope Test Reactor, first criticality August 2026) aiming to prove domestic medical-isotope production pathways."],"successLooksLike":"Mo-99 production diversified across enough LEU and non-reactor routes, in enough countries, that a single reactor's unplanned outage no longer causes a multi-country Tc-99m shortage.","route":"/bottlenecks/b-mo99-supply/"}
{"id":"b-enriched-target-material","kind":"bottleneck","name":"Enriched target material for therapeutic isotopes","aka":[],"tldr":"Making the pure form of lutetium-177 used in cancer drugs like Pluvicto requires starting from a rare, heavily purified metal called ytterbium-176. Almost all of the world's supply of that starting material has come from one country, which is a risky place for the whole medicine to depend on.","summary":"No-carrier-added lutetium-177 (177Lu), the form used in Pluvicto and Lutathera, is made by neutron-irradiating a target of ytterbium enriched to above 96-99% in the stable isotope ytterbium-176, then chemically separating the trace lutetium-177 produced. Only about one in 5,000 atoms in the irradiated target ends up as lutetium-177, and producing the same activity by this route needs roughly a thousand times more enriched starting material than the alternative (but lower-purity) carrier-added route using enriched lutetium-176. There is no accelerator-based alternative: no-carrier-added Lu-177 can only be made by neutron irradiation of Yb-176.\n\nThe enrichment step itself -- separating Yb-176 from the other six stable ytterbium isotopes -- has historically been dominated by Russian electromagnetic separators (calutrons), described by the EU's Economic and Social Committee as 100% European dependence on Russia for this specific material. The US Department of Energy's Oak Ridge National Laboratory restarted its own electromagnetic separation in the early 2020s but as of 2022 could only offer 'research quantities' not available for commercial resale, and Western capacity has generally atrophied because the customer base for any single enriched isotope is small and capital costs are high.\n\nThe same underlying problem -- a handful of highly specialised, low-throughput separation facilities feeding a fast-growing radioligand therapy market -- applies to other enriched targets in the pipeline (enriched molybdenum-100 for cyclotron-based Mo-99/Tc-99m, enriched gadolinium for astatine-211 routes), making enriched stable-isotope supply a structural constraint on the whole field, not just on lutetium-177.","asOf":"2026-09-22","links":[{"label":"Challenges and future options for the production of lutetium-177 (EJNMMI, 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8241800/"},{"label":"One country's isotope, everyone's cancer drug (Problem Genome brief on Yb-176 dependence)","url":"https://www.problemgenome.com/briefs/health-yb176-enriched-isotope-single-country-supply"},{"label":"DOE Isotope R&D and Production, FY2025 budget request (stable isotope enrichment priorities)","url":"https://www.energy.gov/sites/default/files/2024-03/FY2025-PresidentsRequest-IRP.pdf"}],"tags":["supply chain","ytterbium-176","lutetium-177","enrichment"],"related":["idea-reg-yb176-enrichment-capacity","b-mo99-supply","b-ac225-supply","tc-99m","mo-99","lu-177","at-211"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain","research-reactor-isotope-production","lu177-radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera","itm-11"],"companies":["novartis","itm","ntp-radioisotopes","curium"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"regulation-manufacturing","severity":"major","metrics":[{"label":"Fraction of irradiated ytterbium-176 target atoms converted to lutetium-177","value":"~1 in 5,000","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8241800/"},{"label":"Extra enriched target material needed for the no-carrier-added (Yb-176) route vs the carrier-added (Lu-176) route, for equivalent activity","value":"~1,000-fold more","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8241800/"},{"label":"EU dependence on Russia for enriched ytterbium-176 supply","value":"100% (EU Economic and Social Committee statement)","url":"https://www.problemgenome.com/briefs/health-yb176-enriched-isotope-single-country-supply"}],"causes":["There is no feasible accelerator- or proton-based production route for lutetium-177: only neutron irradiation works, which locks the process to a small number of high-flux research reactors and to whichever enriched target is available to them.","Enrichment of ytterbium-176 requires electromagnetic separators (calutrons), gas centrifuges, or laser separation -- all capital-intensive, low-throughput technologies with very few operators worldwide.","The customer base for any single enriched stable isotope is small, so for decades it was cheaper to buy Russian material than to build competing Western capacity, and that Western capacity atrophied.","Chemical recovery and recycling of the expensive enriched ytterbium target after irradiation is technically demanding, so yields and reuse rates limit how far existing enriched stock can be stretched."],"currentEfforts":["US DOE Isotope Program restarting electromagnetic isotope separation and building the Stable Isotope Production Facility at Oak Ridge National Laboratory, initially for other isotopes (e.g. xenon-129) with stable-isotope enrichment as a stated strategic priority including ytterbium-176.","EU SAMIRA action plan and Euratom research calls specifically funding alternative, non-Russian ytterbium-176 production routes.","Radiopharmaceutical manufacturers (Novartis, ITM, others) reported to be pursuing multiple, geographically diversified Yb-176 supply agreements to reduce single-country exposure."],"successLooksLike":"At least two commercially viable, non-Russian sources of pharmaceutical-grade enriched ytterbium-176 (or an alternative no-carrier-added Lu-177 production route), so that lutetium-177 supply is not exposed to a single country's export policy.","route":"/bottlenecks/b-enriched-target-material/"}
{"id":"b-hot-lab-capacity","kind":"bottleneck","name":"Hot lab and shielded treatment room capacity","aka":[],"tldr":"Even where the radioactive medicine itself is available, giving it to a patient needs a specially shielded room, lead-lined equipment, and a toilet that can hold radioactive waste safely. Most hospitals only have one or two of these set up, which limits how many patients they can treat each week.","summary":"Administering a radioligand therapy such as 177Lu-PSMA-617 or 177Lu-DOTATATE requires a licensed 'hot lab': shielded space for receiving and dispensing the dose, a dose calibrator, syringe shields and pumps, and a decay-storage area for waste and used consumables. A 2021 German capacity analysis estimated the country's nationwide nuclear-medicine therapy bed capacity at around 234,000 treatment-days a year with a reserve of only about 19,000 bed-days (roughly 63 beds), concluding that Lu-177-PSMA therapy could reach that capacity limit in some federal states even before newer indications or additional radiopharmaceuticals are added.\n\nBuilding a hot lab is expensive and slow: the Netherlands' national innovation ecosystem review describes hot labs costing in the order of millions of euros and taking multiple years to set up, and notes that because they are often designed around a specific radiopharmaceutical, they may not flex to accommodate other products. Some centres, particularly urology clinics starting smaller programmes, have instead converted an existing procedure room into a part-time hot lab (used on designated days each month) with reinforced cabinetry, a second 'hot trash' bin, and a syringe pump and shield -- a lower-cost model that suits a modest caseload but does not scale to high volume.\n\nManufacturers have partly addressed the manufacturing side of this bottleneck (Novartis added a fourth global production site after Pluvicto's 2022-23 shortage and reports network capacity exceeding 250,000 doses a year), but the administration side -- shielded rooms, decay-tank capacity, and trained staff at the point of care -- has not scaled at the same pace, so treatment slots rather than drug supply are increasingly the limiting step at busy centres.","asOf":"2026-09-22","links":[{"label":"PSMA radioligand therapy could pose infrastructural challenges for nuclear medicine (German bed-capacity calculation)","url":"https://pubmed.ncbi.nlm.nih.gov/33530110/"},{"label":"How one urology clinic set up a hot lab for a radioligand therapy programme (UroToday)","url":"https://www.urotoday.com/video-lectures/practical-aspects-of-operationalizing-lutetium-177-177lu-psma-617-in-the-urology-clinic/video/3623-how-one-urology-clinic-successfully-sets-up-a-hot-lab-for-radioligand-therapy-program-william-oresick.html"},{"label":"The Dutch innovation ecosystem for nuclear medicine (hot lab cost and scarcity)","url":"https://nvng.nl/wp-content/uploads/FAST-rapportage-medische-isotopen_def.pdf"},{"label":"Radiopharmaceutical supply chain under pressure: can infrastructure keep up with demand?","url":"https://www.scienceandmedicinegroup.com/resource/radiopharmaceutical-supply-chain-under-pressure-can-infrastructure-keep-up-with-demand/"}],"tags":["infrastructure","hot lab","capacity"],"related":["b-site-readiness-referral","b-nuclear-medicine-workforce","b-radioactive-waste-regulation","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","radiopharmacy-network","nuclear-medicine-hardware","lu177-radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":["novartis","itm"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"access-delivery","severity":"major","metrics":[{"label":"German nationwide nuclear-medicine therapy bed reserve for Lu-177-PSMA-RLT","value":"~19,000 of 234,000 bed-days/year (≈63 beds)","url":"https://pubmed.ncbi.nlm.nih.gov/33530110/"},{"label":"Novartis global radioligand therapy manufacturing network capacity target","value":">250,000 doses/year (company figure)","url":"https://www.scienceandmedicinegroup.com/resource/radiopharmaceutical-supply-chain-under-pressure-can-infrastructure-keep-up-with-demand/"}],"causes":["Hot labs cost in the order of millions of euros and take years to build, and are often engineered around one specific radiopharmaceutical rather than being flexible to new agents.","Shielded patient rooms and dedicated 'hot' toilets with radioactive-waste decay tanks are a fixed physical constraint at most hospitals, typically only two or three per site.","Nuclear-medicine bed and hot-lab capacity was planned around historic diagnostic and legacy-therapy caseloads, not the scale of demand created by PSMA- and SSTR-directed radioligand therapy.","Manufacturing capacity for the drug product itself has been scaled up faster than administration-site infrastructure, shifting the binding constraint downstream to the point of care."],"currentEfforts":["Novartis operating four global manufacturing sites for Pluvicto/Lutathera after the 2023 shortage, reporting combined capacity above 250,000 doses/year.","Community urology and oncology clinics converting existing procedure rooms into part-time hot labs (reinforced cabinetry, dedicated syringe shields/pumps, extra decay storage) as a lower-capital entry model.","Hospitals building dedicated 'theranostics wings' with multiple shielded rooms as radioligand therapy caseloads grow."],"successLooksLike":"Shielded room, decay-tank, and trained-staff capacity at treatment sites scale ahead of dose-manufacturing capacity, so an available dose is never wasted because there is nowhere and no one to give it to.","route":"/bottlenecks/b-hot-lab-capacity/"}
{"id":"b-authorized-user-shortage","kind":"bottleneck","name":"Authorized user shortage for radionuclide therapy","aka":[],"tldr":"In the US, only specially trained doctors are legally allowed to give radioactive cancer treatments. Whether there are enough of these doctors to keep up with demand is genuinely disputed: regulators and physician groups have looked at the numbers and reached different conclusions.","summary":"Under US NRC rule 10 CFR 35.390, only a physician who has completed the required training and experience -- either full nuclear medicine/radiation oncology board certification, or an alternate pathway of about 700 hours (roughly four months) of structured training -- can become an 'Authorized User' (AU) and administer radionuclide therapies requiring a written directive. Since 2017-2018 the NRC's Advisory Committee on the Medical Uses of Isotopes (ACMUI) has repeatedly examined whether a future AU shortage will bottleneck access to radioligand therapy, prompted by the approval of 177Lu-DOTATATE and the shrinking pipeline of US-trained nuclear medicine physicians.\n\nThe evidence is contested. A 2019 JNM editorial estimated the existing board-certified US nuclear medicine physician workforce at around 1,200, with 50-60 new ABNM diplomates entering annually, and projected that meeting demand for 150,000-200,000 radionuclide therapy cycles a year (roughly 50,000 patients at four cycles each) would need about 150 dedicated theranostic centres -- a number the authors argued the existing and incoming workforce could support, so long as radiologists and radiation oncologists trained under the alternate pathway are counted. The NRC's own ACMUI subcommittee concluded in 2018-2019 that there was 'no objective data to confirm an authorized user shortage' and did not recommend creating a lower-training limited-scope AU pathway.\n\nWhatever the physician-supply numbers show nationally, the practical effect for patients is the same: AU status is concentrated in nuclear medicine, radiology and radiation oncology, not in the medical oncology clinics that manage most prostate cancer and neuroendocrine tumour patients, so referral to a licensed, AU-staffed centre remains an extra step in every patient's pathway.","asOf":"2026-09-22","links":[{"label":"JNM editorial: Delivering radionuclide therapies requires extensive training and competence","url":"https://jnm.snmjournals.org/content/60/1/1"},{"label":"NRC Advisory Committee on the Medical Uses of Isotopes, transcript on AU shortage evidence","url":"https://www.nrc.gov/docs/ML1907/ML19077A112.pdf"},{"label":"NRC: Authorized Individuals (10 CFR Part 35 training requirements)","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/auth-individuals"},{"label":"SNMMI Theranostics Stakeholders Summit white paper (2025)","url":"https://snmmi.org/common/Uploaded%20files/News/Theranostics_Stakeholders_Summit_White_Paper_FINAL_6-2025.pdf"}],"tags":["workforce","regulation","authorized user"],"related":["b-nuclear-medicine-workforce","b-site-readiness-referral","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy","prrt","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":["snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"people-culture","severity":"moderate","metrics":[{"label":"Training hours required for the 10 CFR 35.390 alternate Authorized User pathway","value":"700 hours (~4 months)","url":"https://jnm.snmjournals.org/content/60/1/1"},{"label":"Estimated US board-certified nuclear medicine physician workforce (2019)","value":"~1,200, plus 50–60 new ABNM diplomates/year","url":"https://jnm.snmjournals.org/content/60/1/1"},{"label":"Estimated dedicated theranostic centres needed for projected US radionuclide-therapy demand","value":"~150 centres for 150,000–200,000 cycles/year","url":"https://jnm.snmjournals.org/content/60/1/1"},{"label":"NRC ACMUI subcommittee finding on AU shortage evidence","value":"\"No objective data to confirm an authorized user shortage\" (2018–19)","url":"https://www.nrc.gov/docs/ML1907/ML19077A112.pdf"}],"causes":["Authorized User status requires either full nuclear medicine/radiation oncology board certification or a separate, lengthy alternate training pathway that most medical oncologists never complete.","The physicians who see most prostate cancer and neuroendocrine tumour patients (medical oncologists, urologists) are usually not the physicians licensed to administer the radioactive therapy itself.","Whether a genuine national AU shortage exists is disputed between professional societies and NRC advisory findings, which has slowed any policy resolution either way."],"currentEfforts":["NRC ongoing Federal Register outreach and stakeholder consultation (since 2018) on whether to create a limited-scope AU pathway specifically for radiopharmaceutical therapy.","SNMMI's 2025 Theranostics Stakeholders Summit naming workforce education and training as one of four priority focus areas for the field.","University of Alabama at Birmingham / SNMMI Nuclear Medicine Therapy Intensive, launched 2024, as a dedicated short-course training route for physicians and staff entering radioligand therapy."],"successLooksLike":"A data-driven, agreed assessment of AU supply versus projected radioligand-therapy demand, and, if a genuine gap is confirmed, a validated limited-scope training pathway that expands capacity without compromising radiation safety.","route":"/bottlenecks/b-authorized-user-shortage/"}
{"id":"b-nuclear-medicine-workforce","kind":"bottleneck","name":"Nuclear medicine technologist and physicist workforce","aka":[],"tldr":"Radioactive cancer treatments need specially trained technologists and physicists to prepare and check every dose, and there simply are not enough of them. Hospitals in Europe, the US and Canada are all reporting job vacancies that stay open for months.","summary":"A 2024 EANM cross-sectional survey of the European nuclear medicine workforce (239 respondents, 31 countries) found that 80.2% of departments reported at least one open vacancy, with technologists/radiographers hit hardest (61.6% vacancy rate) followed by physicians (57.1%); more than half of all open positions (57.7%) had remained unfilled for six months or longer. In the United States, a 2026 SNMMI-TS/NMTCB salary and workforce study surveyed 26,336 nuclear medicine technologists and received 2,271 responses, finding median hourly pay had risen 15% (to $51.28) since 2022 -- itself a sign of a tight labour market pushing wages up to attract staff.\n\nThe pipeline problem is structural, not just cyclical: a US analysis found the certified nuclear medicine technologist workforce shrank by about 1,438 people (6%) between 2012 and 2022 as training programmes closed and experienced staff left the field, and a follow-up regional survey found roughly a quarter of working technologists plan to retire or leave direct patient care within 5-10 years. SNMMI's own 2025 Theranostics Stakeholders Summit survey found 70.5% of responding institutions had current hiring vacancies in nuclear medicine or theranostics.\n\nThis workforce gap sits underneath, and partly explains, several of the field's other access problems: without enough technologists to run cameras and generators, and physicists to support dosimetry and quality assurance, expanding hot-lab and treatment-room capacity does not translate into more patients treated.","asOf":"2026-09-22","links":[{"label":"EANM nuclear medicine workforce survey (European Journal of Nuclear Medicine, 2024 data)","url":"https://boa.unimib.it/retrieve/2b572834-6cd0-4a4d-af21-27e8aa4987a1/Van%20den%20Wyngaert%20et%20al-2026-The%20EANM%20Journal-VoR.pdf"},{"label":"SNMMI-TS and NMTCB 2026 Salary and Workforce Study","url":"https://snmmi.org/common/Uploaded%20files/Web/Research-Publications/2026%20Salary%20and%20Workforce%20Study.pdf"},{"label":"Future challenges and occupational prospects of nuclear medicine technologists (JNM abstract)","url":"https://jnm.snmjournals.org/content/64/supplement_1/TS19"},{"label":"SNMMI Theranostics Stakeholders Summit white paper (2025), staffing survey","url":"https://snmmi.org/common/Uploaded%20files/News/Theranostics_Stakeholders_Summit_White_Paper_FINAL_6-2025.pdf"}],"tags":["workforce","technologists","training"],"related":["b-authorized-user-shortage","b-hot-lab-capacity"],"indications":[],"sections":[],"technologies":["radiopharmacy-network","radioligand-dosimetry","nuclear-medicine-hardware"],"targets":[],"drugs":[],"companies":[],"institutions":["snmmi","eanm"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"people-culture","severity":"major","metrics":[{"label":"European nuclear medicine departments reporting an open vacancy (EANM 2024 survey)","value":"80.2%","url":"https://boa.unimib.it/retrieve/2b572834-6cd0-4a4d-af21-27e8aa4987a1/Van%20den%20Wyngaert%20et%20al-2026-The%20EANM%20Journal-VoR.pdf"},{"label":"Technologist/radiographer vacancy rate in Europe (EANM 2024 survey)","value":"61.6% of departments","url":"https://boa.unimib.it/retrieve/2b572834-6cd0-4a4d-af21-27e8aa4987a1/Van%20den%20Wyngaert%20et%20al-2026-The%20EANM%20Journal-VoR.pdf"},{"label":"European vacancies unfilled for 6 months or longer","value":"57.7% of open positions","url":"https://boa.unimib.it/retrieve/2b572834-6cd0-4a4d-af21-27e8aa4987a1/Van%20den%20Wyngaert%20et%20al-2026-The%20EANM%20Journal-VoR.pdf"},{"label":"US nuclear medicine technologist workforce change, 2012–2022","value":"-1,438 (-6%)","url":"https://jnm.snmjournals.org/content/64/supplement_1/TS19"},{"label":"US NMTs surveyed who plan to retire or leave direct patient care within 5–10 years","value":"~26% (regional survey)","url":"https://jnm.snmjournals.org/content/64/supplement_1/TS19"},{"label":"SNMMI 2026 median NMT hourly pay, and change since 2022","value":"$51.28, up 15% from $44.65","url":"https://snmmi.org/common/Uploaded%20files/Web/Research-Publications/2026%20Salary%20and%20Workforce%20Study.pdf"},{"label":"US institutions reporting current hiring vacancies in nuclear medicine/theranostics (SNMMI Summit survey)","value":"70.5%","url":"https://snmmi.org/common/Uploaded%20files/News/Theranostics_Stakeholders_Summit_White_Paper_FINAL_6-2025.pdf"}],"causes":["Accredited nuclear medicine technologist training programmes have closed in several countries, shrinking the pipeline just as radioligand therapy caseloads are growing.","A wave of experienced technologists and physicists is approaching retirement at the same time demand is rising.","COVID-era attrition reduced the healthcare workforce broadly, and nuclear medicine has not recovered as quickly as some other specialties.","Pay and career-pathway visibility have historically lagged other imaging professions, making recruitment harder even where training capacity exists."],"currentEfforts":["University of Alabama at Birmingham / SNMMI Nuclear Medicine Therapy Intensive (launched 2024) providing dedicated short-course training for the theranostics workforce.","EANM educational outreach, career pathway resources and professional development initiatives flagged in its 2024 workforce survey.","Canadian Association of Nuclear Medicine's 2025 National White Paper on the technologist shortage, informing provincial training-capacity planning.","Rising technologist pay (SNMMI-TS/NMTCB 2026 study) as institutions compete for a limited pool of qualified staff."],"successLooksLike":"Vacancy rates for nuclear medicine technologists and physicists fall towards the low single digits, and training-programme capacity grows in step with radioligand therapy caseload growth rather than lagging behind it.","route":"/bottlenecks/b-nuclear-medicine-workforce/"}
{"id":"b-dosimetry-standardisation","kind":"bottleneck","name":"Dosimetry standardisation for radioligand therapy","aka":[],"tldr":"Doctors give almost every patient the same fixed amount of radioactive drug, rather than measuring how much radiation each person's tumour and organs actually absorb and adjusting the dose. Personalising the dose might work better for some patients, but nobody has yet proven it clearly enough for it to become the standard of care.","summary":"177Lu-PSMA-617 (Pluvicto) is approved and almost always given at a fixed activity of 7.4 GBq every six weeks; the joint 2023 EANM/SNMMI procedure guideline confirms that patient-specific dosimetry is not mandatory for in-label use. Yet academic dosimetry studies show wide inter-patient variation: EANM Dosimetry Committee analyses report that the number of PRRT cycles needed to reach a preset kidney absorbed-dose limit ranges from 2 to 10 across patients, and the total activity required to hit that limit varies by a factor of roughly 1.5 for somatostatin-receptor therapy and by a factor of 3 for PSMA therapy.\n\nThe unresolved question is whether measuring and personalising that dose actually improves outcomes enough to justify the extra imaging burden. In its January 2025 reply to an EMA concept paper on clinical evaluation of therapeutic radiopharmaceuticals, EANM stated plainly that 'divergent opinion persists... the lack of sufficiently robust evidence demonstrating that personalizing administered activities based on dosimetry provides tangible benefits' means EANM does not hold a definitive position recommending dosimetry-guided over fixed-activity dosing. Methods themselves are only partly harmonised: the EANM Dosimetry Committee's 2022 recommendations for 177Lu-SSTR/PSMA dosimetry, and MIRD Pamphlet No. 26 for quantitative 177Lu SPECT, describe standard operating procedures, but implementation still varies by centre in imaging timepoints, segmentation method and software.\n\nAlpha emitters add a further layer of difficulty: EANM's same 2025 submission flags that actinium-225's limited imaging potential on current nuclear-medicine cameras means image-based dosimetry approaches developed for beta emitters do not simply transfer across, and new strategies or technology are still needed.","asOf":"2026-09-22","links":[{"label":"EANM Dosimetry Committee recommendations for 177Lu-labelled SSTR/PSMA ligands (2022)","url":"https://link.springer.com/article/10.1007/s00259-022-05727-7"},{"label":"Joint EANM/SNMMI procedure guideline for 177Lu-PSMA-RLT (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"},{"label":"EANM reply to EMA consultation on clinical evaluation of therapeutic radiopharmaceuticals (Jan 2025)","url":"https://eanm.org/wp-content/uploads/2025/02/EANM-Reply-to-the-public-consultation-on-the-European-Medicines-Agency-Concept-paper-on-clinical-evaluation-of-therapeutic-radiopharmaceuticals-in-oncology.pdf"}],"tags":["dosimetry","standardisation","guideline"],"related":["idea-net-dosimetry-prrt","idea-total-body-pet-dosimetry","b-dose-optimisation","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","quantitative-imaging-biomarkers","prrt"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":["eanm","snmmi","ema"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"data-knowledge","severity":"moderate","metrics":[{"label":"Number of PRRT cycles needed to reach a preset kidney dose limit, across patients","value":"range 2–10 cycles","url":"https://link.springer.com/article/10.1007/s00259-022-05727-7"},{"label":"Variation in total activity needed to reach a preset absorbed-dose limit","value":"~1.5-fold (SSTR therapy), ~3-fold (PSMA therapy)","url":"https://link.springer.com/article/10.1007/s00259-022-05727-7"},{"label":"177Lu-PSMA-617 approved regimen: fixed activity per cycle","value":"7.4 GBq (200 mCi) every 6 weeks (±1 week), dosimetry not mandatory in-label","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"}],"causes":["No large randomised trial has yet shown that dosimetry-guided individualised dosing improves survival or reduces toxicity compared with fixed-activity dosing.","Dosimetry protocols (imaging timepoints, organ/tumour segmentation, software) are not fully harmonised across centres, so results are not always directly comparable.","Multiple SPECT/CT imaging sessions over days add patient burden and resource use that many centres cannot absorb for every patient.","Alpha emitters such as actinium-225 are difficult to image directly with current nuclear medicine cameras, so beta-emitter dosimetry methods do not transfer straightforwardly."],"currentEfforts":["EANM Dosimetry Committee recommendations (2022) for harmonised dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands.","Joint EANM/MIRD Pamphlet No. 26 on quantitative 177Lu SPECT methodology for dosimetry.","EANM's proposal, in its 2025 EMA consultation reply, for a unified pan-European database to pool dosimetric data across centres and generate the evidence base still missing.","EANM guidance document specifically for dosimetry in first-in-human and early-phase clinical trials of new radioligands."],"successLooksLike":"A trial-validated, low-burden dosimetry protocol shown to improve outcomes or reduce toxicity versus fixed dosing, harmonised across centres and reimbursed as standard practice where it adds value.","route":"/bottlenecks/b-dosimetry-standardisation/"}
{"id":"b-reimbursement-coding","kind":"bottleneck","name":"Reimbursement and coding for radiopharmaceuticals","aka":[],"tldr":"In the US, insurance pays extra for a new radioactive scan for a couple of years, then that extra payment can suddenly stop, even though the drug still costs the same to make. That cliff has already made at least one scan much harder for patients to get.","summary":"US Medicare has historically packaged diagnostic radiopharmaceuticals into the payment for the imaging test itself, treating them as a 'supply' rather than reimbursing their actual cost. New diagnostic radiopharmaceuticals typically get two to three years of transitional 'pass-through' status, during which their cost is separately and fully reimbursed; once pass-through expires, additional payment can drop to zero, which the American College of Radiology cites as the reason amyloid PET imaging has had persistently limited availability.\n\nAfter years of lobbying by SNMMI, ACR and others, CMS's CY2025 Hospital Outpatient Prospective Payment System (HOPPS) final rule, released 1 November 2024 and effective 1 January 2025, created a new middle tier: any diagnostic radiopharmaceutical without pass-through status, whose per-day cost exceeds a $630 threshold (set at twice the average $314 CMS assumed was already bundled into existing payments), now receives ongoing separate payment based on Mean Unit Cost (MUC) derived from hospital claims data. Twenty-six products qualified for 2025, more than half of them PET tracers; the threshold is indexed to the Producer Price Index for Pharmaceuticals from 2026 onward.\n\nA parallel change took effect for the isotope supply chain itself: from 1 January 2026, CMS pays a $10-per-dose add-on for technetium-99m derived from domestically produced (non-highly-enriched-uranium) molybdenum-99, intended to reward and de-risk the US reshoring effort described under the Mo-99 supply bottleneck. Therapeutic radiopharmaceuticals remain reimbursed at ASP+6% where average sales price data exists, but manufacturers are not mandated to report ASP, so many still fall back to the same claims-based MUC methodology CMS uses for diagnostics.","asOf":"2026-09-22","links":[{"label":"SNMMI FAQ on CMS CY2025 HOPPS diagnostic radiopharmaceutical payment reform","url":"https://snmmi.org/Web/Web/News/Articles/FAQs-on-the-Centers-for-Medicare---Medicaid-Services--CMS--Major-Payment-Policy-Reform-for-Diagnosti.aspx"},{"label":"ACR Bulletin: Changes to reimbursement for high-cost radiopharmaceuticals","url":"https://www.acr.org/Clinical-Resources/Publications-and-Research/ACR-Bulletin/Changes-to-Reimbursement-for-High-Cost-Radiopharmaceuticals"},{"label":"McGuireWoods: Radiopharmaceutical industry update, CY2025 HOPPS rule detail","url":"https://www.mcguirewoods.com/client-resources/alerts/2025/4/radiopharmaceutical-industry-update-q4-q1-2024-2025/"},{"label":"ASTRO summary of the 2025 HOPPS final rule (radiopharmaceutical payment policy)","url":"https://www.astro.org/getmedia/8ac4db0c-cd58-42bd-b693-7caa40928919/2025HOPPSFinalRuleSummary.pdf"}],"tags":["reimbursement","CMS","coding","access"],"related":["b-site-readiness-referral","b-mo99-supply","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":["pet-tracer-manufacturing","radiopharmacy-network"],"targets":[],"drugs":["pylarify","illuccix","locametz","pluvicto","lutathera"],"companies":["novartis","telix","lantheus"],"institutions":["snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"funding-incentives","severity":"moderate","metrics":[{"label":"CY2025 HOPPS separate-payment threshold for diagnostic radiopharmaceuticals","value":"$630 per day (2x the $314 CMS assumed was already packaged)","url":"https://snmmi.org/Web/Web/News/Articles/FAQs-on-the-Centers-for-Medicare---Medicaid-Services--CMS--Major-Payment-Policy-Reform-for-Diagnosti.aspx"},{"label":"Diagnostic radiopharmaceuticals qualifying for separate payment in 2025","value":"26 products, >half PET tracers","url":"https://www.acr.org/Clinical-Resources/Publications-and-Research/ACR-Bulletin/Changes-to-Reimbursement-for-High-Cost-Radiopharmaceuticals"},{"label":"New Mo-99 domestic-sourcing add-on payment, effective 1 January 2026","value":"$10 per dose","url":"https://www.mcguirewoods.com/client-resources/alerts/2025/4/radiopharmaceutical-industry-update-q4-q1-2024-2025/"},{"label":"Typical pass-through period before reimbursement can drop to zero","value":"2–3 years","url":"https://www.acr.org/Clinical-Resources/Publications-and-Research/ACR-Bulletin/Changes-to-Reimbursement-for-High-Cost-Radiopharmaceuticals"}],"causes":["Diagnostic radiopharmaceuticals were historically bundled into HOPPS payment for the imaging test as a 'supply', which undervalued high-cost tracers relative to their actual acquisition cost.","Transitional pass-through payment periods expire after 2–3 years, creating a reimbursement cliff exactly when a product is scaling into routine use.","Manufacturers are not required to report average sales price (ASP) data, so CMS has had to rely on claims-derived Mean Unit Cost as a proxy, which lags real-world pricing.","Reimbursement policy has historically been set per-product rather than for the radiopharmaceutical drug class as a whole, so each new tracer or therapy faces the same fight from scratch."],"currentEfforts":["SNMMI and ACR multi-year advocacy that led directly to the CY2025 HOPPS separate-payment policy for diagnostic radiopharmaceuticals.","CMS commitment to index the $630 threshold annually to the Producer Price Index for Pharmaceuticals from 2026, rather than leaving it fixed.","CMS's new domestic Mo-99 sourcing add-on payment, aligning reimbursement incentives with the isotope-supply-chain resilience goals described elsewhere in this graph."],"successLooksLike":"Radiopharmaceutical reimbursement that follows the product's real cost continuously from launch through the life of the pass-through period and beyond, so no approved, clinically useful tracer or therapy loses access because of a coding cliff.","route":"/bottlenecks/b-reimbursement-coding/"}
{"id":"b-cold-chain-logistics","kind":"bottleneck","name":"Cold chain and time-critical logistics","aka":[],"tldr":"Radioactive medicines keep losing strength from the moment they are made, so a doctor prescribes a specific amount to arrive at a specific time. If a flight is delayed, an airline refuses the cargo, or customs holds the package for even a few hours, the dose can decay below the amount a patient needs and has to be thrown away.","summary":"Because radioactive decay cannot be paused, every radiopharmaceutical shipment is ordered as an activity calibrated to a specific date and time, with the manufacturer dispensing extra margin so the prescribed activity still holds when the patient is dosed. For the shortest-lived isotopes the arithmetic is unforgiving: molybdenum-99, with a 66-hour half-life, loses about 22% of its activity to a single day's transport delay. A missed delivery window is not simply a late shipment -- the product is unusable and cannot be replaced from any stockpile.\n\nMost radiopharmaceutical shipments travel as Class 7 dangerous goods under IATA and national transport rules, on top of any temperature control (commonly 2-8°C) the specific product needs, and this dual compliance burden restricts which carriers and routes are available. Some major airlines refuse Class 7 cargo outright, individual pilots have refused loads once they see radioactive labelling, and flights that do accept it often cap the total transport index (radiation level) permitted per aircraft. A 2026 survey of six English-speaking Southern African Development Community countries found customs clearance delays of up to a day reported in South Africa, Zambia, Namibia, Tanzania and Mauritius, with reported order-to-delivery lead times ranging from a few days (regional generator shipments) to about a month for products sourced from further afield.\n\nThe IAEA and ICAO have responded with a formal denial-and-delay-of-shipment reporting mechanism and national focal points to track and resolve recurring blockages, and IATA now requires shippers to hold specific Class 7 certification, but the underlying constraint -- a short, physics-set delivery window intersecting with an inconsistent, carrier-by-carrier and country-by-country regulatory patchwork -- has not been resolved.","asOf":"2026-09-22","links":[{"label":"INMM PATRAM 2010: Transport of radiopharmaceuticals, cradle to the patient","url":"https://resources.inmm.org/system/files/patram_proceedings/2010/233_Paper_TRANSPORT-OF-RADIOPHARMACEUTICALS,-CRADLE-TO-THE-P.pdf"},{"label":"Challenges in radiopharmaceutical importation across six SADC countries (2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13002445/"},{"label":"ICAO Assembly working paper on denial and delay of shipment of radioactive material","url":"https://www.icao.int/sites/default/files/Meetings/a42/Documents/WP/wp_439_en.pdf"},{"label":"Radiopharmaceutical supply chain structure (MedRaySintell)","url":"https://medraysintell.com/radiopharmaceutical-supply-chain-structure-7-7/"}],"tags":["logistics","Class 7","cold chain","half-life"],"related":["idea-reg-regional-radiopharmacy-hubs","b-mo99-supply","b-site-readiness-referral","mo-99"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain","radiopharmacy-network","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"access-delivery","severity":"moderate","metrics":[{"label":"Activity lost to a one-day transport delay of molybdenum-99 (66-hour half-life)","value":"~22%","url":"https://resources.inmm.org/system/files/patram_proceedings/2010/233_Paper_TRANSPORT-OF-RADIOPHARMACEUTICALS,-CRADLE-TO-THE-P.pdf"},{"label":"Reported radiopharmaceutical order-to-delivery lead times across surveyed SADC countries","value":"range: a few days to ~1 month","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13002445/"},{"label":"Customs clearance delays reported for radiopharmaceutical imports","value":"up to ~1 day, in multiple surveyed countries","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13002445/"}],"causes":["Radioactive decay is continuous and irreversible, so there is no buffer stock to fall back on if a shipment is delayed anywhere in the chain.","Radiopharmaceuticals must simultaneously meet Class 7 radioactive-material transport rules and, for many products, refrigerated cold-chain requirements, a combination few carriers are equipped or willing to handle.","Some airlines and individual crews decline Class 7 cargo outright, narrowing available routes, and remaining carriers cap how much transport-index (radiation level) cargo they will carry per flight.","Customs procedures for radioactive material are inconsistently applied across countries, and staff at many border posts have limited familiarity with the specific documentation required."],"currentEfforts":["IAEA/ICAO joint denial-and-delay-of-shipment (DoS) reporting framework, with each IAEA member state encouraged to nominate a National Focal Point to resolve recurring blockages.","IATA Class 7 shipper certification requirements intended to standardise documentation and reduce carrier refusals.","Specialised radiopharma logistics providers building dedicated Class 7 lanes and direct routing to minimise transit hours for short-half-life products.","Customs staff education programmes proposed in regional supply-chain studies to reduce clearance delays for time-critical shipments."],"successLooksLike":"Harmonised customs treatment and reliable Class 7 carrier capacity worldwide, so that radioactive decay -- not paperwork, airline policy, or a border delay -- is the only factor limiting how far a dose can travel.","route":"/bottlenecks/b-cold-chain-logistics/"}
{"id":"b-site-readiness-referral","kind":"bottleneck","name":"Site readiness and referral pathway delays","aka":[],"tldr":"Getting a patient from 'this treatment might help you' to actually receiving it can take weeks or months, because the scan, the specialist review and the treatment often happen at different places, and not every hospital is equipped to give the treatment at all.","summary":"Radioligand therapy referral is a multi-step journey: a treating physician suspects eligibility, the patient needs a PSMA- or somatostatin-receptor PET scan (often at a different centre from where the eligibility decision or treatment happens), a multidisciplinary team reviews the scan, and only then is the patient scheduled at a licensed, hot-lab-equipped centre. A 2025 IQVIA Institute study of the mCRPC referral pathway in Germany, France, Italy and China found this took a minimum of about 7 weeks in Germany, 8-9 weeks in France and China, and roughly 11 weeks in Italy, with limited PSMA PET-CT capacity and unclear division of responsibility between urologists, oncologists and nuclear medicine physicians cited as common barriers across all four countries.\n\nA report from Dana-Farber Cancer Institute tracking 146 patients referred for 177Lu-PSMA-617 between May and October 2022 found the median time from tumour-board review to first treatment cycle rose from 41 days in May to 96 days in October as supply tightened; 35% of patients (45 of 146) started or continued a different therapy rather than wait, and 5% of approved patients (6 of 127) died during the wait. A 2022 international SNMMI survey of prostate cancer theranostics sites found a mean PSMA PET waiting time of 17±16 days (median 10, range 1-120), with the longest waits reported in Africa, and one-third of responding centres saying they lacked sufficient PET imaging capacity to meet demand.\n\nImaging-capacity concentration compounds the problem: a UK health-system-readiness review found only ten centres nationally offer gallium-68 DOTATATE/TOC PET-CT for neuroendocrine tumours, nine of them in or around London, forcing many patients to travel long distances simply to be assessed for eligibility before any decision about treatment itself.","asOf":"2026-09-22","links":[{"label":"IQVIA Institute: Developing efficient patient referral pathways for radioligand therapies (2025)","url":"https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/developing-efficient-patient-referral-pathways-for-radioligand-therapies"},{"label":"Targeted Oncology: Oncologists encounter challenges accessing PSMA-targeted therapy (Dana-Farber data)","url":"https://www.targetedonc.com/view/oncologists-encounter-challenges-to-accessing-psma-targeted-therapy-in-prostate-cancer"},{"label":"A 2022 international survey on the status of prostate cancer theranostics (JNM)","url":"https://jnm.snmjournals.org/content/64/1/47"},{"label":"Health system readiness for radioligand therapy in the UK: service provision","url":"https://www.healthsystemreadiness.com/app/uploads/Health-system-readiness-for-radioligand-therapy-in-the-UK-Service-provision.pdf"}],"tags":["access","referral","care pathway"],"related":["b-hot-lab-capacity","b-authorized-user-shortage","b-reimbursement-coding","ga-68","lu-177"],"indications":["prostate-mcrpc","neuroendocrine"],"sections":[],"technologies":["psma-pet","sstr-pet","radiopharmacy-network"],"targets":[],"drugs":["pluvicto","ga68-psma-11","ga68-dotatate"],"companies":[],"institutions":["dana-farber","snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"access-delivery","severity":"major","metrics":[{"label":"Minimum referral-to-treatment-initiation time for mCRPC radioligand therapy (Germany, France, Italy, China)","value":"7–11 weeks, depending on country","url":"https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/developing-efficient-patient-referral-pathways-for-radioligand-therapies"},{"label":"Dana-Farber: median tumour-board-to-cycle-1 wait, May vs October 2022","value":"41 days → 96 days","url":"https://www.targetedonc.com/view/oncologists-encounter-challenges-to-accessing-psma-targeted-therapy-in-prostate-cancer"},{"label":"Dana-Farber cohort: patients who switched to a different therapy while waiting","value":"35% (45 of 146)","url":"https://www.targetedonc.com/view/oncologists-encounter-challenges-to-accessing-psma-targeted-therapy-in-prostate-cancer"},{"label":"Dana-Farber cohort: approved patients who died before starting treatment","value":"5% (6 of 127)","url":"https://www.targetedonc.com/view/oncologists-encounter-challenges-to-accessing-psma-targeted-therapy-in-prostate-cancer"},{"label":"Mean PSMA PET wait time, international 2022 survey","value":"17±16 days (median 10, range 1–120)","url":"https://jnm.snmjournals.org/content/64/1/47"},{"label":"UK centres offering Ga-68 DOTATATE/TOC PET-CT for neuroendocrine tumours","value":"10 nationally, 9 in/around London","url":"https://www.healthsystemreadiness.com/app/uploads/Health-system-readiness-for-radioligand-therapy-in-the-UK-Service-provision.pdf"}],"causes":["The referral pathway crosses multiple specialties (urology/oncology, nuclear medicine, radiology) with no universally standardised handoff or shared ownership.","PSMA- and SSTR-PET imaging capacity, which is required to confirm eligibility, is concentrated at a small number of centres, often geographically distant from the referring clinic.","Community oncology and urology clinics frequently lack the NRC/Agreement-State licensure and hot-lab infrastructure to administer the therapy themselves, so patients must be referred out.","Disease can progress or the patient's clinical status can change during the referral-to-treatment interval, sometimes invalidating the original eligibility scan."],"currentEfforts":["IQVIA Institute's proposed streamlined seven-step RLT referral pathway, estimated to cut referral-to-treatment time by one to four weeks depending on country and starting point.","Multidisciplinary tumour-board models bringing referring physicians, nuclear medicine physicians and radiologists together earlier in the pathway.","Ordering PSMA PET scans earlier in the disease course (before frank progression) to avoid the scan itself becoming the bottleneck at the point of eligibility.","UK NHS and other national health-system readiness reviews assessing where new PET-CT and radioligand therapy capacity is most needed."],"successLooksLike":"A defined, resourced multidisciplinary referral pathway that gets an eligible patient from suspected progression to first radioligand therapy cycle in under four weeks, everywhere, not only at flagship academic centres.","route":"/bottlenecks/b-site-readiness-referral/"}
{"id":"b-radioactive-waste-regulation","kind":"bottleneck","name":"Radioactive waste handling and disposal regulation","aka":[],"tldr":"Every radioactive treatment leaves behind radioactive waste, such as used vials and, for a short time, the patient's own urine, which has to be safely stored until it stops being radioactive. The rules and the physical space needed for this differ from hospital to hospital and country to country, and building enough of that safe storage takes time.","summary":"US NRC rule 10 CFR 35.92 allows medical licensees to hold low-level radioactive waste for 'decay-in-storage' -- keeping it until a survey shows its radiation level is indistinguishable from background, then disposing of it as ordinary or medical waste -- but only for byproduct material with a physical half-life under 120 days. Most therapeutic isotopes qualify (lutetium-177's 6.65-day half-life decays in weeks), but contaminants complicate this: NRC guidance on Lutathera and Pluvicto notes that the metastable isotope lutetium-177m, with a 161-day half-life, can be present at roughly 0.02% of total activity and, when detected, must instead be handled as formal low-level radioactive waste under 10 CFR Part 20, a different and more burdensome disposal route.\n\nLow-level radioactive waste itself is classified by the NRC into Classes A, B and C by hazard; Class A, the least hazardous, makes up about 96% of total LLRW volume. A UK health-system readiness review lists radioactive-waste management -- decay-tank capacity, shielded 'hot' toilets for patients who have received a therapeutic dose, and staying within site-specific disposal limits -- as one of five mandatory steps any facility must have in place before it can deliver radioligand therapy at all, alongside licensing, imaging, treatment planning and follow-up.\n\nRegulatory fragmentation adds friction on top of the physical constraint: in the US, medical radioactive-material licensing is split between the NRC directly and 39 'Agreement States' that have taken on their own licensing authority, so requirements are not identical nationwide, and a site opening a new radioligand therapy programme must navigate whichever regime applies locally, often adding months to programme start-up alongside the physical build-out of shielded waste storage.","asOf":"2026-09-22","links":[{"label":"NRC: Decay-in-storage (DIS) of low-level radioactive waste, toolbox guidance","url":"https://www.nrc.gov/materials/toolboxes/llrw/decay-in-storage"},{"label":"NRC STC-22-074: Medical use, radiation safety and waste guidance for Lu-177 (Lutathera/Pluvicto)","url":"https://scp.nrc.gov/asletters/tech/sp22074.pdf"},{"label":"NRC: Low-level radioactive waste (LLRW) toolbox overview and classification","url":"https://www.nrc.gov/materials/toolboxes/llrw-waste"},{"label":"Establishing a robust radioligand therapy programme (licensing and Agreement State detail)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10905220/"},{"label":"Health system readiness for radioligand therapy in the UK: service provision","url":"https://www.healthsystemreadiness.com/app/uploads/Health-system-readiness-for-radioligand-therapy-in-the-UK-Service-provision.pdf"}],"tags":["regulation","waste disposal","radiation safety"],"related":["b-hot-lab-capacity","b-site-readiness-referral","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","radiopharmacy-network","lu177-radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"regulation-manufacturing","severity":"moderate","metrics":[{"label":"Maximum half-life NRC allows for medical decay-in-storage of radioactive waste (10 CFR 35.92)","value":"under 120 days","url":"https://www.nrc.gov/materials/toolboxes/llrw/decay-in-storage"},{"label":"Lutetium-177m contaminant activity in Lutathera/Pluvicto (161-day half-life, requires formal LLW disposal if detected)","value":"~0.02% of total Lu-177 activity","url":"https://scp.nrc.gov/asletters/tech/sp22074.pdf"},{"label":"Share of total US low-level radioactive waste volume that is Class A (least hazardous)","value":"~96%","url":"https://www.nrc.gov/materials/toolboxes/llrw-waste"},{"label":"US states with their own ('Agreement State') authority to license medical radioactive materials, as of 2024","value":"39 states","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10905220/"}],"causes":["Decay-tank and shielded-toilet capacity is a fixed physical build-out at each site, so it does not scale automatically with rising patient volume.","US medical radioactive-material licensing is split between the NRC and 39 individual Agreement States, producing inconsistent requirements across the country.","Longer-lived contaminants generated during isotope production (such as lutetium-177m) fall outside the simple decay-in-storage rule and require a separate, more burdensome low-level-waste disposal pathway.","New alpha-emitter therapies introduce longer-lived daughter radionuclides in the decay chain, which existing decay-in-storage assumptions built around beta emitters do not automatically cover."],"currentEfforts":["NRC Regulatory Issue Summary 2004-17 (revised) clarifying performance-based decay-in-storage criteria, removing the older fixed ten-half-life holding requirement in favour of a background-radiation survey standard.","Site-level engineering firms offering modular decay-tank retrofits to expand waste-storage capacity without a full facility rebuild.","UK and other national health-system readiness frameworks setting out waste-management capacity as an explicit, checkable prerequisite for opening a radioligand therapy service."],"successLooksLike":"Harmonised, performance-based radioactive-waste rules that scale predictably with a site's radioligand therapy volume, so waste-handling capacity is planned alongside clinical capacity rather than becoming a late, site-specific licensing surprise.","route":"/bottlenecks/b-radioactive-waste-regulation/"}
{"id":"b-rlt-trial-capacity","kind":"bottleneck","name":"Clinical trial capacity for radioligand therapy","aka":[],"tldr":"There are so many new radioactive cancer drugs now being tested that the trials themselves compete with each other, and with approved treatments, for the same scarce radioactive material, the same specially licensed hospital rooms, and the same trained staff. Sometimes a trial has to pause enrolling new patients simply because the isotope has run out.","summary":"Radioligand therapy's clinical pipeline has grown faster than the trial infrastructure needed to run it: industry analyses describe more than 200 lutetium-177-based radiopharmaceutical therapy trials of all phases in progress, including a large share of all active phase 3 radiopharmaceutical therapy trials underway worldwide. Because trial doses and commercial doses are drawn from the same limited isotope supply, a shortage hits trials directly: in June 2024, Bristol Myers Squibb's RayzeBio paused new-patient enrolment in the phase 3 ACTION-1 trial of RYZ101 (225Ac-DOTATATE) because it could not secure enough actinium-225, with a trial investigator noting there was only one Ac-225 supplier for the entire global study; patients already enrolled continued treatment while the company worked to bring on-site production online.\n\nSite-level capacity compounds the isotope constraint. A clinical-operations guide to radiopharmaceutical trials notes that qualifying a site can take several months longer than for a conventional drug trial, because sites need an active radioactive-materials licence, shielded rooms, dedicated patient toilets, imaging-camera qualification (dose calibrator checks, dummy deliveries), and pharmacy staff specifically trained to receive time-critical, non-reschedulable shipments; some radiopharmaceuticals also require ordering a month or more in advance, so a patient's slot can be blocked by another patient's ongoing treatment cycle. The same nuclear medicine departments that run these trials are also treating growing numbers of commercial Pluvicto and Lutathera patients, so trial and standard-of-care patients increasingly compete for the same limited administration slots at the same centres.\n\nBecause a no-show wastes a dose that can cost tens of thousands of dollars and cannot be re-used, site readiness guidance now stresses building slack into scheduling and engaging nuclear medicine leadership early, on top of the underlying isotope-supply constraint that no amount of site-level planning alone can fix.","asOf":"2026-09-22","links":[{"label":"FiercePharma: BMS and RayzeBio halt radiotherapy trial enrollment after isotope runs scarce","url":"https://www.fiercepharma.com/pharma/bms-and-rayzebio-halt-radiotherapy-trial-enrollment-after-isotope-runs-scarce"},{"label":"Preparing clinical sites for radiopharmaceutical trials (SCRS)","url":"https://myscrs.org/preparing-clinical-sites-radiopharmaceutical-trials/"},{"label":"Radioligand therapy manufacturing capacity: the CDMO and isotope-supply constraint (industry analysis)","url":"https://intuitionlabs.ai/articles/radioligand-therapy-manufacturing-capacity"}],"tags":["clinical trials","capacity","isotope supply"],"related":["b-ac225-supply","b-hot-lab-capacity","b-site-readiness-referral","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain","targeted-alpha-therapy","lu177-radioligand-therapy"],"targets":[],"drugs":["ryz101","pluvicto","lutathera"],"companies":["rayzebio","bms","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["action-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"stage":"trials","severity":"major","metrics":[{"label":"Lutetium-177 radiopharmaceutical therapy trials of all phases reported in progress (industry analysis)","value":">200","url":"https://intuitionlabs.ai/articles/radioligand-therapy-manufacturing-capacity"},{"label":"RayzeBio (BMS) paused new-patient enrolment in phase 3 ACTION-1 trial","value":"June 2024, cited cause: actinium-225 shortage, single global supplier","url":"https://www.fiercepharma.com/pharma/bms-and-rayzebio-halt-radiotherapy-trial-enrollment-after-isotope-runs-scarce"}],"causes":["Trial doses and commercial doses are drawn from the same constrained global isotope supply (particularly actinium-225 and, to a lesser extent, lutetium-177), so a supply shortfall hits both simultaneously.","Radiopharmaceutical trial sites typically take several months longer to qualify than conventional drug trial sites, because of radioactive-materials licensing, shielded-room construction, and imaging-equipment qualification requirements.","Nuclear medicine departments running trials are also treating a growing volume of approved standard-of-care patients, creating direct scheduling competition for the same hot labs and administration slots.","A missed or cancelled patient appointment wastes an individually manufactured, non-reschedulable dose that can cost tens of thousands of dollars, so scheduling slack has to be built in at a cost most conventional trials do not bear."],"currentEfforts":["BMS/RayzeBio advancing on-site accelerator-based actinium-225 production specifically to de-risk ACTION-1 and its wider RYZ101 programme after the 2024 enrolment pause.","Novartis and other sponsors building dedicated, multi-site radioligand therapy manufacturing capacity ahead of pivotal trial readouts, partly to protect trial as well as commercial supply.","Specialist clinical-operations guidance for radiopharmaceutical trial site readiness, recommending early engagement with nuclear medicine leadership and explicit resource-allocation planning between trial and standard-of-care caseloads."],"successLooksLike":"Isotope allocation and site capacity for clinical trials are planned and, where necessary, ring-fenced separately from commercial supply, so a manufacturing or feedstock shortage no longer forces a phase 3 trial to pause enrolment.","route":"/bottlenecks/b-rlt-trial-capacity/"}
{"id":"opendose","kind":"collection","name":"OpenDose","aka":[],"tldr":"A free online resource that lets nuclear medicine physicists look up how much radiation dose different organs receive from radioactive drugs, instead of everyone recalculating it from scratch.","summary":"OpenDose is a collaboration of about 18 international research teams that produces and shares specific absorbed fractions (SAFs) and S values for internal dosimetry, calculated with six Monte Carlo radiation-transport codes (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX and PENELOPE) run in parallel so results can be cross-checked. Data are generated for the source/target region combinations of the ICRP Publication 110 adult reference phantoms (male and female), with radionuclide decay data taken from ICRP Publication 107, and are stored in a relational database with their statistical uncertainties for traceability.\n\nThe website displays interactive plots of S values for 1,252 radionuclides and lets users download the underlying data as CSV. As of the project's 2020 description it held over 11 million SAF entries spanning 2 phantom models, 141 source regions, 172 target regions and 91 energies. The collaboration also aims to extend the work to voxel-based (patient-specific) dosimetry models and to publish software and educational material alongside the data.\n\nFor a radiopharmaceutical record in this graph, OpenDose is most useful as the traceable source of the physical dosimetry inputs (S values, SAFs) that feed patient dose calculations for isotopes such as lutetium-177 or actinium-225, complementing but not replacing clinical dosimetry guidelines.","asOf":"2026-09-22","links":[{"label":"OpenDose project mirror","url":"https://opendose.polsl.pl/project/"},{"label":"OpenDose S values tool","url":"https://opendose.polsl.pl/svalues/"},{"label":"Chauvin et al., J Nucl Med 2020: OpenDose: Open-Access Resource for Nuclear Medicine Dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7539649/"}],"tags":["dosimetry","open data","physics"],"related":["lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://opendose.polsl.pl/project/","holds":"Specific absorbed fractions (SAFs) and S values for internal dosimetry across 1,252 radionuclides, computed with six Monte Carlo codes on the ICRP 110 adult reference phantoms; downloadable as CSV, with a bibliography and lecture material.","license":"Free public access for viewing and CSV download; the collaboration is open to new contributing research teams. No formal open-data licence is stated on the site.","maintainer":"OpenDose collaboration, an international network of academic nuclear medicine physics groups (coordination includes INSERM, Toulouse); mirrored by Politechnika Śląska (Silesian University of Technology, Poland).","route":"/collections/opendose/"}
{"id":"icrp-publications","kind":"collection","name":"ICRP publications and dose coefficient databases","aka":[],"tldr":"The international body that sets the reference numbers used to work out how much radiation dose a patient, worker or member of the public gets, published as reports and downloadable spreadsheets.","summary":"The International Commission on Radiological Protection (ICRP) publishes Annals of the ICRP, the series that includes the reference decay-data compilation (Publication 107), the reference phantom anatomy (Publication 110) used by dosimetry projects such as OpenDose, and the successive compendia of dose coefficients for intakes of radionuclides by workers and the public (Publications 68, 72, 119, 130, 134, 137, 141, 151, 158 and related Occupational Intakes of Radionuclides and Public Intakes of Radionuclides series).\n\nAlongside the journal articles, ICRP releases free companion tools: a Dose Viewer mobile app, Electronic Annex/Data Viewer packages for the OIR and PIR series, an Excel-based viewer for Publication 116 external dose conversion coefficients, an EDC viewer for Publication 144 environmental dose-rate coefficients, and BiotaDC, a browser tool for non-human biota dose coefficients (Publication 136). Some older compilations were issued as standalone CDs (ICRP CD1, CD3).\n\nFor this graph, ICRP material is the primary reference for the physical dose coefficients that regulatory dose limits, radiopharmacy shielding calculations and internal dosimetry software ultimately rest on. The journal articles themselves sit behind a SAGE subscription/pay-per-issue paywall; the calculators, viewers and apps are free.","asOf":"2026-09-22","links":[{"label":"ICRP: Publications","url":"https://www.icrp.org/page.asp?id=5"},{"label":"ICRP: Dose Assessment Resources (viewers, apps, datasets)","url":"https://icrp.org/page.asp?id=505"},{"label":"ICRP Publication 107: Nuclear Decay Data for Dosimetric Calculations","url":"https://www.icrp.org/publication.asp?id=ICRP%20Publication%20107"}],"tags":["dosimetry","regulation","physics"],"related":["opendose"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://www.icrp.org/page.asp?id=5","holds":"The Annals of the ICRP publication series (dose coefficients for workers, the public and patients; reference phantoms; decay data) plus free dose-viewer apps, Excel/CSV datasets and calculators tied to specific ICRP publications.","license":"Annals of the ICRP articles are sold/subscribed through SAGE Publications; the dose-coefficient datasets, viewers and apps listed on icrp.org are free to download and use.","maintainer":"International Commission on Radiological Protection (ICRP), an independent, UK-registered scientific commission.","route":"/collections/icrp-publications/"}
{"id":"nrc-regulations-part35","kind":"collection","name":"US NRC 10 CFR Part 35 (Medical Use of Byproduct Material)","aka":[],"tldr":"The US federal rulebook that says which doctors and hospitals are allowed to give patients radioactive drugs, and what safety checks they must do.","summary":"Title 10, Part 35 of the US Code of Federal Regulations is the US Nuclear Regulatory Commission's rule set governing the medical use of byproduct (radioactive) material. It covers licensing of authorised users, authorised nuclear pharmacists and authorised medical physicists (Subparts A-C); unsealed material used without a written directive, such as diagnostic uptake and imaging studies (Subpart D); unsealed material requiring a written directive, i.e. most therapeutic radiopharmaceuticals (Subpart E); manual brachytherapy (Subpart F); sealed diagnostic sources (Subpart G); teletherapy and afterloader units (Subpart H); other medical uses (Subpart K, section 35.1000); and recordkeeping, reporting and enforcement (Subparts L-N).\n\nPart 35 sets the practical requirements that shape how lutetium-177, actinium-225, iodine-131 and other therapeutic radiopharmaceuticals are prescribed and administered in the United States: written directives, dose measurement before administration, medical event reporting thresholds, and patient-release criteria after therapy (35.75). NRC licenses cover roughly 40% of medical byproduct-material use directly; the remainder is regulated by 39 Agreement States that adopt compatible rules, so Part 35 also functions as the de facto national baseline.\n\nThe regulation text itself is freely available and is a primary source for approvals-adjacent facts (dose thresholds, reporting triggers) that should be cited directly rather than paraphrased from secondary summaries.","asOf":"2026-09-22","links":[{"label":"eCFR: 10 CFR Part 35 — Medical Use of Byproduct Material","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"},{"label":"NRC: FAQs about licensing medical uses under Part 35","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/faqs-part35"}],"tags":["regulation","United States","safety"],"related":["lu-177","ac-225","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35","holds":"The full current text of 10 CFR Part 35, all subparts (licensing, technical requirements, diagnostic and therapeutic unsealed material, brachytherapy, teletherapy, records, reports, enforcement), continuously updated by the Electronic Code of Federal Regulations.","license":"US federal regulatory text; public domain, freely reproducible.","maintainer":"US Nuclear Regulatory Commission (NRC), published via the Electronic Code of Federal Regulations (eCFR), a joint project of the National Archives and the Government Publishing Office.","route":"/collections/nrc-regulations-part35/"}
{"id":"iaea-isotope-databases","kind":"collection","name":"IAEA nuclear data and isotope databases","aka":[],"tldr":"A set of free online tools from the UN's nuclear agency that show the physical properties of every known radioactive atom, including the ones used in cancer scans and treatments.","summary":"The IAEA Nuclear Data Section maintains several linked, free web tools. The Live Chart of Nuclides (also an offline mobile app) gives an interactive chart of nuclear structure and decay data drawn mainly from the Evaluated Nuclear Structure Data Files (ENSDF), including half-lives, branching ratios, gamma-ray energies and intensities, and decay-scheme diagrams for essentially all known nuclides, with a Python API and CSV download service. A companion Medical Isotope Browser focuses on production routes and yield calculations for medically relevant isotopes, and a Decay Data Library Comparison tool lets users check discrepancies between evaluated libraries.\n\nThese tools underpin the physical constants (half-life, emission type and energy, branching ratio) that isotope records in this graph cite, and are also the reference the IAEA's own Rays of Hope initiative and Member State technical cooperation programmes use when planning isotope production and supply.\n\nAccess is free and does not require registration; the underlying evaluated data files (ENSDF and related libraries) are curated through the international Network of Nuclear Structure and Decay Data Evaluators that the IAEA coordinates.","asOf":"2026-09-22","links":[{"label":"IAEA Live Chart of Nuclides","url":"https://nds.iaea.org/relnsd/vcharthtml/VChartHTML.html"},{"label":"IAEA Nuclear Data Section: Global overview (databases and web applications)","url":"https://nds.iaea.org/indc/docs/presentations/INDC-2024-Global-overview.pdf"},{"label":"IAEA Livechart Data Download API guide","url":"https://www-nds.iaea.org/relnsd/vcharthtml/api_v0_guide.html"}],"tags":["isotopes","physics","open data"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iaea"],"pathways":[],"terms":["half-life"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://nds.iaea.org/relnsd/vcharthtml/VChartHTML.html","holds":"Nuclear structure and decay data (half-lives, decay modes, branching ratios, gamma/particle emission energies and intensities) for essentially all known nuclides, plus a medical isotope browser for production yield estimates and a decay-data library comparison tool.","license":"Free public access; underlying evaluated data (ENSDF and related libraries) are curated by an international network of national data centres coordinated by the IAEA.","maintainer":"IAEA Nuclear Data Section, International Atomic Energy Agency.","route":"/collections/iaea-isotope-databases/"}
{"id":"snmmi-procedure-standards","kind":"collection","name":"SNMMI Procedure Standards","aka":[],"tldr":"The US nuclear medicine society's rulebooks for how to correctly perform each type of scan or radioactive treatment, so results are comparable between hospitals.","summary":"The SNMMI Committee on Procedure Standards maintains around 80 procedure standards and practice guidelines covering nuclear medicine imaging and radionuclide therapy procedures, from FDG PET/CT and bone scintigraphy to newer documents such as the SNMMI/ACNM guideline on post-treatment imaging of 177Lu-based radiopharmaceutical therapies (2025) and joint SNMMI/EANM/ASNC/ACNM guidance on 18F-flurpiridaz PET myocardial perfusion imaging (2025). Many standards are developed jointly with EANM and other national societies (ANZSNM, CANM, CSNM) so that the same procedure recommendations apply across regions.\n\nEach document specifies patient preparation, tracer administration, acquisition protocol, processing, interpretation and reporting elements, aiming to standardise practice across institutions well enough that multicentre trial and registry data are comparable. Standards go through a public comment period before being formally approved.\n\nThe documents are freely viewable and downloadable from the SNMMI website for individual professional use; the site explicitly prohibits unauthorised copying or reprinting, so they are open-access in practice but not openly licensed.","asOf":"2026-09-22","links":[{"label":"SNMMI: Procedure Standards","url":"https://snmmi.org/Web/Web/Clinical-Practice/Procedure-Standards/Procedure-Standards.aspx"},{"label":"SNMMI: General Imaging 6.0 procedure standard (example)","url":"https://snmmi.org/Web/Web/Clinical-Practice/Procedure-Standards/Standards/General-Imaging-6-0.aspx"}],"tags":["guidelines","practice standards"],"related":["eanm-guidelines","f-18","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://snmmi.org/Web/Web/Clinical-Practice/Procedure-Standards/Procedure-Standards.aspx","holds":"About 80 procedure standards and practice guidelines for nuclear medicine imaging and radionuclide therapy procedures, each covering patient preparation, tracer administration, acquisition, processing, interpretation and reporting.","license":"Free to view and download for individual professional use; SNMMI states that copying or unauthorised printing of the documents is prohibited.","maintainer":"Society of Nuclear Medicine and Molecular Imaging (SNMMI), Committee on Procedure Standards.","route":"/collections/snmmi-procedure-standards/"}
{"id":"eanm-guidelines","kind":"collection","name":"EANM Guidelines","aka":[],"tldr":"The European nuclear medicine society's free rulebooks for how to correctly perform each type of scan or radioactive treatment.","summary":"The European Association of Nuclear Medicine (EANM) publishes and maintains a repository of procedure guidelines organised by organ system and application area (oncology, cardiovascular, central nervous system, paediatric, therapy, and more), plus the free-to-access European Nuclear Medicine Guide, a comprehensive handbook first launched in October 2018 (2026 edition released) covering basic science, in vivo imaging, hybrid imaging, radionuclide-guided surgery, dosimetry, radionuclide therapy and radiation protection. Many guidelines are developed jointly with SNMMI and other national societies, for example the joint EANM/SNMMI FDG PET/CT tumour-imaging guideline (version 3.0, 2025) and the EANM/SNMMI Tau PET recommendations (2026).\n\nEANM guidelines are distinct from EANM's journal publishing: EANM ended its long-standing publishing partnership with Springer Nature and the EJNMMI journal family at the end of 2024, and in 2025 launched two of its own open-access journals with Elsevier, The EANM Journal and EANM Innovation. The guidelines repository is unaffected by that change and continues to sit on eanm.org.\n\nAll guideline documents and the European Nuclear Medicine Guide are free to read online or via a companion mobile app, with no paywall, making EANM's guidance the most openly accessible procedural reference in the field alongside SNMMI's.","asOf":"2026-09-22","links":[{"label":"EANM: Guidelines","url":"https://eanm.org/publications/guidelines/"},{"label":"EANM: European Nuclear Medicine Guide","url":"https://eanm.org/publications/useful-resources/nuclear-medicine-guide/"},{"label":"EANM: Release of the 2026 European Nuclear Medicine Guide","url":"https://eanm.org/news/release-of-the-2026-european-nuclear-medicine-guide-jan-2026/"}],"tags":["guidelines","practice standards"],"related":["snmmi-procedure-standards"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["eanm"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://eanm.org/publications/guidelines/","holds":"Procedure guidelines for nuclear medicine imaging and radionuclide therapy organised by clinical area (oncology, cardiovascular, CNS, paediatric, therapy and more), plus the free European Nuclear Medicine Guide handbook and app.","license":"Free to read online and via the companion app; no cost or registration.","maintainer":"European Association of Nuclear Medicine (EANM), in collaboration with the European Union of Medical Specialists/European Board of Nuclear Medicine (UEMS/EBNM) for the European Nuclear Medicine Guide.","route":"/collections/eanm-guidelines/"}
{"id":"imaging-data-commons","kind":"collection","name":"NCI Imaging Data Commons (IDC)","aka":[],"tldr":"A free, US government-run online library of cancer scan images that any researcher can browse and download without asking permission first.","summary":"The Imaging Data Commons (IDC) is a cloud-based repository within the US National Cancer Institute's Cancer Research Data Commons (CRDC), launched to support cancer imaging research on the cloud as part of the Cancer Moonshot. It holds over 100 TB of radiology, histopathology and fluorescence slide microscopy images together with image-derived data such as annotations, segmentations and quantitative measurements, plus accompanying clinical data, all harmonised to the DICOM standard.\n\nAll data in IDC is publicly available with no registration or access request required, distinguishing it from most other CRDC nodes that gate genomic or clinical data behind data-use agreements. The web portal integrates a customised OHIF viewer supporting visualisation of DICOM segmentation and radiotherapy structure sets, and lets users define patient cohorts from metadata and export them for downstream analysis alongside other CRDC data types (genomic, proteomic).\n\nFor radiopharmaceutical research, IDC is a source of curated PET/CT and other molecular imaging collections (including some PSMA and FDG PET datasets contributed by NCI-funded studies or individual investigators) that can be used to develop and validate quantitative imaging biomarkers without needing bespoke data-sharing agreements with individual institutions.","asOf":"2026-09-22","links":[{"label":"NCI Imaging Data Commons portal","url":"https://portal.imaging.datacommons.cancer.gov/"},{"label":"NCI CRDC: Imaging Data Commons overview","url":"https://datacommons.cancer.gov/repository/imaging-data-commons"},{"label":"Fedorov et al., Cancer Res 2021: NCI Imaging Data Commons","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8373794/"}],"tags":["open data","imaging","United States"],"related":["tcia"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"url":"https://portal.imaging.datacommons.cancer.gov/","holds":"Over 100 TB of publicly available, DICOM-harmonised cancer imaging data (radiology, histopathology, fluorescence slide microscopy) with image-derived annotations, segmentations and quantitative measurements, plus linked clinical data, co-located with cloud analysis tools.","license":"All data are publicly available with no registration or access request, subject to NCI data-use agreements specific to individual contributed datasets.","maintainer":"US National Cancer Institute (NCI), as a node of the Cancer Research Data Commons (CRDC).","route":"/collections/imaging-data-commons/"}
{"id":"ejnmmi","kind":"journal","name":"European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI)","aka":["EJNMMI","European Journal of Nuclear Medicine"],"tldr":"A long-running European medical journal that publishes new research on radioactive scans and radioactive treatments.","summary":"EJNMMI traces back to the European Journal of Nuclear Medicine (EJNM), founded in 1975 and based in Hannover, Germany; it was renamed European Journal of Nuclear Medicine and Molecular Imaging and, according to Springer, was the official journal of the European Association of Nuclear Medicine (EANM) until December 2024. The journal covers clinical and scientific work in functional, metabolic and molecular investigation of disease: diagnostic and therapeutic radiopharmaceuticals, image-guided therapy, physics, dosimetry, radiation biology, radiochemistry and radiopharmacy, plus reviews, short communications and letters (it does not publish case reports).\n\nIn February and July 2025, EANM announced the end of its publishing partnership with Springer Nature and the EJNMMI journal family, and launched two of its own open-access journals with Elsevier — The EANM Journal and EANM Innovation — as the society's new flagship venues. EJNMMI itself continues to publish with Springer Nature independently of that society affiliation; papers citing pre-2025 EANM-endorsed guidelines will generally reference EJNMMI, while post-2025 EANM guidance is increasingly appearing in the new EANM journals instead.\n\nBecause of that transition, records in this graph should check the publication year of any paper before assuming EJNMMI carries current EANM endorsement.","asOf":"2026-09-22","links":[{"label":"EJNMMI home (Springer Nature)","url":"https://link.springer.com/journal/259"},{"label":"EJNMMI aims and scope","url":"https://link.springer.com/journal/259/aims-and-scope"},{"label":"50 years EJNM and EJNMMI (Eur J Nucl Med Mol Imaging, 2023)","url":"https://link.springer.com/article/10.1007/s00259-023-06361-7"},{"label":"EANM: EANM's new own journals (Feb 2025)","url":"https://eanm.org/news/eanms-new-own-journals-feb-2025/"}],"tags":["journal","nuclear medicine"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["eanm"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Springer Nature","url":"https://link.springer.com/journal/259","scope":"Nuclear medicine and molecular imaging: diagnostic and therapeutic radiopharmaceuticals, image-guided therapy, physics, dosimetry, radiochemistry and radiopharmacy.","access":"hybrid","founded":1975,"matchNames":["European Journal of Nuclear Medicine and Molecular Imaging","Eur J Nucl Med Mol Imaging","EJNMMI"],"route":"/journals/ejnmmi/"}
{"id":"theranostics-journal","kind":"journal","name":"Theranostics","aka":[],"tldr":"A fully free-to-read journal that publishes research combining diagnosis and treatment, including radioactive drugs.","summary":"Theranostics is a biweekly, fully open-access journal established in 2011 and published by Ivyspring International Publisher. It covers in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensors, systems biology and translational and personalised medicine — a broad remit that in practice makes it one of the most frequently cited venues for new PET and SPECT radiotracers, radioligand therapy chemistry, and nanomedicine-based theranostic agents.\n\nArticles are published under a CC BY-NC licence and are immediately free to read, with no subscription barrier; the journal states full compliance with NIH public access requirements. It is indexed in Web of Science (Science Citation Index Expanded), MEDLINE/PubMed and Scopus.\n\nAccording to the journal's own indexing page, its Journal Citation Reports impact factor was 12.4 for the 2024 JCR release, up from 11.556 in the 2022 release; third-party trackers report further increases in more recent JCR cycles, which readers should verify against Clarivate directly given how fast the metric has moved.","asOf":"2026-09-22","links":[{"label":"Theranostics home","url":"https://www.thno.org/"},{"label":"Theranostics: Index and ranking (impact factor history)","url":"https://www.thno.org/indexrank"}],"tags":["journal","open access","theranostics"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Ivyspring International Publisher","url":"https://www.thno.org/","scope":"Theranostics: molecular imaging, molecular therapeutics, image-guided therapy, biosensors, nanomedicine and translational/personalised medicine.","access":"open-access","founded":2011,"impactFactor":{"value":12.4,"year":2024,"source":"Theranostics journal, Index and ranking page (thno.org/indexrank), citing the 2024 Journal Citation Reports release"},"matchNames":["Theranostics"],"route":"/journals/theranostics-journal/"}
{"id":"clinical-nuclear-medicine","kind":"journal","name":"Clinical Nuclear Medicine","aka":["CNM"],"tldr":"A monthly US medical journal for doctors who use radioactive scans and treatments in everyday patient care.","summary":"Clinical Nuclear Medicine has been published since its first issue in June 1976, making it almost exactly contemporaneous with the first human FDG-PET images acquired that same year. It is a monthly journal from Lippincott Williams & Wilkins (Wolters Kluwer) aimed squarely at clinical practice: diagnostic interpretation, new tracers and imaging techniques, case-based teaching material, and correlation of nuclear medicine findings with other imaging modalities.\n\nIt sits alongside more basic-science-oriented titles such as the Journal of Nuclear Medicine and EJNMMI as one of the main clinical-practice venues in the field, and is frequently cited for case reports and imaging pearls involving PSMA PET, DOTATATE PET and other radiopharmaceutical-based studies that do not fit the format of a full clinical trial report.\n\nAccording to Wolters Kluwer's own journal page, its 2024 Journal Citation Reports impact factor was 9.6.","asOf":"2026-09-22","links":[{"label":"Clinical Nuclear Medicine (LWW journal home)","url":"https://journals.lww.com/nuclearmed/pages/default.aspx"},{"label":"Wolters Kluwer/Ovid: Clinical Nuclear Medicine journal page","url":"https://www.wolterskluwer.com/en/solutions/ovid/clinical-nuclear-medicine-235"},{"label":"PubMed: Historic images in nuclear medicine — the first issue of Clinical Nuclear Medicine (1976)","url":"https://pubmed.ncbi.nlm.nih.gov/24978339/"}],"tags":["journal","nuclear medicine","clinical"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Lippincott Williams & Wilkins (Wolters Kluwer)","url":"https://journals.lww.com/nuclearmed/pages/default.aspx","scope":"Clinical nuclear medicine practice: diagnostic imaging interpretation, new radiopharmaceuticals and tracers, case reports and teaching cases.","access":"subscription","founded":1976,"impactFactor":{"value":9.6,"year":2024,"source":"Wolters Kluwer/Ovid journal page for Clinical Nuclear Medicine"},"matchNames":["Clinical Nuclear Medicine","Clin Nucl Med"],"route":"/journals/clinical-nuclear-medicine/"}
{"id":"nuclear-medicine-and-biology","kind":"journal","name":"Nuclear Medicine and Biology","aka":["Nucl Med Biol","NMB"],"tldr":"A scientific journal for the chemistry side of radioactive drugs: how they are made, tested in cells and animals, and first tried in patients.","summary":"Nuclear Medicine and Biology began in 1973 as an Elsevier (then Pergamon Press) title and was rebranded in 1985 as Part B of the International Journal of Radiation Applications and Instrumentation before reverting to its current name; it is the official journal of the Society of Radiopharmaceutical Sciences. Its scope is radiopharmaceutical science across the full pipeline: automated and manual radiosynthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy and translational clinical studies of new targeted radiotracers, with editorial guidance that the importance of the biological target should be the primary justification for publication, ahead of chemistry novelty alone.\n\nIt is a natural venue for first-in-human biodistribution and dosimetry papers on new PET/SPECT tracers and for methods papers on radiolabelling chemistry, generator systems and quality control — material that is often too preliminary or too chemistry-focused for the large clinical journals.\n\nElsevier's ScienceDirect Insights page for the journal states an impact factor of 3.0 and a CiteScore of 6.9; third-party trackers place the equivalent Clarivate JCR value in the range of roughly 2.6-3.0 depending on the release year, so the exact figure should be checked against the current JCR release before being quoted precisely.","asOf":"2026-09-22","links":[{"label":"Nuclear Medicine and Biology (ScienceDirect journal home)","url":"https://www.sciencedirect.com/journal/nuclear-medicine-and-biology"},{"label":"Society of Radiopharmaceutical Sciences: Journal page","url":"https://www.srsweb.org/journal"},{"label":"Nuclear Medicine and Biology — history note (60 years of Applied Radiation and Isotopes / Pergamon journals)","url":"https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=922075"}],"tags":["journal","radiochemistry","radiopharmacy"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Elsevier","url":"https://www.sciencedirect.com/journal/nuclear-medicine-and-biology","scope":"Radiopharmaceutical science: synthesis, in vitro/ex vivo evaluation, in vivo biodistribution, radiopharmacology, radiopharmacy and translational clinical studies of radiotracers.","access":"hybrid","founded":1973,"impactFactor":{"value":3,"year":2024,"source":"Elsevier ScienceDirect journal insights page for Nuclear Medicine and Biology; cross-checked against journalsimpactfactors.com (2024 JCR-based value 3.0)"},"matchNames":["Nuclear Medicine and Biology","Nucl Med Biol"],"society":"Society of Radiopharmaceutical Sciences","route":"/journals/nuclear-medicine-and-biology/"}
{"id":"ejnmmi-radiopharmacy-and-chemistry","kind":"journal","name":"EJNMMI Radiopharmacy and Chemistry","aka":["EJNMMI Radiopharm Chem"],"tldr":"A specialist journal, launched in 2015, for the chemistry of making new radioactive imaging and therapy drugs.","summary":"EJNMMI Radiopharmacy and Chemistry launched in late October 2015 as a companion title within the EJNMMI journal family, aimed at chemists, pharmacists, biologists and basic scientists working on new imaging and radionuclide-based therapeutic agents. Its scope covers novel radionuclide production methods, radiochemistry and radiolabelling, new radiopharmaceuticals with first biological evaluation, and molecular imaging agents more broadly (including optical and MRI probes and hybrid probes), as well as best-practice and harmonisation guidance and legislative/regulatory position papers relevant to translating agents to the clinic.\n\nIt received its first Clarivate impact factor in 2023, covering the 2022 JCR release, at 4.6, and is indexed in the Emerging Sources Citation Index under chemistry, medicinal; radiology, nuclear medicine & medical imaging; and chemistry, inorganic & nuclear categories.\n\nAs a Springer Nature/SpringerOpen title, it is fully open access, distinguishing it from its parent journal EJNMMI, which is hybrid.","asOf":"2026-09-22","links":[{"label":"EJNMMI Radiopharmacy and Chemistry home (Springer)","url":"https://link.springer.com/journal/41181"},{"label":"EJNMMI Radiopharmacy and Chemistry aims and scope","url":"https://link.springer.com/journal/41181/aims-and-scope"},{"label":"Editorial launching EJNMMI Radiopharmacy and Chemistry (2016)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5843801/"},{"label":"EJNMMI Radiopharmacy and Chemistry obtains its first impact factor (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10368598/"}],"tags":["journal","radiochemistry","open access"],"related":["ejnmmi"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Springer Nature (SpringerOpen)","url":"https://link.springer.com/journal/41181","scope":"Radiopharmaceutical chemistry: radionuclide production, radiolabelling and radiosynthesis, new imaging and therapeutic agents, and regulatory/best-practice guidance for translating them to the clinic.","access":"open-access","founded":2015,"impactFactor":{"value":4.6,"year":2022,"source":"EJNMMI Radiopharmacy and Chemistry, PMC editorial announcing its first impact factor (PMC10368598)"},"matchNames":["EJNMMI Radiopharmacy and Chemistry","EJNMMI Radiopharm Chem"],"route":"/journals/ejnmmi-radiopharmacy-and-chemistry/"}
{"id":"journal-of-nuclear-cardiology","kind":"journal","name":"Journal of Nuclear Cardiology","aka":["JNC"],"tldr":"The official journal of the American nuclear cardiology society, covering heart scans that use radioactive tracers.","summary":"The Journal of Nuclear Cardiology has published since 1994 and is the official journal of the American Society of Nuclear Cardiology (ASNC); its founding editor was Barry L. Zaret and its current editor-in-chief is Marcelo Di Carli. It covers diagnostic interpretation, imaging equipment and radiopharmaceuticals used in nuclear cardiology, publishing original research, ASNC society guidelines, and discussion of the subspecialty's current and future role alongside competing cardiac imaging modalities.\n\nThe journal was published by Springer for most of its history and moved to Elsevier as publisher in collaboration with ASNC; both the journal's own and Wikipedia's account describe it as still the society's official publication. It is a natural venue for radiopharmaceutical records tied to myocardial perfusion imaging, for example 18F-flurpiridaz PET, and for guideline documents co-authored with SNMMI and ACNM.\n\nAccording to Wikipedia, citing the 2025 Journal Citation Reports (Clarivate, released 2026), its impact factor is 3.0, up from 2.7 in the prior (2024) release.","asOf":"2026-09-22","links":[{"label":"ASNC: Journal of Nuclear Cardiology","url":"https://www.asnc.org/news-publications/journal-of-nuclear-cardiology/"},{"label":"Journal of Nuclear Cardiology — Wikipedia","url":"https://en.wikipedia.org/wiki/Journal_of_Nuclear_Cardiology"}],"tags":["journal","cardiology","nuclear medicine"],"related":["f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"publisher":"Elsevier","url":"https://www.asnc.org/news-publications/journal-of-nuclear-cardiology/","scope":"Nuclear cardiology: myocardial perfusion imaging, cardiac PET and SPECT radiopharmaceuticals, diagnostic interpretation and society guidelines.","access":"subscription","founded":1994,"impactFactor":{"value":3,"year":2025,"source":"Wikipedia, Journal of Nuclear Cardiology, citing 2025 Journal Citation Reports (Clarivate, Web of Science)"},"matchNames":["Journal of Nuclear Cardiology","J Nucl Cardiol"],"society":"American Society of Nuclear Cardiology (ASNC)","route":"/journals/journal-of-nuclear-cardiology/"}
{"id":"bracco","kind":"company","name":"Bracco Imaging","aka":["Bracco Imaging S.p.A.","Bracco Group"],"tldr":"An Italian company that makes the dyes and tracers doctors use to see inside the body on X-ray, CT, MRI, ultrasound and PET/SPECT scans, and, through a subsidiary, some of the radioactive scans used to find prostate cancer.","summary":"Bracco Imaging is the diagnostics arm of the privately held Bracco Group (Milan, Italy), one of the largest suppliers of contrast media worldwide: iodinated X-ray/CT contrast agents, gadolinium-based MRI contrast agents, and ultrasound microbubble contrast (SonoVue/Lumason). Its move into nuclear medicine came through acquisition rather than in-house discovery: in 2019 Bracco Imaging bought Blue Earth Diagnostics, a UK/US company built around fluciclovine F-18 (Axumin), an amino-acid PET tracer for recurrent prostate cancer, for $450 million plus an earn-out, giving Bracco its first commercialised radiopharmaceutical.\n\nBlue Earth Diagnostics (id: blue-earth-diagnostics) operates as a semi-autonomous subsidiary under the Bracco Group umbrella and continues to expand the diagnostic oncology portfolio Bracco now depends on for nuclear medicine revenue, including PSMA-targeted radiohybrid (rhPSMA) imaging agents licensed from Scintomics and the Technical University of Munich. A sister company, Blue Earth Therapeutics, holds the worldwide rights to the therapeutic (177Lu-labelled) applications of the same rhPSMA chemistry, extending Bracco's nuclear medicine business from imaging into radioligand therapy for prostate cancer.\n\nBracco's core diagnostic imaging business (CT, MRI and ultrasound contrast) remains far larger by revenue than its nuclear medicine segment, but the group frames molecular imaging and theranostics as its main growth vector, positioning itself against GE HealthCare, Siemens Healthineers, Lantheus and Curium in nuclear pharmacy distribution and against Novartis and Telix in PSMA-targeted prostate cancer imaging and therapy.","status":"active","asOf":"2026-09-22","links":[{"label":"Bracco: our portfolio (nuclear medicine)","url":"https://www.bracco.com/en-us/our-portfolio"},{"label":"Bracco: our businesses (Blue Earth Diagnostics, Blue Earth Therapeutics)","url":"https://www.bracco.com/our-businesses"},{"label":"Bracco: oncology / rhPSMA (Blue Earth Therapeutics)","url":"https://www.bracco.com/en-us/oncology"},{"label":"FierceBiotech: Blue Earth Diagnostics sold to Bracco Imaging in $450M deal (2019)","url":"https://www.fiercebiotech.com/medtech/blue-earth-diagnostics-sold-to-bracco-imaging-450m-deal"},{"label":"Bracco: Bracco Imaging expands its portfolio of personalized diagnostics (2021, rhPSMA licence)","url":"https://www.bracco.com/article/bracco-imaging-expands-its-portfolio-personalized-diagnostics"}],"tags":["contrast media","diagnostics","prostate cancer imaging"],"related":["blue-earth-diagnostics","fluciclovine-f18","psma","prostate","psma-pet","f-18","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Milan, Italy","country":"IT","companyType":"diagnostics","website":"https://www.bracco.com","founded":1927,"stage":"private-large","investors":[],"funding":[],"route":"/companies/bracco/"}
{"id":"life-molecular-imaging","kind":"company","name":"Life Molecular Imaging","aka":["LMI"],"tldr":"A company that makes Neuraceq, an injectable radioactive tracer that lights up Alzheimer's plaques on a PET brain scan, and is now owned by Lantheus.","summary":"Life Molecular Imaging (LMI) develops and commercialises F-18-labelled PET radiopharmaceuticals for neurodegenerative and cardiovascular disease. Its flagship product is Neuraceq (florbetaben F-18 injection), an amyloid-beta PET imaging agent approved in the United States, European Union, Canada, South Korea, China and Japan, used to estimate amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease, including to select patients eligible for amyloid-beta-directed therapies. LMI was previously a subsidiary of Life Healthcare Group Holdings.\n\nBeyond Neuraceq, LMI's pipeline includes an F-18 tau PET tracer (florzolotau/izaflortaucipir programmes referenced in company pipeline listings) and, following a June 2024 deal, global rights to a GRPR-targeted theranostic pair, 68Ga-DOTA-RM2 (diagnostic) and 177Lu-DOTA-RM2 (therapeutic), aimed at prostate, breast and other GRPR-expressing cancers.\n\nLantheus Holdings announced the acquisition of Life Molecular Imaging in January 2025 (upfront payment of $350 million plus up to $400 million in earn-out and milestone payments) and completed the roughly $789 million transaction in July 2025, giving Lantheus a commercial Alzheimer's disease diagnostic franchise and LMI's manufacturing and distribution network, which it has since been expanding within the United States (for example new production sites in Southern California and, via a partnership with SOFIE Biosciences, in Decatur, Illinois).","status":"active","asOf":"2026-09-22","links":[{"label":"Neuraceq (florbetaben F18 injection) product site","url":"https://neuraceq.com/"},{"label":"Lantheus: Lantheus to Acquire Life Molecular Imaging (Jan 2025)","url":"https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-acquire-life-molecular-imaging-upfront-payment-350"},{"label":"medpath: Lantheus completes $789 million acquisition of Life Molecular Imaging (2025)","url":"https://trial.medpath.com/news/lantheus-completes-789-million-acquisition-of-life-molecular-imaging-gains-fda-approved-alzheimer-s-diagnostic-agent"},{"label":"PR Newswire: Life Molecular Imaging expands Neuraceq production in Southern California (2025)","url":"https://www.prnewswire.com/news-releases/life-molecular-imaging-expands-neuraceq-florbetaben-f-18-injection-production-in-southern-california-302534927.html"},{"label":"BioSpace: Life Molecular Imaging expands Neuraceq production in Decatur, IL, with SOFIE Biosciences (2025)","url":"https://www.biospace.com/press-releases/life-molecular-imaging-expands-neuraceq-florbetaben-f-18-injection-production-in-decatur-il"}],"tags":["PET tracer","Alzheimer's imaging","amyloid PET"],"related":["lantheus","sofie-biosciences","grpr","f-18","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Berlin, Germany (Lantheus subsidiary, Boston, US commercial operations)","country":"DE","companyType":"radiopharma","website":"https://www.life-mi.com","founded":2013,"stage":"acquired","investors":[],"funding":[],"route":"/companies/life-molecular-imaging/"}
{"id":"advancell","kind":"company","name":"AdvanCell","aka":["AdvanCell Isotopes"],"tldr":"An Australian biotech building its own supply of the rare radioactive metal lead-212 so it can make alpha-particle cancer therapies, starting with one for prostate cancer.","summary":"AdvanCell (AdvanCell Isotopes) is a vertically integrated, clinical-stage radiopharmaceutical company headquartered in Australia with operations extending to North America. Its core strategy is to control the whole chain for lead-212 (212Pb)-based targeted alpha therapy: proprietary 212Pb isotope production technology, secure isotope supply, in-house manufacturing, and clinical development of 212Pb-labelled targeting molecules, rather than relying on external isotope suppliers as many alpha-therapy developers must.\n\nIts lead clinical candidate, ADVC001 (212Pb-PSMA-targeted radioligand therapy), is in a Phase II trial (NCT05720130) for metastatic prostate cancer. The company originated from work at the University of Newcastle, Australia (spun out around 2019), and has raised substantial venture financing to build out clinical and commercial manufacturing infrastructure, including a Series C round and a July 2026 oversubscribed and upsized Series D financing of US$315 million, backed by investors including Abingworth, Brandon Capital, Morningside, Sanofi Ventures, SV Ventures and Sofinnova-adjacent funds; proceeds are earmarked for advancing ADVC001 toward late-stage development and expanding manufacturing capacity.\n\nBecause lead-212 (via its parent thorium-228/radium-224 decay chain) has a much shorter half-life than actinium-225, AdvanCell's bet is that a dedicated, scaled production and logistics system for 212Pb can supply alpha emitters more reliably than the constrained global actinium-225 supply chain that its competitors depend on.","status":"active","asOf":"2026-09-22","links":[{"label":"AdvanCell Closes US $315 Million Oversubscribed Series D Financing (2026)","url":"https://www.advancell.com.au/news/advancell-closes-us-315-million-oversubscribed-series-d-financing-to-advance-targeted-alpha-therapies-and-expand-clinical-and-commercial-manufacturing-infrastructure/"},{"label":"AdvanCell company site","url":"https://www.advancell.com.au/"},{"label":"BioXconomy: AdvanCell lands $315m for prostate cancer drug (2026)","url":"https://www.bioxconomy.com/investment/advancell-lands-315m-to-solve-radiopharmaceutical-industry-s-biggest-constraint-"},{"label":"Brandon Capital: Advancell portfolio page","url":"https://brandoncapital.vc/portfolio/advancell/"}],"tags":["lead-212","targeted alpha therapy","prostate cancer"],"related":["psma","prostate-mcrpc","targeted-alpha-therapy","actinium-225-supply","ac-225","pb-212","ra-224"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Sydney, Australia (also Brisbane and Newcastle, Australia; San Francisco, US)","country":"AU","companyType":"radiopharma","website":"https://www.advancell.com.au","founded":2019,"stage":"growth","investors":[],"funding":[],"route":"/companies/advancell/"}
{"id":"ionetix","kind":"company","name":"IONETIX","aka":["Ionetix Corporation"],"tldr":"A Michigan company that builds compact superconducting particle accelerators and uses them to make radioactive materials for both diagnostic scans and cancer therapies, including two rare isotopes, actinium-225 and astatine-211.","summary":"IONETIX Corporation is a cyclotron technology and radioisotope manufacturing company founded in 2009, spun from accelerator physics developed at the MIT Plasma Science and Fusion Center. Its patented compact superconducting cyclotron, the ION-12SC, was originally built to produce N-13 ammonia (a cardiac PET perfusion tracer) close to the point of care under a pay-per-dose model, and IONETIX has since built a network of such cyclotrons at or near PET programmes, also producing F-18 and Ga-68 diagnostic tracers.\n\nMore recently IONETIX has moved into cyclotron-based alpha-emitter production at a dedicated Alpha Isotope Manufacturing facility in Lansing, Michigan, the first commercial facility built exclusively for alpha-emitting radionuclides. It announced first production of actinium-225 (Ac-225) there in June 2024, describes itself as releasing GMP-grade Ac-225 to customers from late 2024, and began routine shipment of astatine-211 (At-211) in the US in September 2026, produced by irradiating bismuth-209 targets on a 30 MeV cyclotron; it states it is the first non-academic commercial US supplier of At-211. A second Ac-225 cyclotron with dual target stations, intended to allow continuous production scaling to more than 1 curie of Ac-225 per week, began construction in October 2024.\n\nIONETIX raised over $30 million in a 2026 private placement alongside a reverse-merger transaction with JDEV Acquisition Corp that took the company public, with funds earmarked for scaling isotope production and further developing its accelerator technology for medical, materials-testing and nuclear-energy applications. Its supply chain role sits alongside other emerging cyclotron-based alpha-emitter producers, competing on the specific bottleneck of actinium-225 and astatine-211 availability for targeted alpha therapy developers.","status":"active","asOf":"2026-09-22","links":[{"label":"IONETIX: Ionetix Completes $30 million+ Financing in a Go-Public Transaction (2026)","url":"https://ionetix.com/2026/04/21/ionetix-completes-30-million-financing-in-a-go-public-transaction/"},{"label":"IONETIX: about","url":"https://ionetix.com/about/"},{"label":"IONETIX: IONETIX Launches Commercial Actinium-225 Production (2024)","url":"https://ionetix.com/2024/06/07/ionetix-produces-first-batch-of-actinium-225/"},{"label":"IONETIX: Ionetix Begins Shipping Astatine-211 (2026)","url":"https://ionetix.com/2026/09/01/ionetix-begins-shipping-astatine-211-to-support-preclinical-and-clinical-trials/"},{"label":"IONETIX: second cyclotron construction for Ac-225 production (2024)","url":"https://ionetix.com/2024/10/17/ionetix-announces-start-of-construction-to-add-second-cyclotron-for-ac-225-production-at-its-alpha-isotope-manufacturing-facility/"}],"tags":["cyclotron","actinium-225","astatine-211","isotope supply"],"related":["actinium-225-supply","astatine-211-alpha-therapy","cyclotron-isotope-production","targeted-alpha-therapy","f-18","ga-68","n-13","ac-225","at-211"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Lansing, Michigan, US","country":"US","companyType":"radiopharma","website":"https://ionetix.com","founded":2009,"stage":"public","investors":[],"funding":[],"route":"/companies/ionetix/"}
{"id":"niowave","kind":"company","name":"Niowave","aka":["Niowave, Inc."],"tldr":"A Michigan company that produces medical radioactive materials, including some used for cancer treatment, using a superconducting particle accelerator instead of a nuclear reactor.","summary":"Niowave, Inc. is a Michigan-based developer of superconducting radiofrequency (SRF) electron linear accelerators, founded by Dr Terry Grimm and originally built on Department of Energy-funded accelerator R&D. Rather than a reactor, Niowave uses high-power superconducting electron linacs (its facility is licensed to run up to 40 MeV and 100 kW) to drive photonuclear reactions in target materials, producing isotopes via (gamma,n), (gamma,p) and photofission routes, including from uranium and radium targets, without the proliferation concerns associated with highly enriched uranium.\n\nIts stated therapeutic radioisotope programmes include strontium-90/yttrium-90 (its first commercial isotope, with what it describes as ongoing shipments to treat cancer patients using ISO 13485-certified hot cells and processing equipment) and actinium-225, produced from radium-226 targets via a linac-driven route; the company reported shipping Ac-225 product to customers from 2021 and targeted 1-2 mCi/week production by 2022. Niowave also has an active molybdenum-99 programme using low-enriched uranium targets processed through a uranium target assembly (UTA), pursued in part under a NNSA cooperative agreement and reviewed through NRC pre-application meetings, aiming at commercial-scale, reactor-independent Mo-99/Tc-99m supply for North America.\n\nNiowave's linac technology can in principle also produce other beta- and alpha-emitting fission fragments and activation products (for example copper-67, yttrium-90, and various rare-earth isotopes) as a byproduct of its uranium fission-based programme, positioning it as an alternative, non-reactor node in the therapeutic isotope supply chain alongside reactor-based (Lu-177, Mo-99) and cyclotron-based (Ac-225, At-211) producers.","status":"active","asOf":"2026-09-22","links":[{"label":"OSTI: Niowave DOE-NP SBIR Phase II final technical report, superconducting electron linac for radioisotope production","url":"https://www.osti.gov/servlets/purl/1209691"},{"label":"NRC: Niowave public meeting presentation, domestic production of Mo-99 and other fission products without a nuclear reactor (2021)","url":"https://www.nrc.gov/docs/ML2135/ML21356B719.pdf"},{"label":"NRC: Niowave pre-application meeting #2 slides (2022)","url":"https://www.nrc.gov/docs/ML2212/ML22129A075.pdf"},{"label":"JACoW/NAPAC 2019: High-power superconducting electron linacs for commercial applications (Niowave)","url":"https://proceedings.jacow.org/napac2019/talks/wezbb4_talk.pdf"}],"tags":["superconducting linac","actinium-225","molybdenum-99","isotope production"],"related":["actinium-225-supply","research-reactor-isotope-production","therapy-isotope-supply-chain","tc-99m","mo-99","lu-177","ac-225","y-90","at-211","cu-67"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Lansing, Michigan, US","country":"US","companyType":"radiopharma","website":"https://niowaveinc.com","founded":2005,"stage":"private-large","investors":[],"funding":[],"route":"/companies/niowave/"}
{"id":"bwxt-medical","kind":"company","name":"BWXT Medical","aka":["BWXT Medical Ltd."],"tldr":"A Canadian company, owned by the US nuclear firm BWXT, that is building a made-in-Canada supply of the technetium generators hospitals use for the vast majority of nuclear medicine scans, plus other isotopes and radiotherapy hardware.","summary":"BWXT Medical Ltd. is the nuclear medicine subsidiary of BWX Technologies, Inc. (NYSE: BWXT), operating manufacturing and processing facilities in Ottawa and Vancouver, Canada. Its central programme is a proprietary route to molybdenum-99 (Mo-99), the parent isotope of technetium-99m (Tc-99m), the radionuclide used in roughly 80% of nuclear medicine procedures worldwide. Rather than irradiating enriched-uranium targets in a research reactor, BWXT's approach irradiates natural molybdenum targets in an operating commercial power reactor: since 2018/2019 it has worked with Ontario Power Generation and its subsidiary Laurentis Energy Partners to install a Target Delivery System (TDS) at OPG's Darlington Nuclear Generating Station, making Darlington the first commercial power reactor in the world to produce Mo-99. The Mo-99 is processed at BWXT Medical's Ottawa facility into proprietary Tc-99m generators intended as drop-in replacements for existing hospital and radiopharmacy generators, pending FDA and Health Canada approval; a February 2023 milestone confirmed installation and initial commissioning of the isotope system at Darlington.\n\nBWXT Medical's isotope portfolio extends beyond Mo-99/Tc-99m: industry directory material describes it as also handling actinium-225, indium-111, iodine-123, strontium-82 and germanium-68, and as pursuing cobalt-60 production at Darlington (alongside existing extraction at OPG's Pickering station). The company is also the exclusive contract manufacturer, outside China, of TheraSphere (yttrium-90 glass microspheres for radioembolisation) in partnership with Boston Scientific, and has worked with Laurentis on scalable production infrastructure at Darlington intended to support lutetium-177 as well as Mo-99.\n\nAs a large, reactor-adjacent contract manufacturer, BWXT Medical sits in the therapeutic and diagnostic isotope supply chain alongside other Mo-99/Tc-99m producers (Curium, NTP Radioisotopes, ANSTO) and complements Boston Scientific's radioembolisation device business through its TheraSphere manufacturing role.","status":"active","asOf":"2026-09-22","links":[{"label":"BWXT Medical: BWXT Medical and Laurentis complete key Tc-99m generator program milestone (2023)","url":"https://www.bwxtmedical.com/bwxt-medical-and-laurentis-complete-key-tc-99m-generator-program-milestone/"},{"label":"BWXT Medical: Tc-99m generators product sheet (PDF)","url":"https://bwxtmedical.com/wp-content/uploads/2024/05/tc-99m-product-sheet.pdf"},{"label":"BWXT Medical: BWXT Names Nuclear Medicine Business as BWXT Medical (2021)","url":"https://www.bwxtmedical.com/bwxt-names-nuclear-medicine-business-as-bwxt-medical/"},{"label":"BWXT/OPG: OPG and BWXT make significant progress in production of Mo-99 at Darlington (2020)","url":"https://www.bwxt.com/opg-and-bwxt-make-significant-progress-in-production-of-life-saving-medical-isotope-at-darlington-nuclear-generating-station-2/"},{"label":"CNIC: Canadian Isotope Ecosystem Directory 2025 (BWXT Medical entry, PDF)","url":"https://s45591.pcdn.co/wp-content/uploads/2025/12/2025-CNIC-Medical-Isotope-Ecosystem-Directory-DEC2025-AX.pdf"}],"tags":["molybdenum-99","technetium-99m","generator","radioembolisation"],"related":["research-reactor-isotope-production","radioembolisation-tare","boston-scientific","therapy-isotope-supply-chain","tc-99m","i-123","in-111","mo-99","ge-68","lu-177","ac-225","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Ottawa, Ontario, Canada","country":"CA","companyType":"radiopharma","website":"https://www.bwxtmedical.com","stage":"acquired","investors":[],"funding":[],"route":"/companies/bwxt-medical/"}
{"id":"quirem-medical","kind":"company","name":"Quirem Medical","aka":["Quirem Medical B.V."],"tldr":"A Dutch company, owned by Terumo, that makes tiny radioactive beads containing holmium-166 which are injected into the liver's blood vessels to irradiate liver tumours from the inside, plus the imaging tools used to plan and check that treatment.","summary":"Quirem Medical B.V. is a Netherlands-based medical device company, spun out of University Medical Centre Utrecht (UMCU) after roughly two decades of academic development of holmium-166 microsphere technology. It develops and manufactures the Holmium Platform for selective internal radiation therapy (SIRT, also called radioembolisation) of liver tumours: QuiremSpheres (therapeutic holmium-166 microspheres), QuiremScout (a low-activity holmium-166 scout dose used for pre-treatment work-up in place of 99mTc-MAA), and Q-Suite (dosimetry planning and verification software). QuiremSpheres are, per the company, the only commercially available SIRT microspheres containing holmium-166 rather than yttrium-90, a property that allows them to be visualised and quantified by both SPECT and MRI even at low concentrations, which the company says supports more accurate patient selection, dose planning and post-treatment dose verification than yttrium-90-based competitor products.\n\nTerumo Corporation first invested in Quirem in 2015 and became its exclusive global distributor, then acquired an 80.1% stake (taking full ownership) in July 2020 for an upfront $20 million plus up to $25 million in milestone payments through 2030, folding Quirem into Terumo's interventional oncology portfolio. The full Holmium Platform is CE-marked and available across Europe, the Middle East and Africa; in the UK, NICE recommended QuiremSpheres for hepatocellular carcinoma patients with Child-Pugh A liver function when conventional transarterial therapies are inappropriate (2024), triggering NHS reimbursement. Clinical evidence includes the HEPAR Primary study (published Journal of Nuclear Medicine, 2022), which reported a 54% objective response rate at three months in unresectable HCC patients (BCLC stage B and C) without curative options, and the earlier HEPAR dose-escalation study (Lancet Oncology, 2012) supporting safety and efficacy in chemorefractory liver metastases.\n\nQuirem sits in the radioembolisation supply chain as a smaller, differentiated challenger to the market-leading yttrium-90 microsphere products (Sirtex's SIR-Spheres, Boston Scientific's TheraSphere), competing on the imaging and dosimetry advantages of holmium-166 rather than on scale.","status":"active","asOf":"2026-09-22","links":[{"label":"Terumo: Terumo Acquires Quirem Medical to Enhance its Interventional Oncology Portfolio (2020)","url":"https://www.terumo.com/newsrelease/detail/20200715/543"},{"label":"Terumo: NICE publishes new guidance supporting QuiremSpheres for HCC (2024)","url":"https://www.terumo.com/newsrelease/detail/20240703/6221"},{"label":"Terumo: Holmium-166 SIRT demonstrates safety and efficacy in HEPAR Primary study (JNM 2022) (2022)","url":"https://www.terumo.com/newsrelease/detail/20220614/5296"},{"label":"Terumo: Terumo and Quirem welcome positive reimbursement decision for QuiremSpheres in the Netherlands (2018)","url":"https://www.terumo.com/newsrelease/detail/20180412/274"},{"label":"Quirem: administration procedure manual (PDF)","url":"https://www.quirem.com/wp-content/uploads/2022/10/LC-8007204-Administration-Procedure-Manual.pdf"}],"tags":["holmium-166","radioembolisation","liver cancer","SIRT"],"related":["radioembolisation-tare","hcc","hcc-intermediate","sirtex","boston-scientific","spect","tare","tc-99m","y-90","ho-166"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Deventer, the Netherlands","country":"NL","companyType":"radiopharma","website":"https://www.quirem.com","stage":"acquired","investors":[],"funding":[],"route":"/companies/quirem-medical/"}
{"id":"oncobeta","kind":"company","name":"OncoBeta","aka":["OncoBeta GmbH","OncoBeta International"],"tldr":"A German medical device company that makes a skin-patch radiotherapy for early skin cancer: a paste containing a radioactive isotope, rhenium-188, is applied over the tumour for under three hours instead of surgery.","summary":"OncoBeta GmbH, headquartered near Munich, Germany, is a privately held medical device and radiochemical company specialising in epidermal (skin-surface) radioisotope therapy for non-melanoma skin cancer (NMSC). Its product, Rhenium-SCT (Skin Cancer Therapy), applies a paste containing the beta-emitting radioisotope rhenium-188, embedded in a resin matrix, to basal cell carcinoma, squamous cell carcinoma and Bowen's disease lesions via an adhesive protective film; beta particles deposit about 92% of their energy within roughly 3 mm of depth, sparing underlying tissue, in a single outpatient session typically lasting 45-180 minutes depending on lesion size and depth (target dose around 50 Gy). No surgical incision is required and the company reports patients can resume normal activity once the film and dried paste are removed.\n\nRhenium-SCT has been CE-certified since 2014 and holds additional device registrations in Australia (ARTG), Spain, New Zealand and Singapore. The rhenium-188 itself is produced on demand from a tungsten-188/rhenium-188 generator, sold separately by OncoBeta to hospitals and nuclear medicine facilities (available up to 55.5 GBq/1.5 Ci of 188W, not for direct human use in that form), decoupling clinics from having to source the isotope from external radiopharmacies.\n\nClinical evidence includes a long-term retrospective study (2005-2014 cohort, 55 lesions) reporting complete remission in all treated lesions with no reported complications, and the ongoing international, multicentre EPIC-Skin Phase IV study; a 12-month interim analysis across sites in Australia, Austria, Germany, the UK and South Africa (184 patients, 254 lesions) reported an overall response rate of 97.3% and complete response rate of 94.1% (94.1% BCC / 94.2% SCC, per OncoBeta's own 12-month clinical paper), favourable quality-of-life and cosmetic outcomes, no reported pain during treatment, and no Grade 3 or 4 toxicities at 12 months (Grade 2 toxicity in 6.9%). OncoBeta positions Rhenium-SCT as an alternative to surgery for patients where excision carries cosmetic or comorbidity concerns, particularly for lesions on the face, scalp or other cosmetically sensitive sites.","status":"active","asOf":"2026-09-22","links":[{"label":"OncoBeta: technology overview (Rhenium-SCT, 188W/188Re generator)","url":"https://www.oncobeta.com/technology/"},{"label":"OncoBeta: 12-month results from international Phase IV EPIC-Skin study (2026)","url":"https://www.oncobeta.com/media/oncobeta-reports-12-month-results-from-international-phase-iv-study-for-non-melanoma-skin-cancer/"},{"label":"OncoBeta Australia: EPIC-Skin 12-month study clinical paper (PDF)","url":"https://www.oncobeta.com.au/wp-content/uploads/2025/07/EPIC-Skin-12-Month-Study-Clinical-Paper_Digital_v7-2-1.pdf"},{"label":"OncoBeta: personalized irradiation therapy for NMSC by Rhenium-188 skin cancer therapy, long-term retrospective study","url":"https://www.oncobeta.com/company/details/personalized-irradiation-therapy-for-nmsc-by-rhenium-188-skin-cancer-therapy-a-long-term-retrospective-study"},{"label":"OncoBeta: patients / step-by-step treatment guide","url":"https://www.oncobeta.com/patients/"}],"tags":["rhenium-188","skin cancer","epidermal brachytherapy","beta emitter"],"related":["radionuclide-generators-kits","re-188"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Garching, Germany (near Munich)","country":"DE","companyType":"devices","website":"https://www.oncobeta.com","stage":"private-large","investors":[],"funding":[],"route":"/companies/oncobeta/"}
{"id":"alpha-tau-medical","kind":"company","name":"Alpha Tau Medical","aka":["Alpha Tau","DRTS"],"tldr":"An Israeli company that places tiny radioactive seeds directly inside a solid tumour; the seeds release a burst of highly damaging particles that mostly stay within a few millimetres of the tumour, sparing surrounding healthy tissue.","summary":"Alpha Tau Medical Ltd. (Nasdaq: DRTS, DRTSW), founded in 2016 and headquartered in Jerusalem, develops Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy), a device-like intratumoural radiotherapeutic technology originally developed by Prof. Itzhak Kelson and Prof. Yona Keisari at Tel Aviv University. Thin wire sources impregnated with radium-224 are inserted directly into a solid tumour; as the radium decays through a chain of short-lived daughter isotopes, high-energy alpha particles are released and diffuse a short distance (up to roughly 2.5 mm) into surrounding tissue. Because tumour vasculature tends to trap the diffusing daughter atoms while organised healthy tissue clears them, the company designs the sources to concentrate alpha-particle damage within the tumour and its immediate margin rather than delivering systemic or wide-field radiation.\n\nAlpha DaRT has not yet received full regulatory approval for routine clinical use in the countries it operates in (the US, Canada, Europe and Israel) and remains investigational, but is in multiple clinical trials spanning skin, head and neck, pancreatic, lung, prostate and brain tumours. Reported data include a pooled first-in-human analysis in pancreatic ductal adenocarcinoma (100% local disease control in evaluable patients, presented at Digestive Disease Week 2026) and an interim analysis of Alpha DaRT combined with pembrolizumab in recurrent, inoperable head and neck cancer (75% objective response rate, 37.5% complete response in the first eight patients, unpublished as of the company's reporting). The company completed enrolment of its IMPACT pilot study (48 patients, US/Canada/Israel) combining Alpha DaRT with first-line chemotherapy in unresectable or metastatic pancreatic adenocarcinoma in August 2026, with initial data expected in early 2027 (ClinicalTrials.gov NCT06698458).\n\nIn 2026 Alpha Tau announced a strategic collaboration with Tolmar to develop and commercialise Alpha DaRT for prostate cancer in the United States, including a $20 million equity investment at a 25% premium, $15 million toward expanded US manufacturing, and up to $161.5 million in development, regulatory and commercial milestones for the first indication, plus an ongoing supply agreement. Alpha Tau secured a radioactive materials licence for its first commercial-scale Alpha DaRT manufacturing facility in Hudson, New Hampshire, in October 2025, with a first-phase nameplate capacity of roughly 400,000 sources.","status":"active","asOf":"2026-09-22","links":[{"label":"Alpha Tau: Q2 2026 financial results and corporate update","url":"https://alphatau.com/alpha-tau-announces-second-quarter-2026-financial-results-and-provides-corporate-update/"},{"label":"Alpha Tau: Alpha DaRT technology overview","url":"https://alphatau.com/alpha-dart-technology/"},{"label":"Alpha Tau: 100% local disease control rate in Alpha DaRT pancreatic cancer trials, presented at DDW 2026","url":"https://alphatau.com/alpha-tau-announces-100-local-disease-control-rate-and-favorable-safety-profile-observed-in-alpha-dart-pancreatic-cancer-trials-presented-at-ddw-2026/"},{"label":"Alpha Tau: receipt of radioactive material license for New Hampshire manufacturing facility (2025)","url":"https://www.globenewswire.com/news-release/2025/10/21/3170190/0/en/alpha-tau-announces-receipt-of-radioactive-material-license-for-its-new-hampshire-manufacturing-facility-advancing-towards-commercial-readiness.html"},{"label":"GlobeNewswire (via Manila Times): Alpha Tau completes enrollment in IMPACT pancreatic cancer pilot study (2026)","url":"https://www.manilatimes.net/2026/08/31/tmt-newswire/globenewswire/alpha-tau-completes-patient-enrollment-in-its-multicenter-impact-pancreatic-cancer-pilot-study-of-alpha-dart-following-strong-demand-and-multiple-expansions/2415115"}],"tags":["radium-224","intratumoural alpha therapy","alpha emitter","solid tumours"],"related":["targeted-alpha-therapy","prostate","pembrolizumab","ra-224"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Jerusalem, Israel","country":"IL","companyType":"radiopharma","website":"https://alphatau.com","ticker":"NASDAQ: DRTS","founded":2016,"stage":"public","investors":[],"funding":[],"route":"/companies/alpha-tau-medical/"}
{"id":"nuclidium","kind":"company","name":"Nuclidium","aka":["Nuclidium AG"],"tldr":"A Swiss biotech using two forms of radioactive copper, one for scanning and one for treatment, joined to the same targeting molecule so the same drug design can both find and then destroy a tumour.","summary":"Nuclidium AG is a clinical-stage biotechnology company headquartered in Basel, Switzerland (with an additional site in Munich, Germany), founded in 2017 to develop copper-based radiopharmaceutical theranostics. Its CuTrace platform pairs copper-61 (a positron emitter used for diagnostic PET imaging) with copper-67 (a beta emitter used for therapy) on the same chelator and targeting ligand, so that the diagnostic and therapeutic doses use the same radiometal chemistry rather than switching between different metals (for example gallium-68/lutetium-177) as most current theranostic pairs do.\n\nIts lead programme, NU101, targets PSMA for metastatic castration-resistant prostate cancer: the 61Cu-labelled diagnostic component is designed to allow delayed imaging time points, which the company says can improve detection of very small metastases, while the 67Cu-labelled therapeutic component is intended to deliver targeted radiation with an improved safety and efficacy profile at reduced radiation burden relative to existing options. In January 2026, Nuclidium announced issuance of US Patent No. 12,527,885 covering its 61Cu-based radiodiagnostic programme for PSMA-positive prostate cancer, reinforcing its intellectual-property position in copper-61 PSMA imaging.\n\nNuclidium's copper-based approach places it in competition with other copper theranostic developers using different copper isotope pairs and chelator chemistry, notably Clarity Pharmaceuticals' SAR-bisPSMA programme, which pairs copper-64 (diagnostic) with copper-67 (therapeutic) using a distinct sarcophagine cage chelator; the two companies represent parallel but chemically different bets on copper radiometals as an alternative to the established gallium/lutetium and fluorine/actinium theranostic pairs.","status":"active","asOf":"2026-09-22","links":[{"label":"Nuclidium: company site","url":"https://nuclidium.com/"},{"label":"Nuclidium: pipeline (NU101)","url":"https://nuclidium.com/pipeline/"},{"label":"Nuclidium: issuance of new US patent covering its 61Cu-based radiodiagnostic programme for PSMA-positive prostate cancer (2026)","url":"https://nuclidium.com/nuclidium-announces-issuance-of-new-u-s-patent-covering-its-61cu-based-radiodiagnostic-program-for-psma-positive-prostate-cancer/"}],"tags":["copper-61","copper-67","theranostics","PSMA"],"related":["psma","prostate-mcrpc","clarity-pharmaceuticals","ga-68","cu-64","lu-177","cu-67"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Basel, Switzerland","country":"CH","companyType":"radiopharma","website":"https://nuclidium.com","founded":2017,"stage":"growth","investors":[],"funding":[],"route":"/companies/nuclidium/"}
{"id":"full-life-technologies","kind":"company","name":"Full-Life Technologies","aka":["Full-Life"],"tldr":"A radiopharmaceutical drug developer with sites in Europe and China that designs its own targeting molecules and pairs them with radioactive actinium or lutetium; its biggest programme, for a receptor found on several solid tumour types, has been licensed to a Korean partner in a deal worth up to $571.5 million.","summary":"Full-Life Technologies is a fully integrated, clinical-stage global radiotherapeutics company founded in 2021, with operations spanning Belgium, Germany and China (Heidelberg, Germany and Chengdu, China both appear in its own press materials as operating hubs). It is built around an internal discovery platform, described in its own materials as UniRDC, for identifying and optimising small-molecule radionuclide drug conjugates (RDCs) against solid-tumour targets, and around building its own radioisotope production and logistics capability rather than relying solely on external isotope suppliers.\n\nIts most advanced disclosed asset is FL-091 (also referred to as 177Lu-FL-091 and 225Ac-FL-091), a small-molecule radioligand targeting neurotensin receptor 1 (NTSR1), which is overexpressed in colorectal, breast, pancreatic and head-and-neck cancers among others. In July 2024, Full-Life licensed exclusive worldwide clinical development, manufacturing and commercialisation rights to FL-091 to SK Biopharmaceuticals in a deal valued at up to $571.5 million (upfront payment plus development and commercial milestones, excluding royalties). SK Biopharmaceuticals renamed the compound SKL35501 (therapeutic, actinium-225-based) and SKL35502 (imaging companion), and announced FDA IND approval for a first-in-human Phase 1 study in January 2026, with the same dossier submitted to Korea's Ministry of Food and Drug Safety for concurrent US/Korea development in patients with NTSR1-expressing advanced solid tumours who have failed or relapsed on standard treatment.\n\nFull-Life's own pipeline, retained independently of the SK deal, includes 225Ac-FL-020, an actinium-225-based PSMA-targeting RDC in early clinical development for metastatic castration-resistant prostate cancer, and FL-261, a c-MET-targeted theranostic RDC programme for multiple solid tumours. The company closed a $150 million Series D financing package in May 2026 (roughly $110 million equity, $40 million debt) led by Vivo Capital with participation from SK Biopharmaceuticals, taking cumulative funding to nearly $350 million since 2021; it has also built a manufacturing facility in Gembloux, Belgium, which completed construction in August 2026 and began accelerator commissioning.","status":"active","asOf":"2026-09-22","links":[{"label":"Full-Life: Full-Life Technologies, SK Biopharmaceuticals enter $571.5M licence agreement for FL-091 (2024)","url":"https://www.full-life.com/media/press-releases/28"},{"label":"Full-Life: SK Biopharmaceuticals receives FDA IND approval for alpha-emitter-based radiopharmaceutical therapy (SKL35501) (2026)","url":"https://www.full-life.com/media/press-releases/42"},{"label":"FierceBiotech: SK inks $572M deal for Full-Life radiopharma prospect (2024)","url":"https://www.fiercebiotech.com/biotech/sk-inks-572m-deal-full-life-prospect-advancing-push-become-asias-radiopharma-leader"},{"label":"Full-Life: development of 177Lu-FL-091 for NTSR1-positive cancers (2024)","url":"https://www.full-life.com/media/press-releases/26"},{"label":"wewillcure.com: 10 biotech companies advancing radiopharmaceutical treatments (Full-Life financial/pipeline summary)","url":"https://wewillcure.com/insights/company-profiles/oncology/biotech-companies-advancing-radiopharmaceutical-treatments"}],"tags":["actinium-225","neurotensin receptor 1","radionuclide drug conjugate"],"related":["psma","prostate-mcrpc","targeted-alpha-therapy","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"Heidelberg, Germany (also Chengdu, China; Gembloux, Belgium manufacturing)","country":"DE","companyType":"radiopharma","website":"https://www.full-life.com","founded":2021,"stage":"growth","investors":[],"funding":[],"route":"/companies/full-life-technologies/"}
{"id":"molecular-targeting-technologies","kind":"company","name":"Molecular Targeting Technologies","aka":["MTTI","Molecular Targeting Technologies, Inc."],"tldr":"A Pennsylvania biotech that adds a chemical 'handle' to existing radioactive cancer drugs so the drug binds briefly to albumin, the body's most abundant blood protein, letting it linger in the tumour for days on a fraction of the usual radiation dose.","summary":"Molecular Targeting Technologies, Inc. (MTTI) is a clinical-stage biotechnology company headquartered in West Chester, Pennsylvania. Its central asset is EvaThera, a target-agnostic pharmacokinetic engineering platform based on Evans Blue-mediated reversible albumin binding: an Evans Blue-derived moiety is attached to an existing targeting ligand and chelator, so that after the radioligand binds its target it also transiently binds circulating albumin, extending its circulation time, increasing tumour exposure and prolonging tumour retention without requiring discovery of a new molecular target.\n\nThe platform's lead clinical application is 177Lu-DOTA-EB-TATE (EBTATE), an albumin-binding somatostatin receptor 2 (SSTR2)-targeted radiopharmaceutical for gastroenteropancreatic neuroendocrine tumours (GEP-NETs), originally developed and licensed from the US National Institutes of Health; MTTI is advancing it toward pivotal Phase III development, with US trials stated to have begun at Memorial Sloan Kettering Cancer Center. Clinical experience with EBTATE reported by the company across 81 patients found tumour retention for up to 15 days, roughly eight-fold higher tumour uptake and/or retention compared with 177Lu-DOTA-TATE (Lutathera's active ingredient), a 50% objective response rate, 100% disease control rate, 36-month median progression-free survival, no observed kidney toxicity through one year of follow-up, and clinical activity achieved using only about 12.5% of the cumulative radioactivity used in conventional four-cycle PRRT (data presented at SNMMI 2026 and the 2026 Targeted Radiopharmaceuticals Summit; not yet FDA-approved).\n\nMTTI is extending EvaThera beyond SSTR2 to additional programmes including EB-RGD (integrin alphaVbeta3, aimed at glioblastoma and non-small-cell lung cancer), EB-FAPI (fibroblast activation protein) and EB-GRPR (gastrin-releasing peptide receptor), using both lutetium-177 and actinium-225 (225Ac-EBTATE, being developed for small-cell lung cancer, reported preclinically comparable to 225Ac-DOTATATE at roughly 40% of the administered dose). In 2026, Pharma Tech Outlook named EvaThera its Radiopharmaceutical Therapy Solution of the Year, and MTTI describes itself as actively seeking licensing and co-development partnerships to apply EvaThera to third-party radiopharmaceutical programmes.","status":"active","asOf":"2026-09-22","links":[{"label":"BioSpace: Molecular Targeting Technologies receives Pharma Tech Outlook's 2026 Radiopharmaceutical Therapy Solution of the Year award for EvaThera","url":"https://www.biospace.com/press-releases/molecular-targeting-technologies-receives-pharma-tech-outlooks-2026-radiopharmaceutical-therapy-solution-of-the-year-award-for-evathera"},{"label":"MyChesCo: West Chester biotech targets radiopharma partnerships (2026)","url":"https://www.mychesco.com/a/news/business/west-chester-biotech-targets-radiopharma-partnerships/"},{"label":"Business Wire: MTTI highlights clinical experience in 81 GEP-NETs patients and differentiated profile of EBTATE, following presentation at SNMMI 2026","url":"https://www.businesswire.com/news/home/20260610511667/en/MTTI-Highlights-Clinical-Experience-in-81-GEP-NETs-Patients-and-Differentiated-Profile-of-Next-Generation-PRRT-Candidate-EBTATE-Following-Presentation-at-SNMMI-2026"},{"label":"Business Wire: Molecular Targeting Technologies presents first clinical validation of the Evans Blue platform (2026)","url":"https://www.businesswire.com/news/home/20260707936626/en/Molecular-Targeting-Technologies-Presents-First-Clinical-Validation-of-the-Evans-Blue-Platform-Demonstrating-Up-to-15-Day-Tumor-Retention-Using-Approximately-12.5-of-the-Radioactivity-Required-for-Conventional-PRRT"}],"tags":["albumin binding","PRRT","EvaThera","lutetium-177","actinium-225"],"related":["sstr2","neuroendocrine","small-intestinal-net","pancreatic-net","lutathera","prrt","fap","sclc","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hq":"West Chester, Pennsylvania, US","country":"US","companyType":"biotech","website":"https://www.mtarget.com","founded":1995,"stage":"private-large","investors":[],"funding":[],"route":"/companies/molecular-targeting-technologies/"}
{"id":"f-molecular-imaging","kind":"section","name":"Molecular imaging","aka":[],"tldr":"Molecular imaging uses a small radioactive tracer injected into the body and a PET or SPECT camera to show where a specific protein sits on a tumour, so doctors can pick the right treatment and check it is working.","summary":"Molecular imaging is the diagnostic half of theranostics: a radiolabelled ligand binds a target expressed on tumour cells (PSMA, SSTR2, FAP, HER2, CAIX, TROP2 and others) and a PET/CT or PET/MRI camera maps its distribution across the whole body. The field's biggest single deployment is PSMA PET in prostate cancer: the joint EANM/SNMMI PSMA PET/CT procedure guideline 2.0 (Fendler et al., Eur J Nucl Med Mol Imaging 2023) and the 2026 NCCN guidelines now recommend PSMA PET ahead of conventional imaging for unfavourable intermediate- and high-risk staging and for biochemical recurrence, and require it to select patients for PSMA-targeted radioligand therapy. The 2020 proPSMA trial (Hofman et al., Lancet) established the head-to-head case against CT and bone scan.\n\nSomatostatin receptor (SSTR) PET with 68Ga-DOTATATE or DOTATOC plays the equivalent gatekeeping role for peptide receptor radionuclide therapy in neuroendocrine tumours, and FAPI PET is being explored as a pan-cancer stromal imaging agent, though it does not yet have the guideline weight of PSMA or SSTR PET. FDG PET remains the workhorse general-oncology tracer and the comparator against which every newer agent is judged.\n\nWhat is unsolved in 2026: PSMA expression is heterogeneous and a meaningful fraction of mCRPC patients are PSMA-negative or discordant on biopsy, so imaging-based patient selection is an imperfect proxy for radioligand therapy response; quantitative reporting (SUV, PROMISE/miTNM, E-PSMA) is still not uniformly applied across sites; and reimbursement for newer PET tracers lags their guideline recommendation in several health systems. Total-body PET and AI-assisted reading are being investigated to cut dose and scan time but are not yet standard of care.","asOf":"2026-09-22","links":[{"label":"EANM/SNMMI: PSMA PET/CT procedure guideline 2.0 (Eur J Nucl Med Mol Imaging, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10027805/"},{"label":"proPSMA trial (Hofman et al., Lancet 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/"},{"label":"PMC: Future opportunities and nuances with PSMA PET (2026 review, incl. 2026 NCCN guidance)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13141699/"}],"tags":[],"related":["f-radioligand-therapy","f-dosimetry","ga-68"],"indications":["prostate","prostate-bcr","prostate-high-risk","neuroendocrine","rcc"],"sections":[],"technologies":["psma-pet","sstr-pet","fdg-pet","fapi-pet","pet-ct","pet-mri","immuno-pet","caix-pet","her2-pet","trop2-pet","quantitative-imaging-biomarkers","total-body-pet-screening"],"targets":[],"drugs":["ga68-psma-11","pylarify","flotufolastat","psma-1007-f18","ga68-dotatate","fludeoxyglucose-f18","girentuximab-zr89","fluoroestradiol-f18","illuccix","locametz"],"companies":["telix","lantheus","curium","blue-earth-diagnostics","novartis","ge-healthcare","siemens-healthineers","united-imaging","isotopia","sofie-biosciences"],"institutions":[],"pathways":[],"terms":["suv","theranostics"],"trials":["propsma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["PSMA-negative or discordant disease on biopsy is not resolved by better tracers alone; it is a biology problem, not a chemistry one.","Quantitative reporting frameworks (PROMISE/miTNM, E-PSMA) exist but adoption across sites is uneven, which limits cross-trial comparability.","Reimbursement for newer PET agents (e.g. flotufolastat, PSMA-1007) trails clinical guideline endorsement in several countries."],"order":1,"route":"/fronts/f-molecular-imaging/"}
{"id":"f-radioligand-therapy","kind":"section","name":"Radioligand therapy","aka":[],"tldr":"Radioligand therapy attaches a radioactive particle to a molecule that homes in on a tumour, so the radiation is delivered from the inside of the cancer rather than from an external beam.","summary":"Radioligand therapy (RLT) with beta-emitters is the most clinically mature branch of theranostics. Lutetium-177 vipivotide tetraxetan (Pluvicto, 177Lu-PSMA-617) is approved by the FDA and EMA for PSMA-positive metastatic castration-resistant prostate cancer, on the strength of the VISION trial (median overall survival 15.3 vs 11.3 months, HR 0.62; radiographic progression-free survival 8.7 vs 3.4 months, HR 0.40; Sartor et al., NEJM 2021) and the earlier-line PSMAfore trial (rPFS 9.3 vs 5.6 months, HR 0.41), which supported the FDA's March 2025 label expansion into taxane-naive mCRPC. Lutetium-177 dotatate (Lutathera) is approved for gastroenteropancreatic neuroendocrine tumours on the basis of NETTER-1 (Strosberg et al., NEJM 2017) and has since been extended to a first-line setting by NETTER-2 (Lancet 2024).\n\nA competitive multi-agent PSMA-RLT field is emerging behind Pluvicto: 177Lu-PSMA-I&T (PNT2002, Lantheus/POINT Biopharma) reported the SPLASH trial, and Telix's antibody-based rosopatamab tetraxetan (TLX591-Tx) is in the ProstACT Global phase 3 programme. On the neuroendocrine side, 177Lu-edotreotide (ITM-11) and FAP-targeted 177Lu-FAP-2286 are in later-phase development.\n\nWhat remains unsolved: a 2026 GRADE-assessed meta-analysis of six randomised trials (Mubarika et al., Int Urol Nephrol 2026) found the primary intention-to-treat overall-survival benefit of 177Lu-PSMA over standard of care was not statistically significant (HR 0.81, 95% CI 0.62-1.06), with a benefit only apparent after adjusting for control-arm crossover (HR 0.76, 95% CI 0.59-0.96) — a reminder that trial-design choices, not just the isotope, drive the reported benefit. Optimal sequencing against androgen-receptor pathway inhibitors, taxanes and alpha emitters is still being worked out in trials such as PSMAddition and ENZA-p, and lutetium-177's roughly 0.5-2 mm beta path length is thought to undertreat isolated tumour cells and micrometastases, motivating the move to alpha emitters.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto (accessdata.fda.gov)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf"},{"label":"VISION trial (Sartor et al., NEJM 2021)","url":"https://www.nejm.org/doi/10.1056/NEJMoa2107322"},{"label":"GRADE-assessed meta-analysis of 177Lu-PSMA RCTs (Int Urol Nephrol, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/42570199/"},{"label":"Guideline of guidelines: 177Lu-PSMA RLT (BJU Int, 2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13458634/"}],"tags":[],"related":["f-molecular-imaging","f-alpha-therapy","f-dosimetry","lu-177"],"indications":["prostate-mcrpc","prostate-mhspc","neuroendocrine","small-intestinal-net","pancreatic-net","lung-net"],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy","prrt","peptide-drug-conjugate","psma-pet","sstr-pet"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it","itm-11","fap-2286"],"companies":["novartis","advanced-accelerator-applications","point-biopharma","lantheus","itm","telix"],"institutions":[],"pathways":[],"terms":["prrt-term","psa50","mcrpc-mhspc"],"trials":["vision","psmafore","netter-1","splash","psmaddition"],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021","paper-netter-1-nejm-2017","paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":["A 2026 GRADE meta-analysis found the ITT overall-survival benefit of 177Lu-PSMA vs standard of care was not significant (HR 0.81, 95% CI 0.62-1.06) until adjusted for crossover (HR 0.76, 95% CI 0.59-0.96); trial design materially changes the reported effect size.","Optimal sequencing of RLT against ARPIs, taxanes and alpha emitters is unresolved; PSMAddition and ENZA-p are testing earlier and combined use.","177Lu's beta path length (roughly 0.5-2 mm) is thought to leave isolated tumour cells and micrometastases undertreated, which is the main argument for moving to alpha emitters."],"order":2,"route":"/fronts/f-radioligand-therapy/"}
{"id":"f-alpha-therapy","kind":"section","name":"Targeted alpha therapy","aka":[],"tldr":"Alpha therapy uses a heavier type of radioactive particle that travels only a few cell widths but hits much harder, aimed at cancer cells that have stopped responding to the gentler beta-particle treatments.","summary":"Targeted alpha therapy (TAT) conjugates an alpha-emitting radionuclide, most often actinium-225, to the same PSMA or somatostatin-receptor ligands used in beta radioligand therapy. Alpha particles have a short tissue range (tens of micrometres, a few cell diameters) but a much higher linear energy transfer than beta particles, so they cause dense, largely non-repairable double-strand DNA breaks. Radium-223 (Alpharadin), an alpha-emitting bone-seeking agent, was the first alpha emitter approved in oncology, on the basis of the ALSYMPCA trial (improved overall survival and delayed skeletal-related events in bone-predominant mCRPC).\n\nFor tumour-targeted alpha therapy, 225Ac-PSMA agents (including Fusion Pharmaceuticals' FPI-2265 in the AlphaBreak programme, and RayzeBio/BMS's RYZ101, 225Ac-DOTATATE, for neuroendocrine tumours) are in phase 1/2 development, largely in patients who progressed on or are refractory to lutetium-177 therapy. A 2026 systematic review and meta-analysis (Belabaci et al., Eur J Nucl Med Mol Imaging 2026) assessed combined 225Ac/177Lu-PSMA therapy but the field still lacks randomised phase 3 evidence for any alpha-PSMA agent.\n\nThe defining unsolved problem is supply, not biology: global 225Ac production is estimated at roughly 63 GBq (1.7 Ci) per year, sufficient for only about 100-200 patients annually, against an estimated clinical and trial demand of around 185 GBq/year and rising (Alpha Atlas / IAEA TECDOC-2057, 2024). Production depends on a handful of 229Th generators (Oak Ridge National Laboratory, the EU Joint Research Centre in Karlsruhe, and Russia's IPPE) or on cyclotron irradiation of 226Ra, and the IAEA's Global Radium-226 Management Initiative is recovering legacy radium sources from around 80 countries as an alternative feedstock. Xerostomia (salivary gland uptake) and dosimetric uncertainty are the main clinical limitations reported so far.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC-2057: Production and quality control of actinium-225 radiopharmaceuticals (2024)","url":"https://www-pub.iaea.org/MTCD/publications/PDF/TE-2057web.pdf"},{"label":"ALSYMPCA trial (Parker et al., NEJM 2013)","url":"https://www.nejm.org/doi/10.1056/NEJMoa1213755"},{"label":"IAEA: Global Radium-226 Management Initiative update (ANS, Jan 2026)","url":"https://www.ans.org/news/2026-01-14/article-7675/iaeas-global-radium226-management-initiative-continues-to-progress/"},{"label":"Actinium-225/Bismuth-213 supply and application barriers (Cancers, 2025)","url":"https://www.mdpi.com/2072-6694/17/18/3055"}],"tags":[],"related":["f-radioligand-therapy","f-isotope-supply","f-bone-targeted","lu-177","ac-225","ra-223"],"indications":["prostate-mcrpc","neuroendocrine","metastatic-ppgl"],"sections":[],"technologies":["targeted-alpha-therapy","actinium-225-supply","astatine-211-alpha-therapy","alpha-nanogenerators"],"targets":[],"drugs":["ac225-psma","fpi-2265","ryz101","alphamedix","radium-223"],"companies":["fusion-pharma","rayzebio","perspective-therapeutics","orano-med","actinium-pharmaceuticals","artbio","convergent-therapeutics"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":["alsympca","alphabreak","nct05219500"],"people":[],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":["Global 225Ac supply (~63 GBq/year) covers only about 100-200 patient treatments a year against an estimated demand of ~185 GBq/year and rising (IAEA TECDOC-2057, 2024).","No alpha-PSMA agent has randomised phase 3 evidence yet; current clinical use is investigational or salvage after lutetium-177.","The IAEA's Global Radium-226 Management Initiative is recovering legacy radium sources from roughly 80 countries as feedstock for 225Ac, a genuinely new supply route rather than incremental reactor capacity."],"order":3,"route":"/fronts/f-alpha-therapy/"}
{"id":"f-isotope-supply","kind":"section","name":"Isotope supply","aka":[],"tldr":"The radioactive ingredients in these medicines are made in a small number of ageing reactors and accelerators worldwide, and demand is now growing faster than that supply.","summary":"Every radiopharmaceutical begins as an isotope made in a reactor or accelerator, and the whole field sits on a genuinely fragile production base. Roughly 95% of the world's molybdenum-99 (the parent of technetium-99m, used in about 30 million SPECT scans a year, 80% of all nuclear medicine imaging) comes from a handful of research reactors in South Africa, the Netherlands, Belgium and Australia; because Mo-99's half-life is 66 hours it cannot be stockpiled, so a reactor outage cancels scans within days (OECD-NEA, 2025 review of medical radioisotope supply).\n\nLutetium-177 demand rose sharply after Pluvicto's approval, and the OECD-NEA and IAEA both project that non-carrier-added Lu-177 production capacity will not keep pace with clinical demand; a key bottleneck is enriched ytterbium-176 target material, historically sourced mainly from Russia. New capacity is being built to close the gap: Canada's Darlington reactor began isotope production runs (Mo-99, Lu-177, Y-90) from 2025; India's Dhruva reactor supplies domestic Lu-177 and imports the shortfall from Russia; SHINE Technologies (Chrysalis facility, Wisconsin) is targeting over 75% of US Mo-99 demand with a $263 million DOE conditional loan commitment, and is already producing Lu-177; and Eden Radioisotopes has filed a US NRC construction permit for a new Mo-99/Lu-177 facility aiming to supply up to 50% of global Mo-99 demand.\n\nActinium-225 has its own, much tighter, constraint (see the alpha-therapy front): global supply of roughly 63 GBq/year against rising clinical trial demand. Ideas circulating to fix the underlying fragility include a coordinated international reserve and shared production schedule across the world's medical isotope reactors, Western enrichment capacity for ytterbium-176 so Lu-177 has more than one supplier, and a global isotope supply observatory that forecasts shortages before they hit clinics.","asOf":"2026-09-22","links":[{"label":"OECD-NEA: Current trends in the supply and utilisation of medical radioisotopes (2025)","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"Eden Radioisotopes files NRC construction permit for Mo-99/Lu-177 facility (ANS, May 2026)","url":"https://www.ans.org/news/2026-05-08/article-8016/eden-targets-domestic-medical-radioisotope-production/"},{"label":"IAEA/OECD-NEA: Towards a robust supply chain for medical radioisotopes","url":"https://inis.iaea.org/records/06vmc-y0w54"}],"tags":[],"related":["f-alpha-therapy","f-radiochemistry","f-radioligand-therapy","tc-99m","mo-99","lu-177","ac-225","y-90"],"indications":[],"sections":[],"technologies":["therapy-isotope-supply-chain","research-reactor-isotope-production","cyclotron-isotope-production","actinium-225-supply","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["ansto","ire","nordion","northstar-medical-radioisotopes","shine-technologies","terrapower-isotopes","isotopia","curium"],"institutions":["iaea"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Mo-99's 66-hour half-life means it cannot be stockpiled; the physics of decay, not inventory management, sets the logistics of the whole Tc-99m supply chain.","Enriched ytterbium-176, the target material for non-carrier-added Lu-177, has historically depended heavily on Russian supply; Western enrichment capacity is only now being built out.","PALLAS/OECD-NEA modelling projects Lu-177 demand outpacing available capacity from around 2025 onward without new reactor investment."],"order":4,"route":"/fronts/f-isotope-supply/"}
{"id":"f-radiochemistry","kind":"section","name":"Radiochemistry & manufacturing","aka":[],"tldr":"Making one of these medicines means attaching a radioactive atom to a targeting molecule and getting it sterile and out the door within hours, before it decays away — a manufacturing problem unlike almost any other medicine.","summary":"Radiopharmaceutical chemistry starts by conjugating a chelator (most commonly DOTA or DOTAGA for metal radionuclides) onto a targeting ligand — a peptide, small molecule or antibody — via amine, thiol or click chemistry, then radiolabelling it with the chosen isotope, purifying it and formulating a sterile, injectable dose, all under current Good Manufacturing Practice. Antibody-based agents (e.g. 89Zr- or 177Lu-labelled antibodies) traditionally use random lysine conjugation, which gives a heterogeneous chelator-to-antibody ratio; site-specific conjugation methods are increasingly used to improve consistency and preserve binding affinity, though the benefit has to be demonstrated for each individual product (EJNMMI Radiopharm Chem, 2024).\n\nRegulatorily, radiopharmaceuticals are treated as their own category: the EMA's draft revised guideline on the quality of radiopharmaceuticals (consultation closed 30 April 2026) sets out that manufacturing dossiers must describe the process from the nuclear transformation step onward, and that radionuclidic and radiochemical impurities need their own control strategy distinct from ordinary small-molecule drug substances. In the UK, amended Clinical Trials Regulations (in force 28 April 2026) set out which manufacturing and QP-certification steps for radiopharmaceutical investigational medicinal products can be split between an MIA(IMP) licence holder and an MS-licensed radiolabelling site.\n\nThe unresolved manufacturing problem is scale-up: batch sizes are defined by total radioactivity rather than mass, decay clocks run throughout production and shipping, and sterility testing often cannot be completed before a short-lived product must be released and administered, which is why radiopharmaceutical GMP release strategies (parametric release, real-time release testing) are an active area rather than a solved one.","asOf":"2026-09-22","links":[{"label":"EMA draft guideline on the quality of radiopharmaceuticals, revision 2 (consultation closed 30 April 2026)","url":"https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-quality-radiopharmaceuticals-revision-2_en.pdf"},{"label":"Good practices for 89Zr radiopharmaceutical production and conjugation (EJNMMI Radiopharm Chem, 2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11088613/"},{"label":"MHRA: GMP and radiopharmaceutical investigational medicinal products guidance (updated 28 April 2026)","url":"https://www.gov.uk/guidance/clinical-trials-for-medicines-good-manufacturing-practice-and-radiopharmaceutical-investigational-medicinal-products"}],"tags":[],"related":["f-isotope-supply","f-regulation-reimbursement","zr-89","lu-177"],"indications":[],"sections":[],"technologies":["medical-cyclotrons-synthesis-modules","radiopharmaceutical-gmp-release","site-specific-conjugation","sterile-fill-finish","radionuclide-generators-kits","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":["trasis","comecer","eckert-ziegler","iba","jubilant-radiopharma","curium","nucleus-radiopharma","evergreen-theragnostics"],"institutions":["ema","mhra"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Sterility testing of short-lived radiopharmaceuticals often cannot be completed before the product must be released and injected, because the isotope decays before the assay returns — this is a structural, not a compliance, problem.","Site-specific conjugation improves consistency over random lysine labelling for antibody-based agents, but the clinical benefit has to be shown for each product individually; it is not yet a universal standard.","The EMA's revised radiopharmaceutical quality guideline (public consultation closed April 2026) has not yet been finalised as of this record's date."],"order":5,"route":"/fronts/f-radiochemistry/"}
{"id":"f-dosimetry","kind":"section","name":"Dosimetry","aka":[],"tldr":"Dosimetry works out exactly how much radiation dose a patient's tumour and healthy organs actually receive, so treatment can in principle be tailored to the person rather than given as one fixed dose to everyone.","summary":"Most approved radioligand therapy today is given as a fixed activity on a fixed schedule — 7.4 GBq of 177Lu-PSMA-617 every six weeks for up to six cycles, or 7.4 GBq of 177Lu-DOTATATE every eight weeks for four cycles — regardless of how much radiation dose that delivers to an individual patient's tumour, kidneys or bone marrow. Reported organ doses vary widely between patients: EANM dosimetry committee data for 90Y-DOTATOC give roughly 1.7-2.8 Gy/GBq to the kidneys, compared with about 0.6-0.9 Gy/GBq for 177Lu-DOTATATE, and comparable heterogeneity is reported for PSMA ligands.\n\nPersonalised, dosimetry-guided dosing has clear proof of principle outside radioligand therapy: in the DOSISPHERE-01 trial of yttrium-90 radioembolisation for hepatocellular carcinoma, a personalised multi-compartment dosimetry approach (target ≥205 Gy to the tumour) produced a median overall survival of 26.6 months versus 10.7 months with standard single-compartment dosing (HR 0.42, Garin et al., Lancet Gastroenterol Hepatol 2021). Bringing that logic to radioligand therapy is technically harder because it needs serial SPECT/CT or blood sampling after each cycle, and pure beta-emitters like 90Y have no gamma emission for direct imaging.\n\nThe field has not reached consensus on whether this is worth mandating. EANM's 2025 response to the EMA's concept paper on clinical evaluation of therapeutic radiopharmaceuticals states plainly that \"given the current lack of conclusive clinical evidence,\" it does not hold a definitive position on recommending extensive individual dosimetry, simplified approaches, or fixed-activity posology, and asks regulators not to mandate dose-planned prescribing until the evidence and harmonised methods exist. This is the single biggest open methodological question in the field: whether individualised dosimetry meaningfully improves outcomes enough to justify its cost and complexity in routine practice, versus in trials only.","asOf":"2026-09-22","links":[{"label":"EANM reply to EMA concept paper on clinical evaluation of therapeutic radiopharmaceuticals (Jan 2025)","url":"https://eanm.org/wp-content/uploads/2025/02/EANM-Reply-to-the-public-consultation-on-the-European-Medicines-Agency-Concept-paper-on-clinical-evaluation-of-therapeutic-radiopharmaceuticals-in-oncology.pdf"},{"label":"DOSISPHERE-01 trial (Garin et al., Lancet Gastroenterol Hepatol 2021)","url":"https://www.onclive.com/view/personalized-radioembolization-improves-os-vs-standard-dosing-in-advanced-hcc"},{"label":"EANM dosimetry committee recommendations for 177Lu-labelled SSTR- and PSMA-targeting ligands","url":"https://eanm.org/publications/guidelines/overview/dosimetry/"}],"tags":[],"related":["f-radioligand-therapy","f-radioembolisation","f-regulation-reimbursement","lu-177","y-90"],"indications":["neuroendocrine","hcc","prostate-mcrpc"],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","quantitative-imaging-biomarkers"],"targets":[],"drugs":[],"companies":[],"institutions":["eanm","snmmi"],"pathways":[],"terms":["dosimetry","gray-unit"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["EANM's own 2025 position is that it does not have enough conclusive clinical evidence to recommend mandatory individual dosimetry over fixed-activity dosing for radioligand therapy.","DOSISPHERE-01 is the clearest randomised proof that personalised dosimetry changes outcomes, but it is a radioembolisation trial, not a radioligand-therapy trial; the same case has not yet been made with equivalent rigour for 177Lu-PSMA or 177Lu-DOTATATE.","Pure beta-emitters without a useful gamma line (e.g. 90Y) cannot be imaged directly for dosimetry, which is a physical, not just logistical, constraint on personalising some regimens."],"order":6,"route":"/fronts/f-dosimetry/"}
{"id":"f-neuro-imaging","kind":"section","name":"Neuro-imaging","aka":[],"tldr":"Brain PET scans can now show the sticky protein clumps of Alzheimer's disease directly, and are also used to see how far a brain tumour has spread and whether radiotherapy scarring looks like tumour regrowth.","summary":"Amyloid and tau PET are the most consequential recent additions to neuro-imaging: the 2025 Appropriate Use Criteria from the Alzheimer's Association and SNMMI (updated from 2013, published simultaneously in Alzheimer's & Dementia and the Journal of Nuclear Medicine) rated 7 of 17 clinical scenarios as appropriate for amyloid PET and 5 of 17 for tau PET, chiefly assessment and prognosis of mild cognitive impairment, working up dementia of unclear cause, and determining eligibility for and monitoring response to anti-amyloid immunotherapies. Under the 2024 Alzheimer's Association diagnostic criteria, amyloid PET is a \"Core 1\" biomarker sufficient to establish the diagnosis, while tau PET is a \"Core 2\" biomarker used to stage disease once diagnosis is established.\n\nFDG PET keeps a distinct, complementary role in distinguishing Alzheimer's disease from other dementia subtypes by its regional pattern of hypometabolism, and is also used in neuro-oncology to help separate tumour recurrence from radiation necrosis after treatment for glioma or meningioma, a distinction that is often difficult on structural MRI alone. Somatostatin receptor PET (68Ga-DOTATATE) has become the imaging standard for meningioma, matching the joint EANM/EANO/RANO/SNMMI theranostics practice guideline that also covers SSTR-ligand radionuclide therapy for meningioma.\n\nWhat remains unsolved: expanded reimbursement for amyloid and tau PET has improved access in the US, but availability and payer coverage still vary widely internationally, and the AUC explicitly discourage use of these scans outside a proper dementia-specialist workup (for example, they are rated rarely appropriate for asymptomatic people who simply carry the APOE4 risk gene). Radiation necrosis after stereotactic radiotherapy remains genuinely difficult to distinguish from recurrent tumour even with modern PET tracers in a meaningful minority of cases.","asOf":"2026-09-22","links":[{"label":"Updated Appropriate Use Criteria for Amyloid and Tau PET (J Nucl Med / Alzheimer's & Dementia, 2025)","url":"https://jnm.snmjournals.org/content/early/2025/01/07/jnumed.124.268756"},{"label":"SNMMI news release: updated AUC for amyloid and tau PET (Jan 2025)","url":"https://snmmi.org/Web/Web/News/Articles/SNMMI-and-the-Alzheimer-s-Association-Release-Updated-Appropriate-Use-Criteria-for-Amyloid-and-Tau-P.Mobile.aspx"},{"label":"PET imaging in Alzheimer disease in the era of antiamyloid therapy (J Nucl Med Technol, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/41667280/"}],"tags":[],"related":["f-molecular-imaging","f-dosimetry","ga-68"],"indications":["glioblastoma","meningioma"],"sections":[],"technologies":["pet","pet-ct","pet-mri","sstr-pet","fdg-pet"],"targets":[],"drugs":[],"companies":["ge-healthcare","siemens-healthineers","canon-medical"],"institutions":["snmmi"],"pathways":[],"terms":["radiation-necrosis"],"trials":[],"people":["peter-bartenstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The 2025 SNMMI/Alzheimer's Association AUC explicitly discourage amyloid or tau PET in people with no cognitive impairment, even if they carry the APOE4 risk allele, and in place of genetic testing for suspected causal mutations.","Distinguishing radiation necrosis from tumour recurrence on PET after brain radiotherapy remains genuinely difficult in a meaningful minority of cases; no single tracer resolves it definitively.","Coverage and access for amyloid/tau PET have expanded in the US but remain uneven internationally."],"order":7,"route":"/fronts/f-neuro-imaging/"}
{"id":"f-cardiac-imaging","kind":"section","name":"Cardiac imaging","aka":[],"tldr":"A radioactive tracer injected into the bloodstream lights up on a scanner wherever the heart muscle is getting enough blood flow, so doctors can see blocked arteries without surgery.","summary":"Nuclear cardiology's long-standing tools are SPECT myocardial perfusion imaging with technetium-99m agents, and PET perfusion imaging with 82Rb, 13N-ammonia or 15O-water, the last two requiring an on-site cyclotron or generator that limits which centres can offer PET perfusion at all. The field's biggest recent development is the FDA approval, on 27 September 2024, of flurpiridaz F-18 (Flyrcado, GE HealthCare/Lantheus) for PET myocardial perfusion imaging under rest or stress (pharmacologic or exercise) in adults with known or suspected coronary artery disease — the first new perfusion radiopharmaceutical approved by the FDA in nearly 30 years, based on the phase 3 AURORA trial and prior studies.\n\nFlurpiridaz's practical advantage is that, unlike 82Rb or 13N-ammonia, its 110-minute fluorine-18 half-life allows it to be manufactured centrally at a regional cyclotron and shipped as a unit dose to hospitals that have no cyclotron or generator of their own, which nuclear cardiology commentary expects to expand access to PET perfusion imaging considerably. It also allows quantification of absolute myocardial blood flow and myocardial flow reserve, similar to 13N-ammonia and 82Rb.\n\nWhat is still unresolved: the FDA approval of flurpiridaz explicitly does not change existing PET myocardial perfusion imaging appropriate-use criteria, so its clinical positioning relative to SPECT and to the older PET perfusion tracers is still being worked out in practice, and real-world access will depend on how widely regional cyclotron-supplied unit doses actually reach community hospitals rather than only academic centres with existing PET infrastructure.","asOf":"2026-09-22","links":[{"label":"FDA: approval of Flyrcado (flurpiridaz F 18) for myocardial ischemia/infarction evaluation, 27 Sep 2024","url":"https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-imaging-drug-evaluation-myocardial-ischemia-and-infarction"},{"label":"FLYRCADO prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3bb6caf8-ac98-46c7-a9f0-961e66032705&type=display"},{"label":"FDA approval of 18F-flurpiridaz for PET: stepping into a new era of MPI (J Nucl Med, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12175995/"},{"label":"ASNC: F-18 flurpiridaz FDA approval announcement","url":"https://www.asnc.org/news/f18-flurpiridaz-fda-approval-nuclear-cardiologys-new-radiotracer-for-cardiac-pet-imaging/"}],"tags":[],"related":["f-molecular-imaging","f-18","tc-99m","n-13","o-15","rb-82"],"indications":[],"sections":[],"technologies":["pet","pet-ct","spect","spect-ct"],"targets":[],"drugs":[],"companies":["ge-healthcare","lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["FDA approval of flurpiridaz F-18 (Flyrcado, 27 September 2024) explicitly does not change existing PET myocardial perfusion appropriate-use criteria; its place in the diagnostic pathway relative to SPECT and older PET tracers is still being worked out.","Flurpiridaz's 110-minute half-life allows central cyclotron manufacture and unit-dose shipping, unlike 82Rb (generator-based) or 13N-ammonia (needs an on-site cyclotron); whether this actually expands access to community hospitals in practice is not yet demonstrated at scale."],"order":8,"route":"/fronts/f-cardiac-imaging/"}
{"id":"f-infection-imaging","kind":"section","name":"Infection & inflammation imaging","aka":[],"tldr":"The same FDG tracer used to find cancer also lights up sites of infection and inflammation, which helps doctors find hidden abscesses, infected joint replacements or heart-valve infections that scans and blood tests alone can miss.","summary":"FDG PET/CT is now the best-evidenged nuclear medicine tool for infection and inflammation outside oncology, formalised in the EANM/SNMMI guideline/procedure standard for [18F]FDG hybrid PET use in infection and inflammation in adults, version 2.0 (Abikhzer et al., Eur J Nucl Med Mol Imaging 2025), which defines protocols and interpretation criteria across 19 indications, from bacteraemia and suspected spondylodiscitis to endocarditis, vascular graft infection and periprosthetic joint infection. For periprosthetic joint infection specifically, a pooled analysis cited in the guideline reports FDG PET sensitivity of about 85% and specificity of about 86% across 23 studies (1,437 patients), and the guideline states that the absence of periprosthetic uptake reliably excludes infection in both hip and knee prostheses, while a positive scan needs careful interpretation because aseptic loosening, recent surgery and metal-related artefact can all cause false-positive uptake.\n\nWhite blood cell scintigraphy remains the preferred confirmatory test when FDG PET/CT is inconclusive, particularly for prosthetic joint and vascular graft infection, because it retains higher specificity than FDG in that specific setting even though FDG PET/CT is now the first-line hybrid imaging test for most of the 19 defined indications. A separate EANM/EBJIS/ESR consensus document (with ESCMID endorsement) sets out the broader multimodality diagnostic pathway for prosthetic joint infection, in which nuclear imaging is one component alongside clinical, microbiological and structural imaging criteria.\n\nWhat the 2025 guideline explicitly flags as unresolved: it found insufficient evidence to support FDG PET/CT as a standard indication for COVID-19 (including long COVID), interstitial lung disease, or inflammatory arthropathies and myopathies, while noting evidence may emerge in future. SUV and target-to-background ratios, validated as semi-quantitative measures in oncology, have not been generally validated for distinguishing infection from sterile inflammation or malignancy and the guideline says they should be used with caution.","asOf":"2026-09-22","links":[{"label":"EANM/SNMMI guideline/procedure standard for FDG hybrid PET in infection and inflammation v2.0 (Eur J Nucl Med Mol Imaging, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11732780/"},{"label":"JNM summary: EANM/SNMMI FDG hybrid PET infection/inflammation guideline v2.0","url":"https://jnm.snmjournals.org/content/early/2025/02/06/jnumed.125.269538"},{"label":"EANM: Inflammation/Infection guideline overview page","url":"https://eanm.org/publications/guidelines/overview/inflammation-infection/"}],"tags":[],"related":["f-molecular-imaging","f-18"],"indications":[],"sections":[],"technologies":["fdg-pet","spect","gamma-probes-dose-calibrators"],"targets":[],"drugs":["fludeoxyglucose-f18","technetium-sulfur-colloid","tilmanocept-tc99m"],"companies":[],"institutions":["eanm","snmmi"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The 2025 EANM/SNMMI guideline found insufficient evidence to add COVID-19 (including long COVID), interstitial lung disease, or inflammatory arthropathies/myopathies as supported indications, though it leaves the door open as evidence accumulates.","SUV and target-to-background ratios are not generally validated for distinguishing infection from sterile inflammation or malignancy, unlike their established role in oncology; the guideline recommends caution.","White blood cell scintigraphy keeps a role as the confirmatory test when FDG PET/CT is inconclusive, especially around prosthetic joints, because false-positive FDG uptake from aseptic loosening or recent surgery is a recognised limitation."],"order":9,"route":"/fronts/f-infection-imaging/"}
{"id":"f-bone-targeted","kind":"section","name":"Bone-targeted radiopharmaceuticals","aka":[],"tldr":"Some radioactive drugs are built to home in on damaged bone rather than the tumour itself, easing bone pain from cancer that has spread to the skeleton and, in one case, helping patients live longer.","summary":"Bone-targeted radiopharmaceuticals exploit the fact that metastatic bone lesions have abnormally high bone turnover. Radium-223 dichloride behaves as a calcium mimetic, concentrating in newly formed bone matrix next to osteoblastic metastases, where its alpha-particle emissions cause localised DNA damage. It is the only bone-targeted radiopharmaceutical shown to extend overall survival: the phase 3 ALSYMPCA trial (921 patients with symptomatic, bone-predominant, castration-resistant prostate cancer without known visceral metastases) showed improved overall survival and delayed skeletal-related events against placebo plus best supportive care. Older agents — samarium-153 lexidronam and phosphorus-32 — and strontium-89 (not in wide current use) give palliative pain relief from bone metastases but have not shown a survival benefit.\n\nRadium-223's use has narrowed rather than widened since approval. The ERA-223 trial found that combining it with abiraterone and prednisone/prednisolone raised fracture incidence sharply (28.6% vs 11.4%) with no offsetting clinical benefit, so that combination is now contraindicated, and current guidance restricts radium-223 to bone-predominant mCRPC without visceral metastases, typically after at least two prior systemic therapies or in patients unfit for them. A phase 2 trial reported in 2026 (RADICAL, Alliance A031801, JCO) tested adding radium-223 to cabozantinib in bone-metastatic renal cell carcinoma and found no improvement in symptomatic skeletal event-free survival, progression-free survival or overall survival, and closed early for futility — a reminder that radium-223's prostate-cancer benefit does not automatically generalise to other bone-metastatic cancers.\n\nWhat remains unsolved: assessing whether radium-223 is actually working is harder than for most cancer drugs, because it does not shrink lesions in the way conventional RECIST-based imaging expects and its target is bone remodelling rather than the tumour directly; a 2026 review in Seminars in Nuclear Medicine surveys the resulting patchwork of serum biomarkers, liquid biopsy markers and imaging approaches (18F-fluoride PET/CT, whole-body diffusion MRI, PSMA PET/CT) used to judge response, without a single validated standard emerging.","asOf":"2026-09-22","links":[{"label":"ALSYMPCA trial (Parker et al., NEJM 2013)","url":"https://www.nejm.org/doi/10.1056/NEJMoa1213755"},{"label":"RADICAL trial (Alliance A031801): radium-223 + cabozantinib in mRCC (JCO, 27 Jul 2026)","url":"https://oncodaily.com/genitourinary-oncology/radical-2"},{"label":"Assessing therapeutic response to radium-223 (Semin Nucl Med, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/41412927/"},{"label":"Bone-targeting radionuclides in mCRPC: review of radium-223 combinations (Diagnostics, 2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11544963/"}],"tags":[],"related":["f-alpha-therapy","f-radioligand-therapy","f-18","ra-223","sm-153","sr-89","p-32"],"indications":["prostate-mcrpc","rcc","bone-metastases"],"sections":[],"technologies":["spect"],"targets":[],"drugs":["radium-223","samarium-153-lexidronam","phosphorus-32"],"companies":["bayer"],"institutions":[],"pathways":[],"terms":["bone-metastases"],"trials":["alsympca"],"people":[],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":["Radium-223 plus abiraterone/prednisone is contraindicated after ERA-223 found a sharply higher fracture rate (28.6% vs 11.4%) with no clinical benefit.","The 2026 RADICAL trial found no benefit from adding radium-223 to cabozantinib in bone-metastatic renal cell carcinoma, closing early for futility — radium-223's prostate-cancer survival benefit has not generalised to other tumour types tested so far.","There is no single validated method for assessing radium-223 response; conventional RECIST imaging is a poor fit because the drug targets bone remodelling rather than shrinking the tumour directly."],"order":10,"route":"/fronts/f-bone-targeted/"}
{"id":"f-radioembolisation","kind":"section","name":"Radioembolisation","aka":[],"tldr":"Radioembolisation delivers tiny radioactive beads directly into the blood vessels feeding a liver tumour through a catheter, so the radiation stays concentrated in the liver instead of spreading through the whole body.","summary":"Transarterial radioembolisation (TARE), also called selective internal radiation therapy (SIRT), delivers yttrium-90-loaded microspheres (glass, e.g. TheraSphere, or resin, e.g. SIR-Spheres) through a hepatic artery catheter to treat unresectable hepatocellular carcinoma, and is also used for liver-dominant metastases from colorectal cancer and neuroendocrine tumours. The pivotal SARAH and SIRveNIB trials tested Y-90 TARE against sorafenib in advanced HCC and found radioembolisation was not superior to systemic therapy on survival, which tempered early enthusiasm for TARE as a stand-alone replacement for systemic treatment in advanced disease.\n\nThe practice-changing development since has been personalised dosimetry. The randomised phase 2 DOSISPHERE-01 trial compared a standard single-compartment dosing approach (target 120±20 Gy to the perfused liver lobe) against a personalised multi-compartment approach targeting at least 205 Gy to the tumour in locally advanced HCC, and found median overall survival of 26.6 months with personalised dosing versus 10.7 months with standard dosing (HR 0.42, 95% CI 0.22-0.83, p=0.0096), with objective response 71.4% versus 35.7% and 36% of personalised-arm patients downstaged to surgery versus 4% in the standard arm (Garin et al., Lancet Gastroenterol Hepatol 2021). This has shifted practice guidance toward partition-model dosimetry using pre-treatment MAA SPECT rather than fixed body-surface-area dosing.\n\nWhat is still unsettled: TARE's role relative to newer systemic options (immunotherapy combinations, TACE) in intermediate-stage disease is being re-tested in ongoing trials combining radioembolisation with checkpoint inhibitors (e.g. durvalumab and bevacizumab), and while personalised dosimetry clearly improves outcomes in the DOSISPHERE-01 population, routine adoption of partition-model dosimetry across centres worldwide is uneven, similar to the dosimetry debate in radioligand therapy.","asOf":"2026-09-22","links":[{"label":"DOSISPHERE-01 trial (Garin et al., Lancet Gastroenterol Hepatol 2021)","url":"https://www.onclive.com/view/personalized-radioembolization-improves-os-vs-standard-dosing-in-advanced-hcc"},{"label":"DOSISPHERE-01 data sheet (Boston Scientific)","url":"https://www.bostonscientific.com/content/dam/bostonscientific/pi/portfolio-group/cancer-therapies/therasphere/resource-center/clinical-data/DOSISPHERE-01_Data_Sheet.pdf"},{"label":"Advances and emerging techniques in Y-90 radioembolisation for HCC (Cancers, 2025)","url":"https://www.mdpi.com/2072-6694/17/9/1494"}],"tags":[],"related":["f-dosimetry","f-bone-targeted","y-90"],"indications":["hcc","hcc-intermediate"],"sections":[],"technologies":["radioembolisation-tare"],"targets":[],"drugs":[],"companies":["sirtex","boston-scientific"],"institutions":[],"pathways":[],"terms":["tare"],"trials":["sarah-sirvenib","nct06040099"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["SARAH and SIRveNIB both found Y-90 TARE was not superior to sorafenib on survival in advanced HCC, so TARE has not replaced systemic therapy in that setting.","DOSISPHERE-01 is the clearest randomised evidence that personalised, partition-model dosimetry meaningfully changes outcomes in radioembolisation (median OS 26.6 vs 10.7 months), but routine uptake of this dosimetry approach still varies by centre.","Trials combining TARE with checkpoint inhibitors and anti-angiogenics (e.g. durvalumab/bevacizumab, NCT06040099) are testing whether locoregional and systemic immunotherapy combine safely and effectively; results are pending."],"order":11,"route":"/fronts/f-radioembolisation/"}
{"id":"f-regulation-reimbursement","kind":"section","name":"Regulation & reimbursement","aka":[],"tldr":"Getting one of these radioactive medicines approved and then actually paid for is its own specialised process, separate from ordinary drugs, and the rules for who pays what changed again for 2026 in the US.","summary":"Radiopharmaceuticals are regulated as a distinct drug category. In the US, the FDA reviews and approves them under the same statutory framework as other drugs but with radiopharmaceutical-specific guidance on chemistry, manufacturing and controls; in the EU the EMA's guideline on the quality of radiopharmaceuticals is being revised (draft revision 2, public consultation closed 30 April 2026) to update how manufacturing dossiers describe the process from radionuclide production onward and how radionuclidic/radiochemical impurities are controlled. The UK's MHRA updated its clinical-trials GMP guidance for radiopharmaceutical investigational medicinal products, effective 28 April 2026, clarifying which manufacturing and QP-certification steps can be split between licensed facilities.\n\nPayment is a separate and increasingly consequential fight, especially in the US Medicare system. Under the CY2026 Hospital Outpatient Prospective Payment System final rule, CMS raised the per-day cost threshold above which diagnostic radiopharmaceuticals are paid separately (using hospital-claims-derived mean unit cost) from $630 to $655, continuing a policy that packages lower-cost diagnostic tracers into the payment for the imaging procedure itself rather than paying for them separately — a policy nuclear medicine societies have long argued undervalues newer, higher-cost diagnostic agents. CMS also created a new $10-per-dose add-on payment, effective 1 January 2026, for technetium-99m doses derived from domestically produced molybdenum-99 (HCPCS code C9176, requiring at least 50% of the Mo-99 to have been both irradiated and processed in the US), replacing an earlier add-on that had rewarded non-highly-enriched-uranium production regardless of country of origin. Separately payable therapeutic radiopharmaceuticals without pass-through status continue to be paid at ASP+6%, falling back to WAC+3% or 95% of AWP when ASP or WAC data are unavailable.\n\nWhat remains unresolved: ASP (average sales price) reporting for diagnostic radiopharmaceuticals is still voluntary under CMS rules for 2026, which limits how accurately the mean-unit-cost proxy reflects true market prices, and CMS says it \"intends to explore\" updated ASP-reporting guidance without having committed to a firm change. Medicare's coverage-with-evidence-development pathway continues to gate access to some newer radiopharmaceuticals pending real-world outcomes data, and reimbursement policy differs enough between the US, the EU (EMA/national payers) and other regulators (Japan's PMDA, the UK's MHRA) that global access to a newly approved agent can lag its first approval by years.","asOf":"2026-09-22","links":[{"label":"CMS: Hospital Outpatient Prospective Payment System, January 2026 update (MM14361)","url":"https://www.cms.gov/files/document/mm14361-hospital-outpatient-prospective-payment-system-january-2026-update.pdf"},{"label":"Sidley: Medicare payment policy final rule for outpatient setting addresses radiopharmaceuticals (Dec 2025)","url":"https://www.sidley.com/en/insights/newsupdates/2025/12/medicare-payment-policy-final-rule-for-outpatient-setting-addresses-radiopharmaceuticals"},{"label":"EMA: draft guideline on the quality of radiopharmaceuticals, revision 2","url":"https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-quality-radiopharmaceuticals-revision-2_en.pdf"},{"label":"MHRA: clinical trials GMP and radiopharmaceutical IMPs guidance (updated 28 April 2026)","url":"https://www.gov.uk/guidance/clinical-trials-for-medicines-good-manufacturing-practice-and-radiopharmaceutical-investigational-medicinal-products"}],"tags":[],"related":["f-radiochemistry","f-dosimetry","f-isotope-supply","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ema","mhra","pmda","snmmi","eanm"],"pathways":[],"terms":["medicare-ced"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["ASP reporting for diagnostic radiopharmaceuticals remains voluntary under the CY2026 OPPS rule; CMS says it intends to explore updated guidance but has not mandated reporting.","The $10 domestic-Mo-99 add-on payment (HCPCS C9176, effective 1 Jan 2026) replaced an earlier add-on tied to non-HEU production rather than country of origin — a policy shift toward reshoring rather than just proliferation-resistant production methods.","Regulatory and reimbursement timelines are not synchronised across the US, EU, UK and Japan, so global patient access to a newly approved radiopharmaceutical can lag its first approval by a substantial margin."],"order":12,"route":"/fronts/f-regulation-reimbursement/"}
{"id":"idea-tb161-instead-of-lu177","kind":"idea","name":"Terbium-161 instead of lutetium-177 in the same ligands","aka":[],"tldr":"Terbium-161 is a close chemical cousin of lutetium-177 that, as well as giving off the same kind of radiation, also releases a shower of extremely short-range electrons. In theory that extra radiation could finish off single cancer cells and tiny clusters that a lutetium-177 treatment might miss, using the same targeting molecules already in use.","summary":"Terbium-161 decays with a half-life of about 6.95 days and emits beta particles similar in energy to lutetium-177's, plus roughly ten times more conversion and Auger electrons per decay. These electrons travel only nanometres to micrometres, so preclinical dosimetry modelling (Champion et al.; Müller et al.) predicts 2-3-fold higher absorbed dose to single cells and micrometastases than lutetium-177 at the same injected activity, while producing only modestly higher organ doses to kidney and salivary gland. Because terbium-161 is chemically a lanthanide like lutetium-177, the same DOTA-based chelators and labelling protocols can be reused for PSMA and somatostatin-receptor ligands.\n\nClinical translation is under way but not yet comparative. The first-in-human VIOLET trial at Peter MacCallum Cancer Centre (NCT05521412, 30 patients with metastatic castration-resistant prostate cancer) established that 161Tb-PSMA-I&T is feasible and safe up to 7.4 GBq, with organ doses similar to historical 177Lu-PSMA-617 data, and the study has since opened a 9.5 GBq expansion cohort. A German programme (REALITY, NCT04833517) is running an intra-individual head-to-head dosimetry comparison of 161Tb-PSMA-617 against 177Lu-PSMA-617 in the same patients. Neither trial has yet reported a comparative efficacy result, and global terbium-161 supply remains a research-scale bottleneck: the reactor-based no-carrier-added production route needed to avoid stable terbium contamination is far less mature than lutetium-177 supply chains.\n\nThe open question is whether the extra subcellular dose actually translates into better tumour control at a clinically tolerable normal-organ dose, rather than just a favourable dosimetry ratio in phantoms and mice.","asOf":"2026-09-22","links":[{"label":"Peter Mac / UCSF-UCLA PSMA Conference 2025: Michael Hofman on terbium-161 (VIOLET)","url":"https://www.urotoday.com/video-lectures/2025-ucsf-ucla-psma-conference/video/4752-beyond-lutetium-psma-exploring-terbium-161-for-treatment-resistant-prostate-cancer-presentation-michael-hofman.html"},{"label":"Terbium-161 in nuclear medicine: preclinical and clinical status (PubMed, 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/39978166/"},{"label":"Opportunities and potential challenges of using terbium-161 for targeted radionuclide therapy in clinics (EJNMMI, 2023)","url":"https://link.springer.com/article/10.1007/s00259-023-06316-y"},{"label":"From lutetium to terbium: a new era in PSMA-targeted radioligand therapy (PMC, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12629902/"}],"tags":["prostate","isotope alternative","auger electrons"],"related":["lu177-radioligand-therapy","prrt","radioligand-dosimetry","psma-pet","lu-177","tb-161"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Substituting terbium-161 for lutetium-177 in the same PSMA or somatostatin-receptor ligand will produce a higher objective response rate at an equivalent kidney and salivary-gland radiation dose, because terbium-161's additional Auger and conversion electrons deposit extra lethal energy in micrometastases that lutetium-177's longer-range beta particles largely miss.","rationale":"Preclinical dosimetry work (Müller et al., Grünberg et al., Champion et al.) consistently found terbium-161 delivers several-fold higher absorbed dose than lutetium-177 to single cells and small tumour clusters, and dual-isotope SPECT imaging confirmed the two radiolanthanides are pharmacokinetically interchangeable when attached to the same peptide. The first-in-human VIOLET trial (30 patients) showed 161Tb-PSMA-I&T is safe with organ doses comparable to 177Lu-PSMA-617, but was single-arm and not powered to detect an efficacy difference. No completed trial has yet reported a head-to-head efficacy comparison.","test":"A randomised phase 2 trial in metastatic castration-resistant prostate cancer comparing 161Tb-PSMA-I&T against 177Lu-PSMA-617 at kidney-dose-matched activities, powered on PSA50 response rate or PSMA-PET-defined progression-free survival, roughly 150-200 patients; the ongoing REALITY intra-individual dosimetry comparison (NCT04833517) is a smaller precursor step.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6,"route":"/ideas/idea-tb161-instead-of-lu177/"}
{"id":"idea-pretargeted-alpha-therapy","kind":"idea","name":"Pretargeted alpha radioimmunotherapy","aka":[],"tldr":"Instead of injecting a radioactive antibody that circulates in the blood for days, doctors first give a plain antibody that finds the tumour, wait for it to clear, then inject a small, fast-moving radioactive alpha payload that only attaches where the antibody is already waiting. This two-step trick could let radioactive antibodies treat solid tumours without poisoning the bone marrow.","summary":"Directly labelled antibodies carrying alpha emitters are attractive because alpha particles are extremely damaging over a very short range, but full-length antibodies circulate for days, so a directly labelled alpha antibody keeps irradiating blood and marrow long after most of it has left the tumour. Pretargeting separates the two steps: a bispecific antibody (one arm binds the tumour antigen, the other binds a small hapten) is given first and allowed to clear from circulation over hours to days, then a small radiolabelled hapten is injected and rapidly binds the antibody already sitting on the tumour, or clears from the body within hours if unbound.\n\nThe approach has a long clinical history with beta and gamma emitters going back over thirty years, including phase I/II trials of iodine-131 and lutetium-177 pretargeting in medullary thyroid cancer, small-cell lung cancer and CEA-positive colorectal cancer, but it has never reached market approval; a 2017 review notes that pretargeted lutetium-177/CEA trials in colorectal cancer were disappointing because tumour retention was too fast relative to lutetium-177's multi-day half-life. That mismatch is exactly why alpha emitters, most of which have half-lives of minutes to hours (bismuth-213, astatine-211), are now seen as a better fit for pretargeting's fast hapten kinetics. Preclinical proof of concept for alpha-pretargeting exists: a 2025 study from Memorial Sloan Kettering used a three-step regimen (anti-HER2/anti-DOTA bispecific antibody, a clearing agent, then actinium-225-labelled DOTA) to achieve complete responses in 20/20 HER2-positive breast cancer xenografts with tumour-to-kidney dose ratios of roughly 60:1 and no chronic nephrotoxicity at curative doses.\n\nNo alpha-emitter pretargeting regimen has yet been tested in patients; all current human experience with actinium-225 or bismuth-213 antibody therapy uses direct labelling (for example anti-CD33 225Ac antibodies in acute myeloid leukaemia).","asOf":"2026-09-22","links":[{"label":"225Ac alpha-pretargeted radioimmunotherapy of HER2-expressing breast cancer (J Nucl Med, 2025)","url":"https://jnm.snmjournals.org/content/early/2025/06/05/jnumed.125.269601"},{"label":"Pretargeting: A Path Forward for Radioimmunotherapy (PMC review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12079710/"},{"label":"Pretargeting for imaging and therapy in oncological nuclear medicine (PMC, 2017)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5824696/"}],"tags":["alpha therapy","antibody","pretargeting"],"related":["targeted-alpha-therapy","radioimmunotherapy","her2","ceacam5","lu-177","ac-225","i-131","bi-213","at-211"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A three-step pretargeting regimen (bispecific antibody, clearing agent, then an alpha-emitting hapten) will achieve a substantially higher tumour-to-normal-tissue radiation dose ratio than directly labelled alpha-emitting antibodies, enabling curative-intent alpha radioimmunotherapy of solid tumours without dose-limiting marrow or kidney toxicity.","rationale":"Mechanistically, pretargeting decouples the antibody's slow blood clearance from the radioactive payload's fast clearance, which matters most for alpha emitters whose half-lives (minutes to hours) are far shorter than an antibody's circulation time. Preclinical 225Ac-pretargeted radioimmunotherapy against HER2-positive breast cancer achieved 100% complete response and roughly 60:1 tumour:kidney dose ratios in two xenograft models without chronic nephrotoxicity at curative doses (Cheal, Santich et al., J Nucl Med 2025). Decades of clinical pretargeting experience exist with beta and gamma emitters (iodine-131, lutetium-177), establishing the two-step logistics and bispecific-antibody dosing are feasible in patients, but those beta-emitter trials had disappointing tumour retention. No alpha-emitter pretargeting regimen has been tested clinically.","test":"A first-in-human phase 1 dose-escalation trial of a pretargeted alpha regimen (bispecific antibody plus clearing agent, then an actinium-225- or bismuth-213-labelled hapten) in patients with a refractory HER2-positive or CEA-positive solid tumour, roughly 20-30 patients, with safety/maximum tolerated dose as the primary endpoint and surrogate imaging-based tumour dosimetry as a key secondary endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":10,"route":"/ideas/idea-pretargeted-alpha-therapy/"}
{"id":"idea-dosimetry-guided-dosing-standard","kind":"idea","name":"Kidney-dosimetry-guided dosing as the default for PSMA radioligand therapy","aka":[],"tldr":"Right now, most patients get the same number of treatment cycles at the same radioactive dose regardless of their own biology. Measuring how much radiation actually reaches each patient's kidneys after the first dose could let doctors safely give some patients more cycles and stop earlier in others, rather than using one fixed schedule for everyone.","summary":"The label dosing for lutetium-177 vipivotide tetraxetan (Pluvicto) is a fixed 7.4 GBq every six weeks for up to six cycles, as tested in the VISION trial, regardless of how much radiation an individual patient's kidneys, salivary glands or tumours actually receive. Dosimetry studies show this fixed approach leaves dose headroom in many patients: a single-institution series at the University of Wisconsin found that among 19 patients with post-cycle-one voxel-level SPECT/CT dosimetry, kidney and salivary gland absorbed doses tracked the VISION phase 3 benchmarks, and 15 of 19 patients could have safely received a seventh cycle and 18 of 19 an additional cycle based on a 24 Gy kidney and 20 Gy salivary gland threshold, while a smaller number needed early discontinuation or dose delay. In neuroendocrine tumour PRRT, the LUMEN and LUTADOSE studies found that tumour-absorbed dose measured after the first cycle predicts progression-free survival, reinforcing that a fixed four- or six-cycle schedule is a population average rather than a patient-specific optimum.\n\nSeveral trials are now testing personalised dosing directly rather than relying on retrospective series. FLEX-MRT (NCT06216249, UCLA, randomised phase 2, about 90 patients) compares a flexible, SPECT/CT-response-guided schedule of up to 12 cycles with treatment holidays against the standard fixed six-cycle regimen, with 2-year survival as the primary endpoint. PRODIGY-2 (NCT06943495, CHU de Québec) is testing whether renal-dosimetry-guided activity escalation is feasible and safe compared with the fixed-activity regimen. In neuroendocrine tumours, DOBATOC (NCT04917484) is a randomised phase 2 testing kidney-dose-governed individualised dosing (targeting a 24 Gy cumulative kidney dose) against fixed dosing, with progression-free survival as the primary outcome.\n\nThis proposal is deliberately broader than the existing dosimetry-personalised-PRRT idea already in this graph, which is specific to neuroendocrine tumours: the claim here is that dosimetry-guided dosing should become the default approach across radioligand therapies generally, including PSMA-targeted treatment, not just PRRT.","asOf":"2026-09-22","links":[{"label":"FLEX-MRT: Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 (ClinicalTrials.gov, NCT06216249)","url":"https://clinicaltrials.gov/study/NCT06216249"},{"label":"PRODIGY-2: Personalized vs. Fixed-Activity 177Lu-PSMA-617 (ClinicalTrials.gov, NCT06943495)","url":"https://clinicaltrials.gov/study/NCT06943495"},{"label":"Personalized Dosimetry Guides 177Lu-PSMA-617 Therapy (conference coverage, University of Wisconsin series)","url":"https://www.hmpgloballearningnetwork.com/site/rpei/conference-coverage/personalized-dosimetry-guides-177lu-psma-617-therapy-prostate-cancer"},{"label":"Radioligand therapy and tumor dosimetry: where are we and where are we going? (2026 review)","url":"https://link.springer.com/article/10.1007/s40336-026-00769-5"},{"label":"VISION: 177Lu-PSMA-617 (ClinicalTrials.gov, NCT03511664)","url":"https://clinicaltrials.gov/study/NCT03511664"}],"tags":["dosimetry","personalised dosing","prostate"],"related":["idea-net-dosimetry-prrt","radioligand-dosimetry","pluvicto","vision","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Replacing lutetium-177-PSMA-617's fixed six-cycle, fixed-activity regimen with a kidney-dosimetry-guided number of cycles and activity will let more patients safely receive additional beneficial cycles, and will identify others who should stop earlier, without exceeding organ-radiation-dose limits.","rationale":"A retrospective series of 19 patients found organ doses consistent with VISION trial benchmarks and identified that the great majority could have safely received extra cycles based on kidney and salivary gland dose thresholds. In neuroendocrine PRRT, the LUMEN and LUTADOSE studies independently found that cycle-one tumour-absorbed dose predicts progression-free survival, supporting the general principle that a fixed schedule under- or over-treats many patients. Multiple randomised trials (FLEX-MRT, PRODIGY-2, DOBATOC) are now directly testing personalised, dosimetry-guided dosing against fixed dosing; none has yet reported a mature result.","test":"FLEX-MRT (NCT06216249), an already-enrolling randomised phase 2 trial (approximately 90 patients) comparing a SPECT/CT-response-guided flexible dosing schedule of up to 12 cycles, including treatment holidays, against the standard fixed six-cycle regimen of 177Lu-PSMA-617, with 2-year survival as the primary endpoint; DOBATOC (NCT04917484) provides the analogous randomised test in neuroendocrine PRRT.","maturity":"being-tested-at-scale","actor":"research","cost":"medium","horizonYears":5,"route":"/ideas/idea-dosimetry-guided-dosing-standard/"}
{"id":"idea-rlt-plus-parp-inhibitor","kind":"idea","name":"Adding a PARP inhibitor to PSMA radioligand therapy","aka":[],"tldr":"A drug that blocks a cell's DNA-repair enzyme (PARP) is being added to PSMA-targeted radioactive treatment, on the theory that if a cell can't repair the small cuts radiation makes to its DNA, those cuts become fatal breaks that kill the cancer cell.","summary":"Lutetium-177-PSMA-617 kills cells mainly by causing single-strand breaks in DNA, which the cell can often repair using PARP-dependent base excision repair. PARP inhibitors such as olaparib block this repair pathway, and preclinical work has shown this can convert what would have been a survivable single-strand break into a lethal double-strand break, radiosensitising tumour cells.\n\nThe combination has been tested clinically in the LuPARP phase 1 trial (NCT03874884, Peter MacCallum Cancer Centre), which enrolled patients with metastatic castration-resistant prostate cancer who had progressed on an androgen receptor pathway inhibitor. Across ten dose-escalation cohorts of olaparib schedules combined with a fixed 7.4 GBq dose of 177Lu-PSMA-617 every six weeks for up to six cycles, no dose-limiting toxicities were reported; common adverse events were low-grade xerostomia, nausea and fatigue, with transient grade 1-3 cytopenias. Reported activity was promising: a PSA50 response rate of 62% and PSA90 of 48% were seen in an interim 29-patient analysis, and at the recommended phase 2 dose (an intermittent olaparib schedule starting four days before each lutetium cycle), the median radiographic progression-free survival was 12.8 months with a PSA90 response rate of 55%.\n\nA second, alpha-emitter version of this combination is now in trial: FPI-2265 (225Ac-PSMA-I&T) plus olaparib (NCT06909825) is testing whether the same DNA-repair rationale extends to alpha-particle radioligand therapy. Neither the beta nor the alpha combination has yet been tested in a randomised trial against radioligand therapy alone, so the magnitude of any added benefit over 177Lu-PSMA-617 or 225Ac-PSMA-I&T monotherapy is not yet established.","asOf":"2026-09-22","links":[{"label":"LuPARP: Phase 1 trial of 177Lu-PSMA-617 and olaparib in mCRPC (JCO, 2023)","url":"https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5005"},{"label":"177Lu-PSMA-617 Therapy and Olaparib in Patients With mCRPC (LuPARP) (ClinicalTrials.gov, NCT03874884)","url":"https://clinicaltrials.gov/study/NCT03874884"},{"label":"Recent Advances in Radioligand Therapy: LuPARP recommended phase 2 dose results","url":"https://nuclide-hema.healthbooktimes.org/article/154290-recent-advances-in-radioligand-therapy"},{"label":"FPI-2265 and Olaparib for Patients With mCRPC (ClinicalTrials.gov, NCT06909825)","url":"https://clinicaltrials.gov/study/NCT06909825"}],"tags":["combination therapy","PARP","prostate"],"related":["radionuclide-parp-combination","pluvicto","olaparib","fpi-2265","sandhu-shahneen","prostate-mcrpc","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding the PARP inhibitor olaparib to lutetium-177-PSMA-617 will increase the objective response rate in metastatic castration-resistant prostate cancer compared with radioligand therapy alone, by converting radiation-induced DNA single-strand breaks into lethal double-strand breaks, without added toxicity that prevents patients completing a full course of treatment.","rationale":"177Lu-PSMA-617 predominantly causes DNA single-strand breaks repaired via PARP-dependent base excision repair; PARP inhibition is mechanistically expected to radiosensitise tumour cells by blocking this repair. The LuPARP phase 1 trial found the combination tolerable across ten olaparib dosing schedules with no dose-limiting toxicities, and reported PSA50 62% and PSA90 48% in an interim analysis of heavily pretreated patients, with median radiographic progression-free survival of 12.8 months at the recommended phase 2 dose — figures that compare favourably with historical 177Lu-PSMA-617 monotherapy series, though this was a single-arm study without a concurrent comparator.","test":"LuPARP (NCT03874884) has already generated phase 1 safety and preliminary activity data in a single-arm design; the next step is a randomised phase 2/3 trial of 177Lu-PSMA-617 with or without olaparib in metastatic castration-resistant prostate cancer, powered on radiographic progression-free survival, alongside the ongoing alpha-emitter analogue trial of FPI-2265 plus olaparib (NCT06909825).","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5,"route":"/ideas/idea-rlt-plus-parp-inhibitor/"}
{"id":"idea-rlt-plus-checkpoint-inhibitor","kind":"idea","name":"Adding a checkpoint inhibitor to PSMA radioligand therapy","aka":[],"tldr":"Radiation from a targeted radioactive treatment can spill tumour debris that alerts the immune system. Giving an immunotherapy drug at the same time, to stop the immune system being switched off, is being tested to see if it makes the radioactive treatment work better.","summary":"Radiation-induced cell death can expose tumour antigens and trigger immune responses, but immune checkpoints such as PD-1 can suppress that response. The PRINCE trial (NCT03658447, Peter MacCallum Cancer Centre) tested whether adding the PD-1 inhibitor pembrolizumab to 177Lu-PSMA-617 could improve outcomes in metastatic castration-resistant prostate cancer, a disease in which checkpoint inhibitors alone have limited activity. In this single-arm phase 1b/2 study of 37 patients, up to six cycles of 177Lu-PSMA-617 were given with pembrolizumab every three weeks for up to 24 months. The trial reported a PSA50 response rate of 76% and PSA90 of 46%, notably higher than the roughly 46% (VISION) and 66% (TheraP) PSA50 rates reported with 177Lu-PSMA-617 alone in other trials, and median radiographic progression-free survival of 11.2 months with median overall survival of 17.8 months.\n\nThe combination was not free of added toxicity: 35% of patients experienced grade 3 treatment-related adverse events, including grade 3 immune-related events in 30% of patients (colitis, myasthenia gravis, acute kidney injury, oral mucositis among them), and 14% of patients discontinued pembrolizumab because of immune-related toxicity, though all patients were able to continue 177Lu-PSMA-617. Because PRINCE was single-arm with no concurrent comparator, the reported PSA response rates cannot be directly attributed to the addition of pembrolizumab rather than to differences in patient selection between trials. A second combination trial, testing the CTLA-4-directed antibody ONC-392 alongside 177Lu-PSMA-617 (NCT05682443), is exploring an alternative checkpoint target in the same disease setting.","asOf":"2026-09-22","links":[{"label":"177Lu-PSMA-617 in combination with pembrolizumab for treatment of mCRPC (PRINCE): phase 1b/2 study (PubMed, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/41926961/"},{"label":"PRINCE trial 12-month follow-up results (ASCO abstract, 2025)","url":"https://www.asco.org/abstracts-presentations/ABSTRACT383277"},{"label":"Lu-PSMA-617/Pembrolizumab Shows Early Efficacy in Metastatic CRPC (Cancer Network, summary of Lancet Oncology publication)","url":"https://www.cancernetwork.com/view/lu-psma-617-pembrolizumab-shows-early-efficacy-in-metastatic-crpc"},{"label":"PRINCE study (ClinicalTrials.gov, NCT03658447)","url":"https://clinicaltrials.gov/study/NCT03658447"}],"tags":["combination therapy","immunotherapy","prostate"],"related":["pluvicto","pembrolizumab","sandhu-shahneen","prostate-mcrpc","vision","therap","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combining lutetium-177-PSMA-617 with the PD-1 inhibitor pembrolizumab will produce a higher PSA response rate in metastatic castration-resistant prostate cancer than radioligand therapy alone, by exposing radiation-released tumour antigens to an immune system no longer blocked by PD-1 signalling.","rationale":"The single-arm PRINCE trial (37 patients) reported a PSA50 response rate of 76% and PSA90 of 46%, higher than the 46% (VISION) and 66% (TheraP) PSA50 rates reported for 177Lu-PSMA-617 monotherapy in other trials, but with no concurrent comparator arm the apparent improvement could reflect differences in patient selection rather than a true treatment effect. The trial also documented a meaningful immune-related toxicity burden, with 30% of patients experiencing grade 3 immune-related adverse events and 14% discontinuing pembrolizumab.","test":"A randomised phase 2 or 3 trial directly comparing 177Lu-PSMA-617 plus pembrolizumab against 177Lu-PSMA-617 alone in PSMA-positive metastatic castration-resistant prostate cancer, powered on PSA50 response rate or radiographic progression-free survival, roughly 150-250 patients, to confirm or refute the single-arm PRINCE signal and quantify the added immune-related toxicity against any efficacy gain.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5,"route":"/ideas/idea-rlt-plus-checkpoint-inhibitor/"}
{"id":"idea-neoadjuvant-psma-therapy","kind":"idea","name":"Neoadjuvant PSMA radioligand therapy before prostatectomy","aka":[],"tldr":"For men with high-risk prostate cancer that hasn't spread yet, giving a dose or two of PSMA-targeted radioactive treatment before surgery, rather than only using it after the cancer has spread, might kill hidden cancer cells surgery alone would miss. It is still experimental and hasn't yet been shown to help patients live longer or avoid the cancer coming back.","summary":"Lutetium-177-PSMA-617 is approved for metastatic castration-resistant prostate cancer, but its combination of tumour-targeted radiation and imageable gamma emission has prompted interest in moving it earlier, to localised high-risk disease, on the theory that it could eliminate occult micrometastases before they become detectable. The LuTectomy trial (NCT04430192, Peter MacCallum Cancer Centre) tested this in 20 men with high-risk localised prostate cancer and high PSMA expression on PSMA PET, giving one cycle (10 patients) or two cycles (10 patients) of approximately 5 GBq 177Lu-PSMA-617 six weeks before robotic radical prostatectomy. The trial delivered a median tumour absorbed dose of 35.5 Gy across all lesions (19.6 Gy to the prostate), was well tolerated with no grade 3/4 toxicity, and did not compromise surgical safety; 45% of patients achieved a 50% or greater PSA decline, and 80% showed a partial histological response (stromal fibrosis, reduced tumour cell density), but no patient achieved a pathological complete response with a single or double cycle.\n\nBecause monotherapy did not achieve pathological complete responses, follow-on trials are testing combinations and longer regimens. The German NEPI trial (randomised, EudraCT 2021-004894-30, 46 patients) is comparing androgen deprivation therapy plus two cycles of 177Lu-PSMA-617 with or without the checkpoint inhibitor ipilimumab, with pathological complete response as a co-primary endpoint. In the United States, the PRELUDE trial (NCT06798558, Hackensack University Medical Center and others) is a phase 2 study giving two cycles of 177Lu-PSMA-617 before prostatectomy and following patients for two years for biochemical recurrence.\n\nNo trial has yet reported a survival, metastasis-free survival, or biochemical-recurrence benefit from this strategy, and neoadjuvant radioligand therapy is not recommended by any current guideline; a 2025 review explicitly states the approach 'does not yet have data to support any benefit' in these harder outcomes and remains investigational.","asOf":"2026-09-22","links":[{"label":"Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy (LuTectomy): phase 1/2 study (European Urology, PubMed 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/37891072/"},{"label":"Neoadjuvant 177Lutetium-PSMA-617 Radioligand Therapy for High-Risk Prostate Cancer (review, PMC 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12563130/"},{"label":"Lu-177-PSMA-617 before Radical Prostatectomy (PRELUDE) (NCI trial listing, NCT06798558)","url":"https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-04728"}],"tags":["neoadjuvant","prostate","surgery"],"related":["pluvicto","prostate-high-risk","prostatectomy","idea-psma-pet-guided-mdt","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Giving one or two cycles of lutetium-177-PSMA-617 before radical prostatectomy in men with high-risk localised prostate cancer will reduce micrometastatic disease burden and improve long-term biochemical-recurrence-free survival compared with prostatectomy alone, without making surgery less safe.","rationale":"The LuTectomy trial demonstrated that neoadjuvant 177Lu-PSMA-617 delivers substantial targeted radiation dose (median 35.5 Gy to lesions) with minimal toxicity and no impairment of surgical safety, and produced partial histological responses in 80% of patients, but achieved zero pathological complete responses with up to two cycles, showing monotherapy alone is probably insufficient. Whether the observed PSA declines and histological changes translate into fewer biochemical recurrences or better long-term survival is unverified; a 2025 review states this explicitly.","test":"The randomised NEPI trial (EudraCT 2021-004894-30, 46 patients), testing androgen deprivation plus 177Lu-PSMA-617 with or without ipilimumab with pathological complete response as a co-primary endpoint, and the US phase 2 PRELUDE trial (NCT06798558) following patients for two-year biochemical recurrence, are the next steps toward establishing whether this strategy has a genuine oncological benefit; a phase 3 trial with metastasis-free or overall survival as the primary endpoint would be required to change practice.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":8,"route":"/ideas/idea-neoadjuvant-psma-therapy/"}
{"id":"idea-accelerator-ac225-at-scale","kind":"idea","name":"Scaling actinium-225 supply with proton accelerators instead of the thorium-229 cow","aka":[],"tldr":"Most of the world's actinium-225, a rare radioactive metal used in some newer cancer treatments, comes from slowly extracting it from an old stockpile of another radioactive element. A different method — firing high-energy protons at ordinary thorium metal in an accelerator — can make much bigger batches, needed if actinium-225 treatments are ever to reach more than a small number of patients.","summary":"Historically, essentially all of the world's actinium-225 has come from 'milking' a legacy stockpile of thorium-229 (itself derived from uranium-233), a process that yields only about 1-1.2 curies a year worldwide, enough for roughly 1,000-1,200 patients and far too little to run more than the most preliminary clinical trials. The US Department of Energy's Isotope Program established the Ac-225 Tri-Lab Effort in 2014-2015 across Brookhaven, Los Alamos and Oak Ridge National Laboratories to develop an alternative: firing high-energy (greater than 70 MeV) proton beams at thorium-232 targets to produce actinium-225 by spallation, a reaction that does not depend on the finite thorium-229/uranium-233 stockpile.\n\nIn June 2021, Brookhaven demonstrated that this accelerator route could generate about 60% of the entire annual thorium-229-derived supply in a single 12-day irradiation and processing campaign. The FDA accepted a Type II Drug Master File for accelerator-produced actinium-225 nitrate from Oak Ridge National Laboratory in January 2020, and the Tri-Lab effort has since distributed more than 1,100 millicuries of accelerator-produced actinium-225 to evaluators, with batch sizes targeted to grow from the historical 50-100 mCi range toward 100-1,000 mCi per batch. Brookhaven completed an $8.5 million refurbishment of its All-Purpose Hot Cell facility in March 2023 specifically to expand actinium-225 processing capacity, and separately NorthStar Medical Radioisotopes has pursued a different accelerator route (electron-beam photonuclear transmutation of radium-226) intended to produce up to 200 curies a year per accelerator.\n\nA known trade-off of the proton-spallation route is co-production of actinium-227, a long-lived (22-year) alpha emitter; the DOE Isotope Program states this is kept to 2% or less of total activity at product release, and held a joint roundtable with the US Nuclear Regulatory Commission in March 2023 to work through the regulatory implications of that impurity for hospitals and clinics using the material.","asOf":"2026-09-22","links":[{"label":"Production Methods for Ac-225 (DOE Isotope Program)","url":"https://www.isotopes.gov/information/actinium-225"},{"label":"Tri-Lab effort makes strides toward increasing supply of Ac-225 (ORNL news, 2021)","url":"https://www.ornl.gov/news/tri-lab-effort-makes-strides-toward-increasing-supply-ac-225-0"},{"label":"Streamlined Actinium-225 Processing through new All-Purpose Hot Cells (DOE Isotope Program, 2023)","url":"https://isotopes.gov/BNL-AP-Hot-Cells"},{"label":"Accelerating Production of Non-Carrier Added Actinium-225 (NorthStar technical report)","url":"https://www.northstarnm.com/wp-content/uploads/2023/11/Accelerating-Production-of-Non-Carrier-Added-Actinium-225-n.c.a.-Ac-225.pdf"},{"label":"DOE Isotope Program virtual roundtable with NRC on accelerator-produced Ac-225","url":"https://isotopes.gov/NRC-roundtable"}],"tags":["isotope supply","actinium-225","manufacturing"],"related":["actinium-225-supply","northstar-medical-radioisotopes","idea-reg-ac225-accelerator-pharmacopoeia","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Producing actinium-225 by proton-beam spallation of thorium-232 in linear accelerators, rather than extracting it from the legacy thorium-229 stockpile, can scale world supply from roughly 1-1.2 curies a year to the hundreds-of-curies scale needed for large randomized trials and eventual commercial radioligand therapy.","rationale":"The DOE Tri-Lab effort demonstrated in 2021 that a single 12-day accelerator campaign could produce about 60% of the entire annual thorium-229-derived supply, and the FDA has already accepted a Drug Master File for the accelerator-produced material, showing the regulatory pathway is viable. The main open questions are whether batch sizes can be sustained at the 100-1,000 mCi scale needed for a registrational trial, and how regulators and clinics will handle the co-produced, long-lived actinium-227 impurity.","test":"The 2021 Brookhaven demonstration campaign already showed technical feasibility at scale; the next milestone is whether the renovated Brookhaven All-Purpose Hot Cell facility and expanded Los Alamos target capacity sustain routine batches in the hundreds of millicuries, and whether an actinium-225 radioligand therapy programme can complete a registrational trial supplied entirely from accelerator-produced material under an agreed actinium-227 impurity limit.","maturity":"being-tested-at-scale","actor":"engineering","cost":"large","horizonYears":5,"route":"/ideas/idea-accelerator-ac225-at-scale/"}
{"id":"idea-regional-radiopharmacy-network","kind":"idea","name":"In-house hospital radiopharmacy compounding to cut dose waste","aka":[],"tldr":"Radioactive treatments lose strength every day as they travel from a central factory to the hospital, so by the time a dose arrives some of its power has decayed away. Installing compact, automated dose-preparation equipment inside individual hospitals, so they compound the treatment themselves from bulk material, could cut that wasted radioactivity and get treatment to more places.","summary":"Lutetium-177 decays with a roughly 6.6-day half-life, so every day a finished dose spends in transit from a centralised commercial manufacturer to a treating hospital is activity permanently lost, and the further a treatment centre is from that manufacturer, the more waste and scheduling risk it faces. An alternative model is for individual hospitals to compound doses themselves from bulk shipments of the raw isotope, using compact automated synthesis units designed to fit inside an existing hospital radiopharmacy hood. A 2025 paper describes one such unit, 'MiniLu', a cassette-based, self-contained radiosynthesis platform that achieved greater than 99% radiochemical purity and about 95% final dose yield for two PSMA-targeting therapeutic ligands, explicitly designed for hospital-resident compounding rather than centralised manufacturing.\n\nThis decentralisation is already happening at small scale in some markets: a 2026 market analysis reports that hospital radiopharmacy units in Mexico City, Monterrey and Guadalajara have grown from an estimated 3-5 to 8-12 sites capable of onsite GMP labelling since 2022, explicitly to reduce logistical waste from short-half-life lutetium-177, with domestically compounded lutetium-177 dotatate capturing an estimated 20-30% of treatment volume in that market. The joint EANM/SNMMI/IAEA guide to setting up a theranostics centre documents the radioactive-material licensing and radiation-safety steps a hospital needs to run in-house compounding.\n\nThis is a narrower, single-institution version of the regional cyclotron-hub policy idea already in this graph (a national or multi-country network of shared hubs); this idea is specifically about individual hospitals building their own point-of-care compounding capability, which trades a larger upfront capital and licensing cost per site for less dependence on shipping schedules and less decay-related waste. No controlled study quantifying the waste or access benefit of this decentralised model over centralised commercial dose manufacturing was found.","asOf":"2026-09-22","links":[{"label":"Optimization of the radiosynthesis of PSMA-targeting drugs using a cassette-based platform (MiniLu) (PMC, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12623512/"},{"label":"Peptide Receptor Radionuclide Therapy (PRRT) Market in Mexico (IndexBox market report, 2026)","url":"https://www.indexbox.io/store/mexico-peptide-receptor-radionuclide-therapy-prrt-market-analysis-forecast-size-trends-and-insights/"},{"label":"Joint EANM, SNMMI, and IAEA Enabling Guide: How to Set up a Theranostics Center (Journal of Nuclear Medicine)","url":"https://jnm.snmjournals.org/content/63/12/1836"},{"label":"The growth of radiotherapeutics: Addressing supply chain complexity (pharmaphorum, 2026)","url":"https://pharmaphorum.com/rd/growth-radiotherapeutics-addressing-supply-chain-complexity"}],"tags":["radiopharmacy","supply chain","access"],"related":["idea-reg-regional-radiopharmacy-hubs","radiopharmacy-network","radiopharmaceutical-gmp-release","therapy-isotope-supply-chain","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Installing automated, hospital-resident radiopharmacy compounding units that prepare short-half-life doses (lutetium-177 or actinium-225 ligands) on demand from bulk isotope shipments will reduce dose waste from radioactive decay in transit and improve treatment access outside major metropolitan centres, compared with relying solely on centralised commercial dose manufacturing and next-day shipping.","rationale":"A described automated cassette-based synthesis unit ('MiniLu') demonstrates that hospital-hood-compatible, hospital-resident compounding of lutetium-177 PSMA ligands can achieve greater than 99% purity and about 95% yield, comparable to centralised manufacturing. Market data from Mexico show hospital radiopharmacy sites capable of onsite GMP labelling roughly doubling since 2022, explicitly to reduce Lu-177 decay waste, and now handling an estimated 20-30% of treatment volume in that market — real-world evidence the model is being adopted, though no controlled comparative study of waste reduction or access improvement was found.","test":"A controlled before/after study across a multi-site hospital system, comparing dose waste (activity discarded to decay or scheduling failures), turnaround time and patient access (drive time to nearest treatment site) before and after installing in-house automated compounding units at 3-5 hospitals, against a comparable set of hospitals continuing to rely on centralised commercial dose supply.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":7,"route":"/ideas/idea-regional-radiopharmacy-network/"}
{"id":"idea-total-body-pet-lower-dose-tracers","kind":"idea","name":"Using total-body PET's sensitivity to cut diagnostic tracer dose, not just scan time","aka":[],"tldr":"New whole-body scanners are so much more sensitive than standard PET machines that they can produce a clear picture using a small fraction of the usual radioactive tracer dose. Most of that extra sensitivity has been used to make scans faster; using it instead to lower the radiation dose given to patients and staff is a separate, less-explored option.","summary":"Total-body PET scanners such as the uEXPLORER and PennPET Explorer cover roughly 194 cm of the body in one bed position, versus 15-35 cm for conventional PET, giving them a reported 40-fold gain in overall sensitivity. That extra sensitivity is most often spent on shortening scan time or improving image quality at a standard tracer dose, but it can equally be spent on reducing the injected activity while keeping scan time and image quality constant, which lowers radiation dose to the patient and to staff handling the syringe.\n\nEvidence for the dose-reduction use case exists but is still limited in scale. Phantom studies on the uEXPLORER found contrast recovery for FDG images was preserved down to about 30% of standard injected activity, and healthy volunteers have been imaged with diagnostic-quality results at doses as low as 14.8-25 MBq (roughly 0.4-0.7 mCi), around 5% of a typical 10-20 mCi clinical FDG dose. A retrospective single-centre study of 88 patients with hepatic malignancies found that a tenfold reduction in injected FDG activity (about 0.37 MBq/kg versus the standard 3.7 MBq/kg) produced comparable kinetic and static image quality in both dynamic and static imaging. Total-body PET has also been used to image 68Ga-DOTATATE at roughly one-fifth of the standard clinical dose in at least one reported case, which is relevant given ongoing global gallium-68 generator supply constraints.\n\nThis is a distinct proposal from the existing total-body-PET-for-dosimetry idea in this graph, which uses total-body PET's whole-body coverage to personalise therapeutic radioligand dosing; this idea is specifically about lowering the injected activity of diagnostic tracers such as FDG, PSMA or somatostatin-receptor agents while keeping diagnostic accuracy unchanged. No large, prospective, blinded, multi-reader diagnostic-accuracy trial comparing standard-dose against substantially dose-reduced total-body PET has been reported.","asOf":"2026-09-22","links":[{"label":"Total Body PET: Why, How, What for? (PMC review)","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595297/"},{"label":"One-tenth-activity total-body PET versus full-activity imaging in hepatic malignancies (QIMS, 2023)","url":"https://qims.amegroups.org/article/view/118297/html"},{"label":"Total-body PET/CT — first clinical experiences and future perspectives (eScholarship, UCSF/UC Davis)","url":"https://escholarship.org/content/qt1wx8761n/qt1wx8761n_noSplash_6eb388d1960fed7f031a438777911ba9.pdf"}],"tags":["total-body PET","dose reduction","imaging"],"related":["idea-total-body-pet-dosimetry","total-body-pet-screening","nuclear-medicine-hardware","fdg-pet","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Total-body PET's roughly 40-fold sensitivity gain over conventional PET can be used to cut injected diagnostic tracer activity by 90% or more while preserving diagnostic image quality and lesion detection, reducing radiation dose to patients and staff, rather than being used only to shorten scan duration.","rationale":"Phantom and retrospective clinical studies on the uEXPLORER total-body PET scanner show preserved contrast recovery and comparable kinetic/static image quality at 70-90% reductions in injected FDG activity, and diagnostic-quality images have been produced in healthy volunteers at roughly 5% of a standard clinical FDG dose. These findings are from phantom evaluations and single-centre retrospective series rather than prospective, blinded, multi-reader diagnostic-accuracy comparisons, so the clinical reliability of very-low-dose protocols for lesion detection in a general oncology population is not yet established.","test":"A prospective, multi-reader, blinded diagnostic-accuracy study in which the same patients undergo total-body PET/CT at both standard and substantially reduced (for example 90% lower) injected activity, scored independently for lesion detection and reader confidence against a reference standard, in roughly 50-100 patients undergoing routine FDG oncology staging.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":5,"route":"/ideas/idea-total-body-pet-lower-dose-tracers/"}
{"id":"idea-bispecific-radioligands","kind":"idea","name":"Bispecific PSMA/GRPR radioligands for discordant prostate cancer lesions","aka":[],"tldr":"Not every prostate cancer cell carries the same marker: some show the PSMA protein that most scans target, others show a different marker called GRPR instead. A single tracer molecule built to stick to both markers at once could find and treat tumours that a PSMA-only or GRPR-only scan would miss.","summary":"PSMA and GRPR expression in prostate cancer are complementary rather than fully overlapping: GRPR tends to be higher in earlier, lower-grade disease and PSMA in more advanced disease, and a head-to-head comparison of 68Ga-PSMA-11 and 68Ga-RM2 (a GRPR ligand) PET found broadly similar overall detection rates but each tracer found lesions the other missed. This has motivated development of bispecific 'heterodimer' molecules that carry both a PSMA-binding urea-based inhibitor and a GRPR-binding bombesin-analogue peptide on a single scaffold, so that a lesion expressing either receptor (or both) would be detected or treated.\n\nSeveral such heterodimers have been synthesised and tested in mouse models. A DUPA-RM26 heterodimer (NOTA-DUPA-RM26) showed high affinity and specific binding to both PSMA-positive and GRPR-positive cell lines with only moderate affinity loss compared with the individual monomers; a related iPSMA-BN heterodimer reached a first-in-human PET imaging study reporting specific uptake in the pancreas (GRPR-expressing) and salivary glands (PSMA-expressing) of healthy volunteers; and a 2024 paper reported a DOTA-conjugated heterodimer combining PSMA-617 and the GRPR antagonist RM2, labelled with both gallium-68 and lutetium-177, which showed dual-receptor tumour targeting, faster pharmacokinetics and lower kidney uptake than either parent compound alone in mouse xenografts.\n\nDespite this preclinical progress, two independent reviews (2020 and 2025) both state that none of the described PSMA/GRPR bispecific radioligands has yet been evaluated in a clinical trial in patients; the concept remains preclinical, distinct from the closely related but separately developed GRPR-only and PSMA-only radioligands already in clinical use or trials.","asOf":"2026-09-22","links":[{"label":"Bispecific Radioligands (BRLs): Two Is Better Than One (PMC review, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12386959/"},{"label":"Current State of Radiolabeled Heterobivalent Peptidic Ligands in Tumor Imaging and Therapy (MDPI review, 2020)","url":"https://www.mdpi.com/1424-8247/13/8/173"},{"label":"Synthesis and Preclinical Evaluation of a Bispecific PSMA-617/RM2 Heterodimer (PMC, 2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11571012/"},{"label":"Gastrin Releasing Peptide Receptors-targeted PET imaging in prostate cancer (Erasmus MC review)","url":"https://pure.eur.nl/ws/portalfiles/portal/150811942/1-s2.0-S1556859824000191-main.pdf"}],"tags":["bispecific","prostate","molecular imaging"],"related":["psma","grpr","psma-pet","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single small-molecule radioligand that binds both PSMA and GRPR will detect and, in a therapeutic form, treat more prostate cancer lesions than a PSMA-only or GRPR-only agent, because it captures tumours regardless of which receptor they predominantly express, including cases with discordant single-tracer PET results.","rationale":"PSMA and GRPR expression patterns in prostate cancer are complementary across disease stages, and a head-to-head PET comparison found each single-target tracer detected lesions the other missed, supporting the rationale for a dual-target agent. Multiple PSMA/GRPR heterodimers have shown dual-receptor binding, tumour uptake and favourable biodistribution in mouse xenograft models, including one first-in-human imaging study of a related heterodimer in healthy volunteers, but two independent reviews confirm that no PSMA/GRPR bispecific radioligand has yet been tested in cancer patients.","test":"A first-in-human phase 0/1 imaging study of a PSMA/GRPR bispecific PET tracer in patients with biochemically recurrent prostate cancer and known discordant single-tracer PSMA and GRPR PET results, roughly 20-30 patients, comparing lesion detection rate against same-patient single-target PSMA and GRPR PET scans, as the precursor step before testing a therapeutic bispecific ligand.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":9,"route":"/ideas/idea-bispecific-radioligands/"}
{"id":"idea-copper-theranostic-pair-standard","kind":"idea","name":"A single-molecule copper-64/copper-67 pair instead of switching ligands between scan and treatment","aka":[],"tldr":"Most PSMA treatments use one molecule to take the pre-treatment scan and a slightly different molecule for the actual treatment, so the scan is only an approximate guide. A copper-based pair uses the identical molecule for both steps, just with a different form of copper, so the scan should be a much truer preview of where the treatment radiation will go.","summary":"The standard PSMA theranostic workflow images patients with 68Ga-PSMA-11 or a related diagnostic ligand and then treats responders with 177Lu-PSMA-617, a chemically different molecule; differences in the two ligands' binding and pharmacokinetics mean the diagnostic scan is only an approximate predictor of the therapeutic biodistribution. Clarity Pharmaceuticals' SAR-bisPSMA programme instead uses one identical molecule labelled with two isotopes of the same element: copper-64 for PET imaging and copper-67 for beta-emitting therapy, so in principle the diagnostic scan should be a much closer match to the therapeutic distribution than a cross-ligand, cross-element approach.\n\nThe combination is being tested in the ongoing SECuRE trial (NCT04868604), a US multi-centre, single-arm phase I/IIa study in metastatic castration-resistant prostate cancer, aiming to enrol approximately 54 participants. Company-reported interim results (data cut-off 20 July 2026) from 19 participants treated at the 8 GBq 67Cu-SAR-bisPSMA dose level showed a PSA50 response rate of 63% and PSA90 of 26%, with 81% of radiographically evaluable participants achieving disease control, including 31% with a complete response or undetectable disease by RECIST, bone scan or PSA; no dose-limiting toxicities have been reported across dose-escalation cohorts up to 12 GBq, and the sponsor states registrational phase 3 planning is under way.\n\nThese results come from company press releases and conference-style updates rather than an independent peer-reviewed publication, and the trial is a single-arm study, so there is no direct comparison yet against 177Lu-PSMA-617 or another PSMA radioligand therapy to establish whether the same-molecule imaging/therapy matching translates into a measurable clinical advantage over the established gallium-68/lutetium-177 approach.","asOf":"2026-09-22","links":[{"label":"SECuRE update: 8 GBq Cu-67 SAR-bisPSMA dose level results (Clarity Pharmaceuticals, Aug 2026)","url":"https://www.claritypharmaceuticals.com/news/secure-update-05-08-26/"},{"label":"SECuRE trial update: another participant with undetectable disease (Clarity Pharmaceuticals, Feb 2026)","url":"https://www.claritypharmaceuticals.com/news/secure-undetectable/"},{"label":"64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA (SECuRE) (ClinicalTrials.gov, NCT04868604)","url":"https://clinicaltrials.gov/study/NCT04868604"}],"tags":["copper theranostics","prostate","same-molecule imaging"],"related":["nct04868604","psma","prostate-mcrpc","pluvicto","ga-68","cu-64","lu-177","cu-67"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Using the identical molecule for imaging (copper-64) and therapy (copper-67) in PSMA-targeted treatment, rather than switching between different ligands such as gallium-68-PSMA-11 for imaging and lutetium-177-PSMA-617 for therapy, will give a more accurate match between the pre-therapy scan and the actual therapeutic radiation distribution, improving patient selection and predicting toxicity more reliably.","rationale":"Because 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA are the same molecule differing only in the copper isotope, the pre-therapy scan should in principle predict the therapeutic biodistribution more directly than the common practice of imaging with one ligand and treating with a different one. Interim company-reported results from the SECuRE trial (19 participants at the 8 GBq dose level) show promising PSA response and radiographic disease-control rates with no observed dose-limiting toxicity, but these are sponsor-reported interim data from a single-arm trial, not an independent peer-reviewed head-to-head comparison against 177Lu-PSMA-617.","test":"The ongoing SECuRE trial itself (NCT04868604, approximately 54 planned participants) reporting mature, independently peer-reviewed phase II data, followed by a randomised phase 3 (registrational planning reported by the sponsor as under way) comparing 67Cu-SAR-bisPSMA against 177Lu-PSMA-617 or standard of care in metastatic castration-resistant prostate cancer.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":6,"route":"/ideas/idea-copper-theranostic-pair-standard/"}
{"id":"idea-alpha-for-oligometastatic-disease","kind":"idea","name":"Alpha-emitting PSMA therapy for oligometastatic (few-lesion) prostate cancer","aka":[],"tldr":"When prostate cancer comes back in just a handful of spots, doctors already zap those spots with precision radiotherapy. Adding a single dose of an alpha-particle radioactive drug at the same time, instead of the more established beta-particle version, might mop up cancer cells too small to see on a scan, because alpha radiation travels a much shorter distance and hits harder in that short range.","summary":"Oligorecurrent prostate cancer, typically defined as one to five metastatic lesions visible on PSMA PET after initial treatment, is increasingly treated with metastasis-directed stereotactic body radiotherapy (SBRT) to the visible spots, sometimes combined with a radioligand. Beta-emitting 177Lu-PSMA-I&T has already been tested as monotherapy in this setting: the randomised BULLSEYE trial (NCT04443062, 58 patients) compared two cycles of 177Lu-PSMA-I&T against standard-of-care deferred hormone therapy in oligometastatic hormone-sensitive disease. Alpha emitters have a much shorter particle range (tens to about 100 micrometres versus roughly a millimetre for lutetium-177's beta particles), which is physically well suited to killing scattered single cells or micrometastases invisible on the pre-treatment scan, but this physical argument has not yet been tested head-to-head against beta therapy in oligometastatic disease.\n\nThat direct comparison is now the subject of an open randomised trial: ANDROMEDA (NCT07150715, UCLA, led by Amar Kishan) randomises patients with one to five oligorecurrent lesions to either two cycles of 177Lu-PSMA-617 plus SBRT or a single cycle of 225Ac-PSMA-617 plus SBRT, with progression-free survival at 24 months (defined by PSMA PET/CT or biochemical progression) as the primary comparison. Separately, the ACCEL trial (NCT06229366) is testing a next-generation alpha ligand, 225Ac-PSMA-62 (LY4181530), specifically designed with a different linker to reduce the xerostomia and marrow toxicity associated with first-generation 225Ac-PSMA-617 or 225Ac-PSMA-I&T, in both oligometastatic hormone-sensitive and castration-resistant cohorts.\n\nNo trial has yet reported a comparative result between alpha- and beta-emitter approaches in oligometastatic disease; the rationale rests on radiobiological principles and on a strong first-generation alpha-emitter side-effect profile (particularly xerostomia) that newer ligands like PSMA-62 aim to address.","asOf":"2026-09-22","links":[{"label":"ANDROMEDA: Alpha- or Beta-Emitting Radionuclide With Metastasis-Directed SBRT for Recurrent Oligometastatic Prostate Cancer (ClinicalTrials.gov, NCT07150715)","url":"https://clinicaltrials.gov/study/NCT07150715"},{"label":"ANDROMEDA (NCI trial listing)","url":"https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-05583"},{"label":"ACCEL: Ac-225-PSMA-62 phase Ia/Ib/II trial in oligometastatic and castration-resistant prostate cancer (ASCO abstract, 2025)","url":"https://ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS282"},{"label":"Lutetium-177-PSMA-I&T as metastases-directed therapy in oligometastatic hormone-sensitive prostate cancer (BULLSEYE, BMC Cancer, 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7490874/"}],"tags":["alpha therapy","oligometastatic","prostate"],"related":["ac225-psma","pluvicto","oligometastatic","idea-psma-pet-guided-mdt","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Treating oligometastatic (one-to-five lesion) recurrent prostate cancer with a single dose of an alpha-emitting PSMA radioligand alongside stereotactic body radiotherapy to each visible lesion will control disease for longer than the same regimen using the beta-emitter lutetium-177-PSMA-617, because the alpha particle's short range concentrates a lethal dose in micrometastases that are below the resolution of the pre-treatment scan.","rationale":"The rationale is grounded in the established physical difference between alpha and beta emitters (alpha's roughly 100-micron range is a better physical match for single cells and micrometastases than beta's roughly 1 mm range), but no completed clinical trial has yet compared the two approaches in oligometastatic disease. The randomised ANDROMEDA trial (NCT07150715) is specifically designed to test this comparison directly, and the BULLSEYE trial already established that beta-emitter 177Lu-PSMA-I&T monotherapy alone can be tested against standard of care (deferred androgen deprivation) in this setting, providing the methodological precedent.","test":"ANDROMEDA (NCT07150715), an open, randomised phase 2 trial at UCLA comparing two cycles of 177Lu-PSMA-617 plus SBRT against a single cycle of 225Ac-PSMA-617 plus SBRT in patients with one to five oligorecurrent lesions, with 24-month progression-free survival (by PSMA PET/CT or biochemical progression) as the primary comparison.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6,"route":"/ideas/idea-alpha-for-oligometastatic-disease/"}
{"id":"idea-fap-theranostics-sarcoma","kind":"idea","name":"FAP-targeted radioligand therapy for sarcoma","aka":[],"tldr":"Sarcomas, a group of rare and hard-to-treat cancers, often carry a marker called FAP not just on the supporting tissue around the tumour but on the cancer cells themselves. A radioactive drug built to find FAP is being tried as a treatment, but the small studies done so far disagree about whether it actually shrinks tumours.","summary":"Fibroblast activation protein (FAP) is usually found on the stromal cells surrounding a tumour rather than on cancer cells directly, which limits how selective a FAP-targeted therapy can be, but sarcomas are one of the few cancer types where the tumour cells themselves can express FAP. 68Ga-FAPI PET has shown superior lesion detection compared with 18F-FDG PET across multiple sarcoma subtypes in prospective imaging cohorts, making FAP an attractive target for a therapeutic radioligand in a disease with essentially no PSMA or somatostatin-receptor expression to exploit.\n\nThe handful of early-phase therapeutic studies published so far give a mixed signal. A 5-patient pilot study of 177Lu-FAPI-2286 in metastatic sarcoma reported partial response in 4 of 5 patients by RECIST, with a 52% mean reduction in primary tumour volume. A separate, later 6-patient exploratory study of the same drug in metastatic sarcoma found no RECIST partial or complete responses at all, only stable disease in some patients (with mixed results by other volumetric metrics), a median overall survival of just 4 months, and 3 of 6 patients dying during follow-up. A first-in-human dose-escalation trial of a related FAP ligand, 177Lu-FAPI-XT (NCT06211647/NCT06197139, 14 patients across several tumour types including fibroblastic sarcoma subtypes), found an overall disease control rate of 35.7%, rising to 50% in the sarcoma subtypes specifically, but no complete or partial responses in the whole cohort, alongside a favourable safety profile with no dose-limiting toxicity up to 11.1 GBq. Separately, the Novartis-sponsored LuMIERE trial (NCT04939610) is testing 177Lu-FAP-2286 in pancreatic, non-small-cell lung and breast cancer, not specifically in sarcoma.\n\nThese are all small, uncontrolled, single-arm case series (5-14 patients each) with conflicting response rates, so whether FAP-targeted radioligand therapy has genuine, reproducible activity in sarcoma, and if so in which histological subtypes, remains unresolved.","asOf":"2026-09-22","links":[{"label":"Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma (EJNMMI, 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39060377/"},{"label":"Safety and efficacy of 177Lu-FAPI-XT radioligand therapy in advanced sarcoma and other cancer entities: first-in-human, dose-escalation study (EJNMMI, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/41087606/"},{"label":"Theranostics in Sarcoma: A Critical Review of Current Evidence and Future Directions (2026 review)","url":"https://link.springer.com/content/pdf/10.1007/s11864-026-01386-0.pdf"},{"label":"A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE) (ClinicalTrials.gov, NCT04939610)","url":"https://clinicaltrials.gov/study/NCT04939610"}],"tags":["FAP","sarcoma","theranostics"],"related":["fap","fap-2286","fapi-pet","idea-fap-theranostics-pancancer","f-18","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Because sarcoma tumour cells, unlike most other cancers, can themselves express fibroblast activation protein, targeting FAP with a therapeutic radioligand will produce meaningful and reproducible disease control in advanced sarcoma, a cancer type with almost no PSMA or somatostatin-receptor expression to exploit with existing radioligand therapies.","rationale":"68Ga-FAPI PET reliably detects more sarcoma lesions than 18F-FDG PET, establishing that FAP is a genuine, targetable marker in this disease. However, the three published or presented therapeutic case series (5, 6 and 14 patients respectively) give conflicting results: one reported 4/5 partial responses, another reported zero objective responses with a 4-month median overall survival in a similar 6-patient cohort, and a third reported disease control (mostly stable disease) in half of its sarcoma subtype patients but no objective responses at all. This inconsistency across small, uncontrolled series means the true response rate and the subtypes most likely to benefit (solitary fibrous tumour and myofibroblastic sarcoma showed the most disease control in the dose-escalation study) are not yet established.","test":"A larger, prospective phase 2 basket trial of a FAP-targeted radioligand (such as 177Lu-FAPI-2286 or 177Lu-FAPI-XT) restricted to FAP-PET-selected sarcoma patients, ideally enriched for the subtypes (solitary fibrous tumour, myofibroblastic sarcoma) that showed the most disease control in the dose-escalation series, roughly 40-60 patients, with RECIST objective response rate and progression-free survival as endpoints, to resolve the conflicting signal from the existing small case series.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":7,"route":"/ideas/idea-fap-theranostics-sarcoma/"}
{"id":"idea-ai-lesion-segmentation-dosimetry","kind":"idea","name":"AI segmentation to make voxel-level radioligand dosimetry practical at scale","aka":[],"tldr":"Working out how much radiation a patient's kidneys and tumours received after a radioactive treatment normally means a specialist spending hours tracing organ outlines by hand on a scan. Software that draws those outlines automatically using artificial intelligence can do the same job in minutes, making personalised dose tracking available everywhere, not just in a few specialist centres.","summary":"Personalised, voxel-level dosimetry after radioligand therapy requires segmenting organs and tumours on serial SPECT/CT or PET/CT scans, a step that traditionally takes a trained physicist or physician several hours per patient using manual contouring. Deep-learning segmentation models, typically convolutional neural networks such as U-Net or newer transformer architectures, have been developed to automate this step. A 2025 comparison of AI-based against fully manual kidney segmentation for single-time-point 177Lu-PSMA dosimetry, using 8 treatment cycles from 5 patients, found no statistically significant difference in mean absorbed dose between the two methods, with a Dice similarity coefficient of 0.898 between AI and manual contours, though the underlying kidney volumes did differ significantly between methods.\n\nA broader review of automated dosimetry pipelines reports that combining CNN-based organ segmentation with automated registration and dose-rate estimation can cut total per-patient processing time from 4-6 hours to 30-45 minutes, a 70-90% reduction, while achieving Dice similarity coefficients of 0.88-0.95 against expert manual contours for organ segmentation specifically. Performance for tumour lesion segmentation, as opposed to organ segmentation, is less mature: an external, held-out-centre test of an nnU-Net lesion segmentation model for PSMA PET/CT and post-therapy SPECT/CT reported lower Dice scores of 0.76-0.78, and the model's PET-derived tumour volume estimates were described as unstable in that external test.\n\nAn independent 2026 evidence review of AI in oncologic theranostics concludes that, despite this technical progress, no AI segmentation or dose-prediction model for PSMA or peptide receptor radionuclide therapy dosimetry has yet been validated in a prospective, multicentre trial demonstrating that AI-guided activity adaptation (continuing, delaying or stopping treatment based on the AI-derived dose) actually changes patient outcomes; the review explicitly calls this the priority next study for the field.","asOf":"2026-09-22","links":[{"label":"Single time-point kidney dosimetry in 177Lu-PSMA therapy: AI-based vs manual segmentation (2025)","url":"https://he01.tci-thaijo.org/index.php/bulletinAMS/article/view/279571"},{"label":"Radiomics and Artificial Intelligence in Radiotheranostics (PMC review, 2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10814892/"},{"label":"Towards Routine AI-Based PET/CT and SPECT/CT Lesion Segmentation and Tracking in PSMA Theranostics (arXiv, 2026)","url":"https://arxiv.org/abs/2603.22666"},{"label":"Artificial intelligence across oncologic theranostics: evidence review (Frontiers in Nuclear Medicine, 2026)","url":"https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2026.1935247/full"}],"tags":["artificial intelligence","dosimetry","segmentation"],"related":["radioligand-dosimetry","in-vivo-dosimetry","radiomics","mim-software","quantitative-imaging-biomarkers","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Replacing manual contouring of organs and tumours on post-therapy SPECT/CT and PET/CT with deep-learning segmentation will cut per-patient dosimetry processing time from hours to minutes without a clinically meaningful loss of accuracy, making voxel-level personalised radioligand dosing practical to run routinely rather than only in specialist research centres.","rationale":"A direct comparison of AI-based versus manual kidney segmentation for 177Lu-PSMA dosimetry found no significant difference in mean absorbed dose (p=0.964) with Dice concordance of 0.898, and a broader review reports 70-90% reductions in total processing time using automated pipelines with Dice similarity of 0.88-0.95 for organ segmentation. However, tumour lesion segmentation specifically performs less well in external testing (Dice 0.76-0.78, unstable volume estimates in one held-out-centre study), and an independent 2026 evidence review states plainly that no prospective, multicentre, decision-impact trial has yet shown AI-guided dosing actually improves outcomes.","test":"A prospective, multicentre equivalence trial comparing AI-automated against expert-manual dosimetry-guided treatment decisions (continue, delay, or stop a treatment cycle) in patients receiving 177Lu-PSMA-617 or 177Lu-DOTATATE, with the primary endpoint being agreement between the AI and manual absorbed-dose estimates against a Monte Carlo reference standard, and a secondary endpoint of agreement in the resulting clinical decision, in roughly 100-150 patients across several centres.","maturity":"being-tested-at-scale","actor":"industry","cost":"small","horizonYears":4,"route":"/ideas/idea-ai-lesion-segmentation-dosimetry/"}
{"id":"idea-open-dosimetry-data-commons","kind":"idea","name":"An open data commons linking patient-level radiopharmaceutical dosimetry to outcomes","aka":[],"tldr":"Every hospital that treats patients with radioactive drugs measures how much radiation reached the tumour and healthy organs, but this data mostly stays locked in each hospital's own files. A shared, public library pooling that dosimetry data, with patient outcomes, would let researchers everywhere build and test better dosing rules, especially smaller centres that don't see enough patients alone.","summary":"Two open resources already exist but neither covers what is missing. OpenDose is a collaboration of 18 international teams that provides freely downloadable specific absorbed fractions and S-values for 1,252 radionuclides, generated and cross-checked using six different Monte Carlo radiation-transport codes; this is foundational physics reference data (how radiation deposits in standard geometries), not patient-level dosimetry from real treatments. The Cancer Imaging Archive (TCIA), and the NCI Imaging Data Commons that ingests it alongside other sources, hosts large public collections of clinical cancer imaging, including some radiotherapy dose and structure sets, under Creative Commons licences, but there is no dedicated TCIA-style collection pairing diagnostic and post-therapy radiopharmaceutical images with per-patient organ- and tumour-absorbed-dose calculations and clinical outcomes.\n\nThe practical consequence is that dose-response findings such as the LUMEN, LUTADOSE and University of Wisconsin dosimetry series described elsewhere in this graph are each built and validated on single-centre cohorts of a few dozen patients, because no shared, pooled, patient-level dataset exists to train or externally validate a dose-response or dose-toxicity model across institutions. This also limits how AI segmentation and dose-prediction models (see the AI dosimetry idea in this graph) can be externally validated, since most reported models are trained and tested within one centre's data.\n\nNo dedicated, open, patient-level radiopharmaceutical dosimetry-and-outcomes commons was found in this research; this is an idea rather than a project already under way, distinct from the isotope-supply observatory idea already in this graph, which tracks production and shortage data rather than dosimetry-and-outcome data.","asOf":"2026-09-22","links":[{"label":"OpenDose: open-access resources for radiopharmaceutical dosimetry","url":"https://www.opendose.org/"},{"label":"OpenDose: Open-Access Resource for Nuclear Medicine Dosimetry (Journal of Nuclear Medicine, PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7539649/"},{"label":"Access the Data — The Cancer Imaging Archive (TCIA)","url":"https://www.cancerimagingarchive.net/access-data/"},{"label":"Imaging Data Commons (NCI Cancer Research Data Commons)","url":"https://datacommons.cancer.gov/repository/imaging-data-commons"}],"tags":["open data","dosimetry","data sharing"],"related":["tcia","radioligand-dosimetry","idea-reg-isotope-supply-observatory","idea-ai-lesion-segmentation-dosimetry"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared, open repository of patient-level radiopharmaceutical dosimetry data (organ and tumour absorbed doses linked to clinical outcomes, pooled across treating centres) would let smaller nuclear medicine departments and AI developers build and externally validate dose-response and dose-toxicity models that no single centre currently has enough patients to construct or test alone.","rationale":"OpenDose demonstrates that an international, multi-team collaboration can successfully build and maintain a shared, open dosimetry resource, but its content is Monte Carlo reference physics data rather than patient-level clinical dosimetry. TCIA and the NCI Imaging Data Commons demonstrate that open, licensed sharing of clinical imaging data at scale is technically and legally workable, but no collection there currently pairs radiopharmaceutical dosimetry with clinical outcomes. The gap this idea addresses is the absence of any open resource combining these two proven capabilities for radioligand therapy specifically.","test":"A pilot data-sharing consortium of 5-10 treating centres pooling de-identified post-therapy SPECT/CT or PET/CT dosimetry data and matched clinical outcomes for patients treated with 177Lu-PSMA-617 or 177Lu-DOTATATE into a common, versioned schema, hosted alongside or modelled on TCIA, with success measured by whether a dose-response or dose-toxicity model trained on the pooled data from most centres externally validates against data from a held-out centre not used in training.","maturity":"speculative","actor":"data","cost":"small","horizonYears":5,"route":"/ideas/idea-open-dosimetry-data-commons/"}
{"id":"graves-hyperthyroidism","kind":"indication","name":"Graves' disease and hyperthyroidism","aka":[],"tldr":"An overactive thyroid gland makes too much thyroid hormone, speeding up the whole body. A drink or capsule of radioactive iodine can shrink and quieten the gland from the inside, without surgery.","summary":"Graves' disease, an autoimmune condition in which antibodies stimulate the TSH receptor, is the most common cause of hyperthyroidism, accounting for 60-80% of cases. Oral radioactive iodine-131 has been used to treat it since the 1940s: because the thyroid concentrates iodine, an orally administered dose is taken up almost exclusively by thyroid tissue, which is then irradiated from within by the beta particles, over weeks progressively destroying overactive follicular cells.\n\nWork-up before therapy establishes that the gland is actually iodine-avid: thyroid function tests, and a radioiodine uptake measurement (with I-123 or I-131) or Tc-99m pertechnetate scan, distinguish Graves' disease and toxic nodules (high uptake) from destructive thyroiditis or factitious thyrotoxicosis (low uptake), which will not respond to I-131. Dosing is either a fixed empiric activity or calculated from gland size and the 24-hour uptake to target roughly 2.96-7.4 MBq per gram of thyroid tissue; a serum TSH above about 30 mIU/mL maximises uptake. Antithyroid drugs (methimazole or propylthiouracil) are often used first, or stopped a few days before treatment, to reduce the risk of a transient post-therapy surge in circulating hormone.\n\nThe intended endpoint is a non-hyperthyroid state, and permanent hypothyroidism requiring lifelong levothyroxine is the expected outcome in most patients rather than a complication - it is easier to manage than recurrent thyrotoxicosis. Alternatives are long-term antithyroid drugs or thyroidectomy; the choice among the three is guided by goitre size, ophthalmopathy, pregnancy plans and patient preference rather than by radiopharmaceutical availability. Graves' orbitopathy can worsen after I-131 and this needs to be discussed and sometimes covered with steroids beforehand.","asOf":"2026-09-22","links":[{"label":"SNMMI procedure standard: therapy of thyroid disease with I-131 (sodium iodide), version 3.0","url":"https://jnm.snmjournals.org/content/53/10/1633"},{"label":"ACR-ACNM-ARS-SNMMI-SPR practice parameter for treatment of benign and malignant thyroid disease with I-131 sodium iodide","url":"https://gravitas.acr.org/PPTS/GetDocumentView?docId=29"},{"label":"Graves' disease: review of disease characteristics, burden and treatments (2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13530974/"}],"tags":["thyroid","benign disease","SPECT"],"related":["thyroid-nodule-assessment","tc-99m","i-123","i-131"],"indications":[],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":["radioactive-iodine","thyrotropin-alfa"],"companies":[],"institutions":[],"pathways":[],"terms":["radioiodine-term","half-life"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"thyroid","burden":"Graves' disease affects an estimated 1-1.5% of people worldwide, with an annual incidence of roughly 20-50 new cases per 100,000, and is 5-10 times more common in women; hyperthyroidism from all causes affects about 1.2% of the US population.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Confirmed Graves' disease or toxic nodular goitre, iodine-avid on uptake study","approach":"Oral I-131 sodium iodide, dosed empirically or by calculated activity per gram of thyroid tissue, as one of three first-line options alongside antithyroid drugs and thyroidectomy.","refs":["radioactive-iodine"]},{"setting":"Diagnostic work-up before any hyperthyroidism therapy","approach":"Thyroid function tests plus a radioiodine uptake measurement or Tc-99m pertechnetate scan to confirm iodine avidity and exclude thyroiditis or factitious thyrotoxicosis before committing to I-131.","refs":["radioactive-iodine"]},{"setting":"After I-131 therapy","approach":"Structured follow-up of thyroid function, with levothyroxine started once TSH rises, since iatrogenic hypothyroidism is the expected and accepted outcome of an effective dose.","refs":[]}],"stateOfArt":["The SNMMI/ACR/ACNM/ARS practice parameter and the older SNMMI procedure standard for I-131 sodium iodide therapy set the modern framework: confirm iodine avidity, stop iodine-blocking medications and antithyroid drugs before dosing, verify the prescribed activity in a dose calibrator, and follow written radiation-safety instructions after a therapeutic dose.","Dosing methods still vary between fixed empiric activities (for example roughly 370-555 MBq for Graves' disease per American Thyroid Association ranges) and calculated activities based on gland size and 24-hour uptake; no single method has been shown clearly superior for achieving euthyroidism versus planned ablation to hypothyroidism."],"history":[],"pipeline":[],"openProblems":["No consensus on whether to aim for a euthyroid outcome or deliberately over-treat to hypothyroidism, which trades a higher chance of needing thyroid hormone replacement against a lower chance of needing a second treatment.","Radiation thyroiditis can transiently worsen thyrotoxicosis after treatment, occasionally precipitating thyroid storm in patients with large glands or cardiac disease, who need pre-treatment with antithyroid drugs and beta-blockers.","Graves' orbitopathy may worsen after I-131 in a subset of patients, and the decision to add prophylactic corticosteroids is individualised rather than protocol-driven."],"route":"/indications/graves-hyperthyroidism/"}
{"id":"infection-prosthetic-joint","kind":"indication","name":"Prosthetic joint infection","aka":[],"tldr":"When a replacement hip or knee might be infected, doctors can label a small sample of the patient's own white blood cells with a radioactive tracer and watch, over a day, whether they gather around the implant the way they would around a real infection.","summary":"Distinguishing infection from aseptic loosening around a hip or knee prosthesis matters because the treatments diverge completely: infection needs antibiotics and usually staged revision surgery, while loosening needs a single revision. Radiolabelled white blood cell (WBC) scintigraphy, most often with Tc-99m-HMPAO-labelled autologous leukocytes, is the nuclear medicine reference standard for this question when a three-phase bone scan is positive or equivocal, because inflammatory cells are actively recruited to infected tissue but not to sites of sterile mechanical loosening.\n\nThe EANM procedural guideline specifies three imaging time points - roughly 30-60 minutes, 2-4 hours, and 20-24 hours after reinjection of the labelled cells - because the diagnostic sign is an increase in uptake over time, not simply the presence of uptake; a decrease or stable pattern between the delayed and late images points to a sterile process instead. Reported sensitivity for periprosthetic joint infection is around 86-93% and specificity 94-100% in pooled series, and pairing WBC scintigraphy with a bone marrow scan (Tc-99m sulfur colloid) further increases specificity, since discordant uptake - positive on WBC imaging, negative on marrow imaging - is highly suggestive of infection while concordant uptake in both usually reflects normal marrow expansion rather than infection.\n\nThe 2019 EANM/EBJIS/ESR multidisciplinary consensus places WBC scintigraphy (with or without a bone marrow scan) as the preferred nuclear imaging test after a positive three-phase bone scan, ahead of anti-granulocyte antibody imaging, and notes that antibiotic therapy should not be stopped purely to accommodate the scan, since the evidence that antibiotics blunt its accuracy is weak. FDG PET/CT is an alternative in some centres, but non-standardised uptake criteria around a metal prosthesis and physiological postoperative activity for months after surgery limit its specificity, and the 2024 EANM/SNMMI FDG infection guideline gives detailed protocol points for this specific use.","asOf":"2026-09-22","links":[{"label":"EANM procedural guideline: white blood cell and anti-granulocyte monoclonal antibody scintigraphy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6450843/"},{"label":"Consensus document for the diagnosis of prosthetic joint infections (EANM, EBJIS, ESR, 2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6450843/"},{"label":"EANM/SNMMI guideline/procedure standard for FDG hybrid PET use in infection and inflammation in adults v2.0 (2024/2025)","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2024/EANM%20SNMMI%20Guideline%20FDG%20Infection%20and%20Inflammation_SNMMI%20BOD%20FINAL.pdf"},{"label":"StatPearls: periprosthetic joint infection, incidence data","url":"https://www.ncbi.nlm.nih.gov/books/NBK448131/"}],"tags":["infection","orthopaedics","SPECT"],"related":["fever-of-unknown-origin","tc-99m"],"indications":[],"sections":[],"technologies":["spect-ct","pet-ct","fdg-pet"],"targets":[],"drugs":["technetium-sulfur-colloid","fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"infection","burden":"Prosthetic joint infection complicates roughly 1-2% of primary hip and knee replacements and up to 4% of revisions, out of well over a million hip and knee arthroplasties performed annually in the United States alone; it is now the leading cause of knee revision surgery.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Positive or equivocal three-phase bone scan with suspected prosthetic joint infection","approach":"Tc-99m-HMPAO-labelled autologous white blood cell scintigraphy at three time points (early, delayed, late), read as positive when uptake increases over time; add a bone marrow scan for higher specificity.","refs":[]},{"setting":"Suspected prosthetic joint infection, alternative when WBC labelling is unavailable","approach":"FDG PET/CT, interpreted with awareness that absence of peri-prosthetic uptake has a high negative predictive value but focal peri-prosthetic uptake alone is nonspecific, especially soon after surgery.","refs":[]},{"setting":"Clinical work-up alongside imaging","approach":"Serum CRP/ESR, synovial fluid white cell count and differential, and culture, per the 2019 EANM/EBJIS/ESR consensus criteria that combine clinical, laboratory, imaging and histological findings rather than relying on any single test.","refs":[]}],"stateOfArt":["The EANM procedural guideline for white blood cell and anti-granulocyte scintigraphy (2018) and the 2019 EANM/EBJIS/ESR consensus document define current acquisition, interpretation and diagnostic-pathway standards for periprosthetic joint infection.","The 2024/2025 EANM/SNMMI FDG hybrid PET guideline for infection and inflammation gives updated, indication-specific protocol points for periprosthetic joint infection imaging with FDG PET/CT, including field-of-view and interpretation caveats around metal implants.","SPECT/CT is now recommended whenever planar WBC imaging is positive, since it better localises uptake to bone versus soft tissue and improves overall diagnostic accuracy."],"history":[],"pipeline":[],"openProblems":["WBC labelling is technically demanding, requires an on-site cell-processing lab, takes most of a working day, and is not available in every hospital, which pushes many centres toward less specific FDG PET/CT or serological/synovial-fluid-only pathways.","There is no universally agreed percentage-increase threshold between delayed and late images for calling a scan positive; visual assessment still dominates over quantitative cut-offs.","Recently implanted prostheses (within the first year) still cause false positives on most nuclear imaging modalities because of normal postoperative inflammatory change, narrowing the window in which any of these tests are reliable."],"route":"/indications/infection-prosthetic-joint/"}
{"id":"fever-of-unknown-origin","kind":"indication","name":"Fever of unknown origin","aka":[],"tldr":"When a persistent fever has no obvious cause after the usual tests, a whole-body PET scan using the same sugar tracer as cancer imaging often lights up the hidden infection, inflammation or tumour behind it.","summary":"Fever of unknown origin (FUO) is classically defined as a fever above 38.3C persisting for at least three weeks with no diagnosis despite three outpatient visits or three days as an inpatient; a related entity, inflammation of unknown origin (IUO), is unexplained, persistently raised inflammatory markers without fever. Causes span infection, autoimmune and inflammatory disease, and malignancy, and in a substantial fraction of patients no cause is ever found. Because FDG PET/CT can survey the entire body at once for areas of increased glucose metabolism, it has become the nuclear medicine test of choice for this problem once routine work-up (history, examination, standard blood tests and cultures, chest imaging) has failed to find a cause.\n\nThe joint 2024 SNMMI/Infectious Diseases Society of America/American College of Nuclear Medicine appropriate use criteria rate FDG PET/CT as appropriate for both adult and paediatric FUO, and reserve older techniques - gallium-67 scintigraphy and radiolabelled leukocyte scintigraphy - for situations in which FDG PET/CT is unavailable, with leukocyte scintigraphy specifically for cases where infection is strongly suspected. The 2024/2025 EANM/SNMMI FDG hybrid PET guideline for infection and inflammation gives protocol detail specific to this indication: the scan should ideally be performed before, or as early as possible after, starting antibiotics or oral glucocorticoids, since both can suppress the very uptake being sought, and myocardial suppression preparation should be considered if endocarditis or cardiac sarcoidosis is part of the differential.\n\nDiagnostic yield, rather than sensitivity or specificity in isolation, is the relevant performance measure, because many patients with FUO never get a final causative diagnosis by any test; FDG PET/CT is valued for how often it identifies a focus that can be biopsied or otherwise pinned down, and for its high negative predictive value - a negative scan is associated with a good prognosis and can support a watch-and-wait approach rather than further invasive testing.","asOf":"2026-09-22","links":[{"label":"SNMMI appropriate use criteria factsheet: fever of unknown origin","url":"https://snmmi.org/common/Uploaded%20files/AUC%20Factsheets/Fever_of_Unknown_Origin_AUC_Factsheet.pdf"},{"label":"EANM/SNMMI guideline/procedure standard for FDG hybrid PET use in infection and inflammation in adults v2.0","url":"https://link.springer.com/article/10.1007/s00259-024-06915-3"},{"label":"SNMMI: new appropriate use criteria for FUO (news summary)","url":"https://axisimagingnews.com/radiology-products/imaging-equipment/nuclear-medicine/snmmi-issues-new-guidelines-for-diagnosing-fever-of-unknown-origin"}],"tags":["infection","PET","inflammation"],"related":["infection-prosthetic-joint","ga-67"],"indications":[],"sections":[],"technologies":["fdg-pet","pet-ct"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"infection","burden":"FUO is an uncommon but recurrent diagnostic problem in general and infectious disease practice; systematic reviews put a final diagnosis within reach in roughly half to two-thirds of cases after full modern work-up, with infection, malignancy, and non-infectious inflammatory disease each accounting for a substantial share of identified causes.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Adult or paediatric FUO/IUO without a diagnosis after standard work-up","approach":"Whole-body FDG PET/CT, performed early in the work-up where possible and ideally before or within days of starting corticosteroids or antibiotics.","refs":["fludeoxyglucose-f18"]},{"setting":"FDG PET/CT unavailable, or strong clinical suspicion of infection specifically","approach":"Gallium-67 scintigraphy or radiolabelled leukocyte scintigraphy as second-line nuclear imaging options.","refs":[]}],"stateOfArt":["The 2024 SNMMI/IDSA/ACNM appropriate use criteria formalise FDG PET/CT as the nuclear medicine test of choice for FUO in adults and children, a shift from the historical role of gallium and leukocyte scintigraphy.","The EANM/SNMMI FDG hybrid PET guideline v2.0 (2024/2025) covers fever/inflammation of unknown origin as the first of 19 defined infection and inflammation indications, with specific advice on timing relative to glucocorticoid therapy and on myocardial suppression when a cardiac source is possible.","Cost-effectiveness analyses cited in the EANM consensus document support using FDG PET/CT early in the diagnostic pathway rather than as a last resort, since it can shorten the overall diagnostic process."],"history":[],"pipeline":[],"openProblems":["A meaningful fraction of patients with FUO remain without a final diagnosis even after FDG PET/CT, and the guideline explicitly notes insufficient evidence for its use in patients with normal inflammatory markers.","Interpretation is complicated by physiological brown fat, bowel and myocardial uptake, and by uptake from unrelated incidental findings, all of which require correlation with contrast CT or MRI.","Access and cost mean gallium and leukocyte scintigraphy remain in use in settings without ready PET/CT availability, despite their inferior performance."],"route":"/indications/fever-of-unknown-origin/"}
{"id":"sentinel-node-mapping","kind":"indication","name":"Sentinel lymph node mapping in breast cancer and melanoma","aka":[],"tldr":"Before removing lymph nodes to check whether a breast cancer or melanoma has spread, surgeons inject a small radioactive tracer that flows to the very first node the tumour would reach, so only that node needs to come out to find the answer.","summary":"Sentinel lymph node biopsy replaced routine full axillary or regional lymph node dissection for clinically node-negative breast cancer and melanoma, because the sentinel node - the first node draining the tumour site - accurately predicts the status of the rest of the nodal basin, and removing it alone causes far less lymphoedema and morbidity. Lymphoscintigraphy maps that node before surgery: a radiocolloid (Tc-99m sulfur colloid, albumin colloid, or antimony trisulphide colloid depending on jurisdiction) or the receptor-targeted agent Tc-99m tilmanocept is injected around the tumour or biopsy site, and a gamma camera images its lymphatic drainage over the following one to twenty-four hours.\n\nThe joint EANM/SNMMI practice guidelines for breast cancer and for melanoma specify injection technique (peritumoral, subdermal, periareolar or intradermal depending on the setting), imaging timing (early dynamic imaging immediately after injection to see the draining lymphatic channel, then delayed static images at 1-4 hours and sometimes up to 18-24 hours), and processing including SPECT/CT for anatomically complex drainage such as head and neck melanoma or extra-axillary breast drainage. Tc-99m tilmanocept, approved by the FDA in 2013, targets the mannose-binding CD206 receptor on macrophages within lymph nodes rather than relying on particle size for retention, giving more reliable single-node localisation with less second-echelon node uptake than traditional colloids.\n\nIn the operating theatre, a handheld gamma probe locates the radioactive node(s) intraoperatively, often combined with blue dye or, increasingly, a fluorescent tracer, for direct visual confirmation; the dual technique (radiotracer plus dye) achieves the highest sentinel node identification rates. The procedure has a low radiation burden to both patient and staff and no significant contraindications beyond pregnancy precautions and rare tracer hypersensitivity.","asOf":"2026-09-22","links":[{"label":"EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2013/Final%20Breast%20Sentinel%20Node%20Guideline.pdf"},{"label":"EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2015/2015_EANM_PracticeGL_Lymphoscintigraphy.pdf"},{"label":"SNMMI technologist guideline: lymphoscintigraphy, breast and melanoma","url":"https://tech.snmjournals.org/content/48/4/315"}],"tags":["surgery","SPECT","breast","melanoma"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["tilmanocept-tc99m"],"companies":[],"institutions":[],"pathways":[],"terms":["sentinel-lymph-node-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"surgery","burden":"Sentinel lymph node biopsy is now standard practice for the large majority of clinically node-negative breast cancers and invasive melanomas thicker than 1 mm worldwide, replacing routine axillary or regional lymphadenectomy in these settings.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Clinically node-negative early breast cancer, primary surgery","approach":"Preoperative lymphoscintigraphy with Tc-99m sulfur colloid, albumin colloid or Tc-99m tilmanocept, followed by intraoperative gamma-probe-guided sentinel node biopsy, often combined with blue dye.","refs":[]},{"setting":"Clinically localised invasive melanoma with Breslow thickness above 1 mm","approach":"Lymphoscintigraphy after intradermal peritumoral injection, imaged with dynamic and delayed static views (and SPECT/CT for complex sites such as head and neck), then intraoperative sentinel node biopsy combined with wide local excision.","refs":[]}],"stateOfArt":["The EANM/SNMMI practice guideline for lymphoscintigraphy and sentinel node localisation in breast cancer, and the EANM practice guideline for lymphoscintigraphy and sentinel lymph node biopsy in melanoma (SNMMI-endorsed), define current injection, imaging and reporting standards.","Tc-99m tilmanocept (Lymphoseek) offers CD206 receptor-mediated retention rather than passive particle trapping, giving consistent single-node uptake across breast cancer, melanoma and oral cavity squamous cell carcinoma with a recommended dose of about 18.5-74 MBq depending on same-day or next-day surgery.","SPECT/CT is now recommended whenever planar lymphoscintigraphy is positive in an anatomically ambiguous drainage basin, improving anatomical localisation for the surgeon."],"history":[],"pipeline":[],"openProblems":["Variability in radiocolloid particle size and availability between countries (for example antimony trisulphide colloid in Canada and Australia versus sulfur colloid in the US) means protocols are not fully standardised worldwide.","False-negative sentinel node results still occur, particularly with aberrant or multiple drainage basins, and long-term outcome data are needed as fluorescence-only mapping (without radiotracer) is trialled as a lower-cost alternative in some centres."],"route":"/indications/sentinel-node-mapping/"}
{"id":"renal-obstruction","kind":"indication","name":"Suspected upper urinary tract obstruction","aka":[],"tldr":"When a kidney's drainage tube might be blocked, injecting a tracer that the kidney filters out and watching, with a water pill on board, how fast it washes through shows whether there is a real blockage needing surgery or just a floppy but unobstructed system.","summary":"Hydronephrosis seen on ultrasound or CT does not, by itself, distinguish a genuinely obstructed collecting system that will lose function without intervention from a dilated but freely draining one that needs no treatment. Diuretic renal scintigraphy answers that functional question: a tubular radiopharmaceutical, almost always Tc-99m-mercaptoacetyltriglycine (MAG3), is injected intravenously and its transit through the kidney and drainage into the bladder is followed with a gamma camera, with intravenous furosemide given partway through the study to washout tracer from a non-obstructed system.\n\nThe joint SNMMI/EANM procedure standard specifies a well-hydrated patient, an empty bladder at the start, and either a combined protocol (furosemide at a fixed time, typically 20 minutes, after tracer injection) or a two-stage protocol in which a first 20-30 minute baseline acquisition can exclude obstruction outright if drainage is already brisk, avoiding the need for furosemide at all. MAG3 is preferred over the older glomerular agent Tc-99m-DTPA because its extraction fraction (40-50%) is more than double DTPA's, giving better image quality and more reliable washout curves, especially in kidneys with reduced function. A postvoid image is mandatory whenever obstruction is suspected, since gravity-dependent pooling in an upright, empty-bladder position can otherwise be misread as true retention.\n\nInterpretation combines the differential renal function (the relative contribution of each kidney to overall clearance, calculated from early parenchymal counts) with the washout half-time after furosemide: practical cut-offs commonly used are a half-time under about 10 minutes suggesting no obstruction and over about 20 minutes suggesting true obstruction, with the intermediate range considered equivocal and needing clinical correlation. The test is used both to confirm or exclude obstruction in a symptomatic patient and to establish a functional baseline before deciding on intervention, or before monitoring a conservatively managed kidney over time.","asOf":"2026-09-22","links":[{"label":"SNMMI Procedure Standard/EANM Practice Guideline for diuretic renal scintigraphy in adults with suspected upper urinary tract obstruction 1.0","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6020824/"},{"label":"SNMMI and EANM procedural guidelines for diuresis renography in infants and children","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2018/Pediatric%20Diuresis%20Renal_PSPG.pdf"},{"label":"Diuretic renal scintigraphy protocol considerations (SNMMI Technologist)","url":"https://tech.snmjournals.org/content/50/4/309"}],"tags":["renal","urology","SPECT","dynamic imaging"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":["spect"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"renal","burden":"Diuretic renal scintigraphy is a routine urology and nephrology referral test wherever antenatal or incidental hydronephrosis, ureteropelvic junction obstruction, or post-surgical ureteric stricture is suspected; exact population incidence is not centrally tracked but the test is one of the most frequently performed non-oncological studies in a typical nuclear medicine department.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Adult with suspected upper urinary tract obstruction, symptomatic or with incidental hydronephrosis","approach":"Tc-99m-MAG3 diuretic renal scintigraphy with intravenous furosemide, hydration protocol, and mandatory postvoid imaging, following the SNMMI/EANM procedure standard.","refs":[]},{"setting":"Baseline before planned intervention or nephron-sparing decision","approach":"Diuretic renography to establish differential (split) renal function, used to decide whether a poorly functioning obstructed kidney is worth salvaging or should be considered for nephrectomy.","refs":[]},{"setting":"Paediatric antenatal hydronephrosis or suspected ureteropelvic junction obstruction","approach":"Weight-scaled MAG3 diuresis renography per the SNMMI/EANM paediatric procedural guideline, with furosemide timing (F0, F+20 or F-15) chosen by protocol.","refs":[]}],"stateOfArt":["The SNMMI Procedure Standard/EANM Practice Guideline for diuretic renal scintigraphy in adults with suspected upper urinary tract obstruction (version 1.0, 2018) is the current joint standard, recommending Tc-99m-MAG3 over Tc-99m-DTPA because of its superior extraction fraction.","The companion SNMMI/EANM paediatric guideline for diuresis renography addresses the same question in infants and children, where obstruction most often relates to ureteropelvic junction narrowing detected antenatally.","A postvoid image and, where baseline drainage is already normal, omission of furosemide altogether are both now standard steps to avoid false-positive readings from bladder-related pooling."],"history":[],"pipeline":[],"openProblems":["No universal consensus exists on the exact furosemide timing protocol (F0, F+20, F-15) or on a single washout half-time cut-off; local practice varies and results from different protocols are not always directly comparable.","Impaired renal function, a very large or non-compliant collecting system, and dehydration all reduce test reliability and increase equivocal results, which then need repeat imaging or a therapeutic trial (for example a nephrostomy) to resolve."],"route":"/indications/renal-obstruction/"}
{"id":"gastrointestinal-bleeding","kind":"indication","name":"Gastrointestinal bleeding localisation","aka":[],"tldr":"When bleeding inside the gut is hard to pin down, labelling a patient's own red blood cells with a radioactive tracer and watching where blood leaks into the bowel over several hours can find the source, even if the bleeding comes and goes.","summary":"Gastrointestinal bleeding scintigraphy (GIBS) detects and localises active bleeding into the bowel lumen using the patient's own red blood cells labelled with Tc-99m, exploiting the tracer's long intravascular half-life to allow continuous imaging of the entire gastrointestinal tract for many hours, unlike single-timepoint techniques such as CT angiography. It is used for both overt bleeding (melena, haematochezia) and, less often, occult bleeding, and is particularly valuable because gastrointestinal bleeding is frequently intermittent, so a technique that can watch continuously for extended periods has a real advantage over a snapshot study.\n\nThe SNMMI/ACNM (and previously SNMMI/EANM) procedure standard specifies an administered activity of 555-1,110 MBq of Tc-99m-labelled red blood cells (labelled in vitro, in vivo, or by a modified in vivo technique), dynamic imaging beginning immediately after injection at no more than one frame per 60 seconds, and a minimum of 60 minutes of initial imaging if no bleeding is seen, extendable up to 24 hours by rescanning if there is ongoing clinical suspicion. The diagnostic criteria require all three of: focal activity appearing outside expected blood-pool structures, a change in the intensity of that activity between images, and a pattern of movement consistent with peristalsis through the bowel - meeting only one or two of these criteria is not sufficient to call a positive study.\n\nBecause the test can detect bleeding rates as low as roughly 0.1 mL per minute in clinical use, it is generally more sensitive than catheter angiography (which typically needs faster bleeding, around 0.5-1 mL/min, to show extravasation) and is often used to decide whether, and where, to proceed to angiography and embolisation or, alternatively, direct the endoscopist or surgeon to the likely segment of bowel. It requires no patient preparation, has minimal radiation burden relative to repeated CT, and can be safely performed in haemodynamically unstable patients provided appropriate monitoring is in place.","asOf":"2026-09-22","links":[{"label":"The SNMMI Procedure Standard/EANM Practice Guideline for gastrointestinal bleeding scintigraphy 2.0","url":"https://tech.snmjournals.org/content/42/4/308"},{"label":"The SNMMI Procedure Standard/ACNM Practice Guideline for Gastrointestinal Bleeding Scintigraphy 3.0 (2025)","url":"https://tech.snmjournals.org/content/53/1/14"}],"tags":["gastroenterology","dynamic imaging","emergency"],"related":["tc-99m"],"indications":[],"sections":[],"technologies":["spect"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastroenterology","burden":"Gastrointestinal bleeding is a common reason for hospital admission; lower gastrointestinal bleeding alone accounts for a large share of gastroenterology-related emergency presentations, and GIBS is one of the most frequently requested non-oncological nuclear medicine studies performed on an urgent basis.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Suspected active overt gastrointestinal bleeding, source unclear on endoscopy or unstable for endoscopy","approach":"Tc-99m-labelled red blood cell scintigraphy, imaged dynamically for a minimum of 60 minutes and extendable to 24 hours, read as positive only when focal extravascular activity changes in intensity and moves in a bowel pattern.","refs":[]},{"setting":"Positive scintigraphy, further localisation or treatment needed","approach":"Catheter angiography with embolisation, or surgery, targeted to the segment identified on scintigraphy.","refs":[]}],"stateOfArt":["The SNMMI Procedure Standard/ACNM Practice Guideline for Gastrointestinal Bleeding Scintigraphy 3.0 (2025) is the current version, building on the 2014 SNMMI/EANM standard, and formalises the three-part positivity criteria and updated paediatric weight-based dosing.","Tc-99m-RBC scintigraphy remains more sensitive for intermittent, low-rate bleeding than CT angiography or catheter angiography, which need a higher active bleeding rate to show extravasation at the single moment of image acquisition."],"history":[],"pipeline":[],"openProblems":["Serial intermittent static imaging is explicitly discouraged in favour of continuous dynamic acquisition, but adherence to this varies across centres with older equipment or workflow constraints.","The scan localises bleeding to a general bowel region rather than a precise anatomical point, so it complements rather than replaces endoscopy or angiography for definitive treatment planning.","In vivo versus in vitro red blood cell labelling technique affects labelling efficiency and image quality; the highest-efficiency in vitro kit-based labelling is not universally available."],"route":"/indications/gastrointestinal-bleeding/"}
{"id":"pulmonary-embolism-vq","kind":"indication","name":"Pulmonary embolism: ventilation/perfusion imaging","aka":[],"tldr":"To check whether a blood clot has lodged in the lung's blood vessels, a scan compares which parts of the lung get air (ventilation) with which parts get blood flow (perfusion); a clot shows up as an area that is ventilated but not perfused.","summary":"Ventilation/perfusion (V/Q) scintigraphy diagnoses or excludes acute pulmonary embolism by comparing two maps of the lung obtained in the same sitting: a perfusion map, made by injecting Tc-99m-labelled macroaggregated albumin (MAA) particles that lodge in pulmonary capillaries in proportion to blood flow, and a ventilation map, made with an inhaled agent such as Technegas or krypton-81m gas. A pulmonary embolus blocks a branch of the pulmonary artery, so the perfusion map shows a wedge-shaped defect in that lung segment while the corresponding ventilation map remains normal - a mismatch that is the scintigraphic hallmark of embolism, as opposed to a matched defect where both are reduced together, typical of parenchymal lung disease rather than embolism.\n\nThe 2019 EANM guideline for V/Q SPECT strongly recommends tomographic (SPECT) rather than planar imaging wherever available, since SPECT has higher sensitivity and specificity, and defines a positive study as a mismatch of at least one segment or two subsegments conforming to pulmonary vascular anatomy; a normal perfusion study, respecting the anatomical boundaries of the lungs, excludes pulmonary embolism outright regardless of any other finding. Combining V/Q SPECT with a low-dose CT further improves specificity, particularly in patients with coexisting chronic obstructive pulmonary disease, heart failure or pneumonia, all of which can otherwise complicate interpretation.\n\nV/Q scanning has a substantially lower radiation dose than CT pulmonary angiography, no iodinated contrast requirement, and virtually no absolute contraindications, which makes it the preferred first-line test in pregnancy, in patients with renal impairment or contrast allergy, and in younger patients where lifetime radiation exposure is a bigger consideration. ACR appropriateness criteria and SNMMI/EANM/ASH/ACCP/ACEP appropriate use criteria both support V/Q scanning or CT pulmonary angiography as appropriate first-line tests for suspected pulmonary embolism with intermediate or high pre-test probability, with the choice between them driven by patient factors (pregnancy, renal function, chest radiograph findings, local availability) rather than one modality being universally superior.","asOf":"2026-09-22","links":[{"label":"EANM guideline for ventilation/perfusion SPECT for diagnosis of pulmonary embolism and beyond (2019)","url":"https://pubmed.ncbi.nlm.nih.gov/31410539/"},{"label":"SNMMI appropriate use criteria for ventilation/perfusion (V/Q) imaging in pulmonary embolism","url":"https://snmmi.org/Web/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate-Use-Criteria-for-Ventilation-Perfusion--V-Q--Imaging-in-Pulmonary-Embolism.aspx"},{"label":"CDC: data and statistics on venous thromboembolism","url":"https://www.cdc.gov/blood-clots/data-research/facts-stats/index.html"}],"tags":["pulmonary","SPECT","emergency","cardiopulmonary"],"related":["technegas","tc-99m-maa","kr-81m","cyclopharm","tc-99m"],"indications":[],"sections":[],"technologies":["spect","spect-ct"],"targets":[],"drugs":["technegas","tc-99m-maa"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"pulmonary","burden":"Pulmonary embolism has an estimated annual incidence in the United States of roughly 60-115 cases per 100,000 people, is part of a broader venous thromboembolism burden affecting up to 900,000 Americans a year, and is the third most common cause of cardiovascular death after coronary artery disease and stroke.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Suspected acute pulmonary embolism, intermediate or high pre-test probability, especially pregnancy or contraindication to iodinated contrast","approach":"Ventilation/perfusion SPECT (or SPECT/CT), interpreted per EANM criteria: mismatch of at least one segment or two subsegments confirms PE, normal perfusion excludes it.","refs":["technegas","tc-99m-maa","kr-81m"]},{"setting":"Suspected acute pulmonary embolism, general population without a specific reason to avoid contrast","approach":"CT pulmonary angiography or V/Q scanning, either considered appropriate first-line by ACR and SNMMI/multi-society appropriate use criteria, chosen by local availability and patient factors.","refs":[]}],"stateOfArt":["The 2019 EANM guideline for ventilation/perfusion SPECT for diagnosis of pulmonary embolism and beyond is the current European reference standard, recommending Technegas or krypton gas over Tc-99m-DTPA aerosol in patients with COPD and SPECT over planar imaging throughout.","The SNMMI-led multi-society (with EANM, ASH, STS, ACCP, ACEP) appropriate use criteria for V/Q imaging in pulmonary embolism, most recently updated 2020, give scenario-by-scenario appropriateness ratings endorsed by both the American Society of Hematology and American College of Emergency Physicians.","V/Q SPECT/CT combines the mismatch read with low-dose anatomical correlation, improving specificity in patients with coexisting COPD, heart failure or pneumonia that would otherwise confound interpretation."],"history":[],"pipeline":[],"openProblems":["Probabilistic (PIOPED-style) interpretation categories are now considered flawed by EANM and have been replaced by a simpler binary/nondiagnostic scheme, but older planar-based probabilistic reporting persists in some centres.","A 'nondiagnostic' or intermediate-probability result still occurs in a meaningful minority of studies and usually requires a second test (CT pulmonary angiography or clinical follow-up) to resolve.","Real-world uptake of SPECT over planar V/Q imaging, and of Technegas over older ventilation agents, remains uneven internationally, driven by equipment and radiopharmaceutical availability rather than by guideline preference alone."],"route":"/indications/pulmonary-embolism-vq/"}
{"id":"bone-pain-palliation","kind":"indication","name":"Bone pain palliation from osteoblastic metastases","aka":[],"tldr":"For cancer that has spread widely to bone and causes pain everywhere at once, a bone-seeking radioactive injection travels to every affected spot in the skeleton and delivers pain-relieving radiation from the inside, sparing a trip to radiotherapy for each site.","summary":"Widespread osteoblastic (bone-forming) metastases, most often from prostate or breast cancer, can cause diffuse skeletal pain that is impractical to treat site-by-site with external beam radiotherapy. Systemically administered beta-emitting bone-seeking radiopharmaceuticals - strontium-89 chloride, samarium-153 lexidronam (153Sm-EDTMP) and, historically, phosphorus-32 sodium phosphate - concentrate at sites of increased osteoblastic turnover in proportion to bone remodelling activity, verified beforehand by a positive radionuclide bone scan, and deliver local beta radiation to relieve pain over one to a few weeks. The alpha-emitting radium-223 dichloride is a related but distinct case: as a calcium mimetic it also concentrates in osteoblastic bone lesions, but it is FDA- and EMA-approved specifically for castration-resistant prostate cancer with symptomatic bone metastases and no visceral disease, and, unlike the older beta emitters, it prolongs overall survival, not just pain.\n\nThe SNMMI/EANM procedure standard for these agents recommends 89Sr-chloride at roughly 148 MBq (or 1.5-2.2 MBq/kg), 153Sm-EDTMP at 37 MBq/kg, and 223Ra-dichloride at 55 kBq/kg every four weeks for six cycles; all three are given as a slow intravenous injection with attention to avoiding extravasation. Only 223Ra-dichloride has shown a survival benefit (from the ALSYMPCA trial); 89Sr and 153Sm are recommended solely for pain palliation and are not associated with any demonstrated survival advantage, and neither should be given to patients with a life expectancy under about four weeks because of a lag of days to weeks before pain relief.\n\nSelection is straightforward but firm: patients need painful lesions that are osteoblastic (not lytic) and bone-scan-avid, adequate baseline blood counts because myelosuppression is the dose-limiting toxicity of the beta emitters in particular, and no impending spinal cord compression or pathological fracture risk, which need surgery or external beam radiotherapy instead. Concomitant bisphosphonates are not contraindicated. Weekly complete blood counts are recommended for eight weeks after treatment, or until recovery from the nadir, given the risk of cytopenias.","asOf":"2026-09-22","links":[{"label":"SNMMI Procedure Standard/EANM Practice Guideline for radionuclide therapy of painful bone metastases","url":"https://tech.snmjournals.org/content/51/3/176"},{"label":"EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5978928/"},{"label":"FDA medical review: radium Ra 223 dichloride (Xofigo), NDA 203971","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203971Orig1s000MedR.pdf"}],"tags":["palliative care","bone metastases","alpha therapy","beta emitter"],"related":["ra-223","sm-153","sr-89","p-32"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":["radium-223","samarium-153-lexidronam","phosphorus-32"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca"],"people":[],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":[],"group":"palliative care","burden":"Bone metastases occur in a large majority of men who die of prostate cancer and a majority of women with metastatic breast cancer, and painful skeletal metastases are one of the most common causes of cancer-related pain requiring systemic, rather than site-specific, treatment.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Diffuse painful osteoblastic bone metastases from any solid tumour, confirmed osteoblastic on bone scan","approach":"Strontium-89 chloride or samarium-153-EDTMP for pain palliation; no proven survival benefit, and inappropriate if life expectancy is under about four weeks.","refs":["alsympca"]},{"setting":"Castration-resistant prostate cancer with symptomatic bone metastases and no visceral disease","approach":"Radium-223 dichloride, six cycles at 55 kBq/kg every four weeks, chosen over the older beta emitters because it also improves overall survival and delays symptomatic skeletal events.","refs":["alsympca"]},{"setting":"Before any bone-seeking radiopharmaceutical","approach":"Confirm osteoblastic, bone-scan-avid lesions and adequate blood counts; exclude impending cord compression or pathological fracture, which need surgery or external beam radiotherapy instead.","refs":[]}],"stateOfArt":["The SNMMI Procedure Standard/EANM Practice Guideline for radionuclide therapy of painful bone metastases (updated version discussed in 2023 SNMMI technologist literature) sets current dosing, patient selection and monitoring practice for 89Sr, 153Sm-EDTMP and 223Ra-dichloride, and notes that 32P sodium phosphate is no longer available for this use in the United States.","Radium-223's approval, based on the phase 3 ALSYMPCA trial (median overall survival 14.9 vs 11.3 months for placebo), remains the only agent in this class with a demonstrated survival benefit; its US label is currently restricted to castration-resistant prostate cancer with symptomatic bone metastases and no visceral disease.","About 60% of patients receiving radium-223 experience meaningful pain reduction, with an estimated 3-4 month survival extension reported across analyses of the pivotal trial population."],"history":[],"pipeline":[],"openProblems":["Strontium-89 and samarium-153 remain palliative only, with no survival benefit shown in any trial, and their future use may narrow further as radium-223 and lutetium-177-based radioligand therapies increasingly address the same castration-resistant prostate cancer population earlier in the disease course.","Myelosuppression from the beta emitters can delay or preclude subsequent chemotherapy, an important sequencing consideration in patients who may still be candidates for later systemic therapy.","Selecting between radium-223, PSMA-targeted lutetium-177 radioligand therapy and standard therapies in castration-resistant prostate cancer with bone-only disease is an active area of clinical judgement rather than settled guideline, particularly regarding sequencing and combination."],"route":"/indications/bone-pain-palliation/"}
{"id":"epilepsy-localisation","kind":"indication","name":"Presurgical localisation of drug-resistant focal epilepsy","aka":[],"tldr":"For seizures that medication cannot control, a brain PET scan taken between seizures can spot the small area of brain that is misfiring, by showing it using less sugar than the tissue around it, helping surgeons plan an operation to remove it.","summary":"Around a third of people with epilepsy do not achieve seizure control with antiseizure medication and are candidates for evaluation toward resective surgery, which requires precisely identifying the epileptogenic zone - the area of brain that must be removed or disconnected to stop seizures. Interictal FDG PET (performed between seizures, ideally at least 24-48 hours after the last one) is one of the core presurgical tests alongside video-EEG monitoring and structural MRI, because the epileptogenic zone and the neural networks that sustain it typically show reduced glucose metabolism (hypometabolism) interictally, an effect that is usually more pronounced and spatially extensive than any corresponding reduction in blood flow.\n\nThe joint 2024 SNMMI/EANM guideline for brain FDG PET imaging (version 2.0) and the EANM practice guideline for appropriate PET and SPECT use in epilepsy specify continuous EEG monitoring starting before FDG injection and continuing for at least 20 minutes afterwards, precisely to confirm the scan captures a genuinely interictal state rather than a post-ictal one, which would show a different and misleading metabolic pattern. Performance is markedly better in temporal lobe epilepsy, where meta-analyses report roughly 79-95% sensitivity and specificity for lateralising the epileptogenic side, than in extratemporal epilepsy, where the epileptogenic zone is correctly identified in only about 38-67% of cases; PET's higher spatial resolution gives it an edge over interictal perfusion SPECT (84% versus 66% sensitivity in one meta-analysis for temporal lobe epilepsy).\n\nCoregistration of PET with MRI, either on a combined PET/MRI system or by image fusion, is emphasised because it lets clinicians directly match a metabolic abnormality with any structural lesion (or reveal one that was missed on MRI alone), and because more limited extent of hypometabolism on PET carries prognostic value both for postsurgical seizure freedom and for postoperative cognitive outcome. Ictal SPECT, using an agent injected as close as possible to seizure onset (ideally within 20 seconds, via a pre-placed line and automatic injector during video-EEG monitoring), is a complementary technique used particularly when PET and MRI are discordant or non-lateralising, showing increased rather than decreased blood flow at the seizure focus during the seizure itself.","asOf":"2026-09-22","links":[{"label":"SNMMI Procedure Standard/EANM Practice Guideline for Brain FDG PET Imaging, version 2.0 (2024)","url":"https://jnm.snmjournals.org/content/early/2024/10/17/jnumed.124.268754"},{"label":"EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11139752/"},{"label":"Review: drug-resistant epilepsy definition, pathophysiology and management (burden figures)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12593530/"}],"tags":["neurology","PET","epilepsy","presurgical"],"related":[],"indications":[],"sections":[],"technologies":["fdg-pet","pet-mri","spect"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"neurology","burden":"Epilepsy affects an estimated 50-65 million people worldwide, and roughly 30-40% of those with epilepsy do not achieve seizure freedom with medication and are potential candidates for surgical work-up, of whom presurgical PET and video-EEG evaluation are core components in comprehensive epilepsy centres.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Presurgical evaluation of focal drug-resistant epilepsy in adults and children","approach":"Interictal FDG PET, with continuous EEG monitoring from before injection to at least 20 minutes after, coregistered with MRI to localise the epileptogenic zone alongside video-EEG telemetry.","refs":[]},{"setting":"PET and MRI non-lateralising or discordant with EEG","approach":"Ictal SPECT, with tracer injected as close as possible to seizure onset during video-EEG monitoring, to show focal hyperperfusion at seizure onset.","refs":[]}],"stateOfArt":["The SNMMI Procedure Standard/EANM Practice Guideline for Brain FDG PET Imaging, version 2.0 (2024), and the EANM practice guidelines for appropriate use of PET and SPECT in epilepsy (2024) are the current joint references for patient preparation, EEG timing, acquisition and interpretation.","Reported sensitivity for lateralising temporal lobe epilepsy with interictal FDG PET is around 79-95% in pooled analyses, clearly outperforming interictal perfusion SPECT (about 66-84%), while extratemporal epilepsy localisation succeeds in only about 38-67% of cases.","PET-MRI coregistration and quantitative asymmetry-index analysis are now standard adjuncts to visual reading, and the extent of hypometabolism carries prognostic value for both seizure and cognitive outcome after surgery."],"history":[],"pipeline":[],"openProblems":["Extratemporal epilepsy remains substantially harder to localise than temporal lobe epilepsy with any single imaging modality, and often needs invasive stereo-EEG in addition to PET and MRI.","Bilateral or diffusely symmetric hypometabolism can be missed on visual reading alone, a recognised pitfall the guideline specifically flags.","Timing relative to the last seizure is critical but not always practically achievable in busy epilepsy monitoring units, and inadvertent post-ictal imaging can produce misleading hypometabolic or hypermetabolic patterns."],"route":"/indications/epilepsy-localisation/"}
{"id":"thyroid-nodule-assessment","kind":"indication","name":"Functional assessment of thyroid nodules","aka":[],"tldr":"When a lump is found in the thyroid, a scan showing whether it takes up iodine-like tracer more or less than the rest of the gland tells doctors whether it is a low-risk overactive nodule that rarely needs a biopsy, or a quiet 'cold' nodule that does.","summary":"Thyroid nodules are extremely common, and the central triage question once one is found and the patient's TSH is checked is not usually 'is this cancer' outright, but 'does this nodule need a biopsy'. Thyroid scintigraphy, using either iodine-123 or Tc-99m-pertechnetate, answers a narrower but very useful part of that question: whether the nodule is functioning autonomously (a 'hot' nodule, taking up more tracer than surrounding tissue) or non-functioning ('cold', taking up less). Guidelines converge on scintigraphy being indicated specifically when serum TSH is low or low-normal, because a hyperfunctioning nodule found in that setting is very unlikely to be malignant - reported negative predictive value for malignancy in hot nodules is around 96-99% - and can often avoid fine-needle aspiration biopsy altogether, going instead toward treatment of the underlying autonomy (radioactive iodine or surgery) if symptomatic.\n\nACR appropriateness criteria correspondingly rate thyroid scintigraphy (I-123 uptake, or I-131/Tc-99m-pertechnetate) as usually not appropriate for an initial, euthyroid, palpable nodule where ultrasound is the right first test, but usually appropriate once thyrotoxicosis is present, reflecting that the scan's value lies in explaining biochemical hyperthyroidism found alongside a nodule, or a multinodular goitre, rather than in routinely characterising every palpable lump. The 2019 EANM/SNMMI radioiodine uptake and scintigraphy guideline notes that different national guidelines disagree on exactly which TSH threshold or nodule size should trigger a scan, reflecting genuine practice variation between US, German and pan-European recommendations.\n\nBecause the great majority of thyroid cancers are 'cold' on scintigraphy, but the great majority of cold nodules are in turn benign (up to 80-90%), a cold result is not itself diagnostic and simply routes the nodule onward to ultrasound risk stratification (such as ACR TI-RADS) and, if indicated by size and sonographic features, fine-needle aspiration cytology - the scan narrows the population needing biopsy rather than replacing biopsy. In iodine-avid nodules with indeterminate cytology, adjunct molecular or metabolic imaging (Tc-99m-sestamibi or FDG PET) has been explored to further refine malignancy risk, but is not part of routine first-line assessment.","asOf":"2026-09-22","links":[{"label":"EANM practice guideline/SNMMI procedure standard for radioiodine uptake and scintigraphy (2019)","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2019/EANM%20SNMMI%20Radio%20Iodine%20Uptake%20(RAIU)%20and%20Scintigraphy.pdf"},{"label":"ACR Appropriateness Criteria: thyroid disease","url":"https://acsearch.acr.org/docs/3102386/narrative/"},{"label":"Investigating thyroid nodules (review, ACR TI-RADS and functional imaging)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8671014/"}],"tags":["thyroid","SPECT","triage"],"related":["graves-hyperthyroidism","tc-99m","i-123","i-131"],"indications":[],"sections":[],"technologies":["spect"],"targets":[],"drugs":["radioactive-iodine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"thyroid","burden":"Thyroid nodules are found on ultrasound in a large proportion of the adult population (commonly cited at up to half of adults by sensitive imaging), the great majority are benign, and only a small minority prove malignant on biopsy, making appropriate triage - rather than universal biopsy - the central clinical challenge.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Palpable or incidentally found thyroid nodule, euthyroid, initial work-up","approach":"Ultrasound first; thyroid scintigraphy is not indicated at this stage per ACR appropriateness criteria.","refs":[]},{"setting":"Thyroid nodule with low or low-normal serum TSH (biochemical thyrotoxicosis)","approach":"Tc-99m-pertechnetate or I-123 thyroid scintigraphy to determine whether the nodule is autonomously functioning ('hot', very low malignancy risk, usually no biopsy needed) or non-functioning ('cold', routed to ultrasound risk stratification and possible biopsy).","refs":[]},{"setting":"Multinodular goitre","approach":"Scintigraphy to identify hypofunctioning ('cold') areas within the goitre that specifically warrant fine-needle aspiration, since function cannot be inferred from ultrasound risk features alone.","refs":[]}],"stateOfArt":["The EANM practice guideline/SNMMI procedure standard for radioiodine uptake and thyroid scintigraphy (2019) sets the current joint acquisition and interpretation standard, and explicitly tabulates how ATA, German, and AACE/AME/ETA guidelines differ on scanning thresholds.","ACR appropriateness criteria rate ultrasound as usually appropriate for essentially every thyroid nodule scenario, and reserve thyroid scintigraphy for scenarios with confirmed or suspected thyrotoxicosis, where it is usually appropriate.","A hyperfunctioning ('hot') nodule carries a well-established 96-99% negative predictive value for malignancy, a figure robust enough that current risk-stratification systems such as ACR TI-RADS are understood to apply primarily to nodules not already known to be autonomously functioning."],"history":[],"pipeline":[],"openProblems":["National guidelines disagree on the TSH level and nodule size that should trigger scintigraphy, so practice varies meaningfully between the US, Germany and other European guidance, without a single internationally harmonised threshold.","A 'cold' scan result has low specificity for malignancy (most cold nodules are benign), so scintigraphy narrows rather than replaces the ultrasound-and-biopsy pathway, and cannot be used alone to reassure a patient a nodule is benign.","Adjunct techniques (Tc-99m-sestamibi washout imaging, FDG PET) for indeterminate-cytology cold nodules are used in some centres to help decide on diagnostic surgery, but are not yet standard first-line practice."],"route":"/indications/thyroid-nodule-assessment/"}
{"id":"f-18","kind":"isotope","name":"Fluorine-18","aka":["18F"],"tldr":"A short-lived radioactive form of fluorine, made fresh each morning at a local facility, that is attached to a sugar or other small molecule and used for a PET scan.","summary":"Fluorine-18 is the workhorse radionuclide of clinical PET. Its 109.8-minute half-life is long enough for a regional cyclotron to make a batch, run it through automated radiochemistry and quality control, and ship unit doses to nearby hospitals, but short enough that the whole chain has to be scheduled tightly around the day's scan list; roughly a third of the activity is lost every hour.\n\nAlmost all clinical 18F is made by firing protons at water enriched in oxygen-18, driving the 18O(p,n)18F reaction to give no-carrier-added [18F]fluoride in solution, which is then used in automated synthesis modules to build tracers such as FDG, PSMA and amyloid agents. It decays 96.7% by positron emission and 3.3% by electron capture, giving the 511 keV annihilation photon pair that PET detects.\n\nBecause the half-life supports regional distribution, F-18 tracers do not depend on a single generator or reactor the way technetium-99m or gallium-68 historically have; supply risk sits instead with cyclotron and radiopharmacy network capacity (PETNET, Cardinal Health, GE HealthCare, Jubilant, SOFIE and others) rather than with a single upstream bottleneck.","status":"established","asOf":"2026-09-22","links":[{"label":"FDA label: Fludeoxyglucose F 18 Injection (initial approval 2005)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021870lbl.pdf"},{"label":"IAEA TRS 468: cyclotron production of 18F","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/trs468_web.pdf"},{"label":"PMC: PET imaging with 18F-based radiopharmaceuticals","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3478111/"}],"tags":["positron emitter","cyclotron"],"related":["fludeoxyglucose-f18","pylarify","psma-1007-f18","fluoroestradiol-f18","flotufolastat","fluciclovine-f18"],"indications":[],"sections":[],"technologies":["pet","pet-ct","cyclotron-isotope-production","pet-tracer-manufacturing","fdg-pet","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"18F","element":"Fluorine","massNumber":18,"halfLife":"109.8 minutes","emissions":["β+ 96.7% (max 0.634 MeV)","electron capture 3.3%","annihilation γ 511 keV"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 18O(p,n)18F on water enriched in oxygen-18 (no-carrier-added fluoride); 20Ne(d,α)18F on neon gas is an older electrophilic-fluorine route, now largely abandoned.","supply":"adequate","supplyNote":"Regional cyclotron networks (PETNET Solutions/Siemens, Cardinal Health, GE HealthCare, SOFIE, Jubilant Radiopharma) distribute unit doses across metropolitan areas; the 110-minute half-life is long enough for same-morning delivery, so supply is not dependent on a single site the way generator-based isotopes are.","chelators":[],"pairedWith":[],"since":1976,"route":"/isotopes/f-18/"}
{"id":"ga-68","kind":"isotope","name":"Gallium-68","aka":["68Ga"],"tldr":"A radioactive metal with a one-hour lifetime that is eluted from a shielded generator or made on a cyclotron and attached to a molecule that finds tumours, giving a PET scan the same day.","summary":"Gallium-68 decays with a 67.7-minute half-life, mostly by positron emission, and is the diagnostic half of two of the most important theranostic pairs in oncology: 68Ga-DOTATATE/DOTATOC paired with 177Lu-DOTATATE for neuroendocrine tumours, and 68Ga-PSMA-11 paired with 177Lu-PSMA-617 or 225Ac-PSMA for prostate cancer.\n\nIt is traditionally produced by eluting a 68Ge/68Ga generator, where the 270.8-day parent 68Ge is fixed to a column and decays continuously; the daughter is washed off with dilute acid on demand. Commercial GMP generators (Eckert & Ziegler, IRE, ITG) top out at 1.85-3.7 GBq per elution, and lead times for new units have historically run to 18 months, which constrained the launch of PSMA PET in the late 2010s. A cyclotron route, direct 68Zn(p,n)68Ga irradiation of a liquid or solid target, produces roughly a curie per run against a generator's 40-50 mCi and has been promoted by the IAEA since a 2019 technical document and a 2020 coordinated research project as the way to relieve that bottleneck.\n\nBy the mid-2020s the practical supply picture had eased: Eckert & Ziegler expanded generator manufacturing capacity after a 2017 germanium shortage, and cyclotron-produced 68Ga (including for PSMA-11) is now used at large centres alongside the F-18-labelled PSMA alternatives (Pylarify, PSMA-1007, flotufolastat) that took share once generator lead times became a launch constraint.","status":"established","asOf":"2026-09-22","links":[{"label":"IAEA: cyclotron-based gallium-68 for cancer detection (2024)","url":"https://www.iaea.org/newscenter/news/alternatives-for-accessing-lifesaving-diagnostic-radioisotopes-cyclotron-based-gallium-68-for-cancer-detection"},{"label":"PMC: Current status of the production and supply of gallium-68","url":"https://pubmed.ncbi.nlm.nih.gov/32196363/"},{"label":"IAEA TE-2127: good management practices of cyclotron-based Ga-68 production","url":"https://www-pub.iaea.org/MTCD/publications/PDF/TE-2127web.pdf"},{"label":"Applied Radiation Oncology: nuclear medicine prepares for greater 68Ga demand (2021)","url":"https://www.appliedradiationoncology.com/articles/nuclear-medicine-prepares-for-greater-68ga-demand"}],"tags":["positron emitter","generator","theranostic pair"],"related":["ga68-dotatate","ga68-psma-11","illuccix","locametz","ge-68"],"indications":[],"sections":[],"technologies":["sstr-pet","psma-pet","pet","radionuclide-generators-kits","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":["eckert-ziegler","ire","isotopia","telix","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"68Ga","element":"Gallium","massNumber":68,"halfLife":"67.7 minutes","emissions":["β+ 89% (max 1.90 MeV)","electron capture 11%","annihilation γ 511 keV"],"emissionClass":"positron","use":"imaging","production":"68Ge/68Ga generator (elution with dilute HCl) or cyclotron 68Zn(p,n)68Ga on enriched zinc-68 liquid or solid target.","supply":"adequate","supplyNote":"Generator lead times of up to 18 months and a 2017 germanium shortage constrained supply during the PSMA PET launch; expanded generator manufacturing (Eckert & Ziegler GalliaPharm/GeGant) and IAEA-promoted cyclotron production (roughly 1 Ci per run versus 40-50 mCi per generator elution) have since relieved the bottleneck.","chelators":["DOTA","NOTA","HBED-CC"],"pairedWith":["lu-177","ac-225"],"since":2016,"route":"/isotopes/ga-68/"}
{"id":"tc-99m","kind":"isotope","name":"Technetium-99m","aka":["99mTc","Tc-99m"],"tldr":"The single most widely used medical radioisotope: a metastable metal with a six-hour lifetime, milked on demand from a bedside generator (a 'moly cow') and attached to a cold kit to image bone, heart, kidneys or lymph nodes.","summary":"Technetium-99m decays with a 6.0067-hour half-life, almost entirely by isomeric transition, emitting a 140.5 keV gamma ray that sits close to the energy of diagnostic X-ray equipment and is close to ideal for gamma-camera and SPECT imaging. It underpins on the order of tens of millions of scans a year worldwide (bone scans, myocardial perfusion, sentinel lymph node mapping, renal and hepatobiliary studies), each prepared on site by adding the eluted pertechnetate to a lyophilised cold kit.\n\nIt is the daughter of molybdenum-99 (65.94-hour half-life), which is shipped to hospital and radiopharmacy radiopharmacies worldwide as a 99Mo/99mTc generator; the longer-lived parent decays continuously and the daughter is eluted, typically once or twice a day, for use within hours before it decays away. This generator relationship is what makes just-in-time global distribution of a six-hour isotope possible at all.\n\nBecause supply of 99mTc is entirely downstream of 99Mo production, its reliability tracks the well-documented fragility of that upstream reactor supply chain (see mo-99): unplanned reactor outages, most recently the October 2024 shutdown of the High Flux Reactor in the Netherlands, have repeatedly caused short-notice shortages of Tc-99m-based scans.","status":"established","asOf":"2026-09-22","links":[{"label":"NNDC/LNHB: Tc-99m decay data tables","url":"http://www.lnhb.fr/nuclides/Tc-99m_tables.pdf"},{"label":"OECD/NEA: current trends in the supply and utilisation of medical radioisotopes (2025)","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"}],"tags":["gamma emitter","generator","most widely used"],"related":["technetium-sulfur-colloid","tilmanocept-tc99m","mo-99"],"indications":[],"sections":[],"technologies":["spect","spect-ct","radionuclide-generators-kits","research-reactor-isotope-production","nuclear-medicine-hardware"],"targets":[],"drugs":[],"companies":["curium","ge-healthcare","lantheus","cardinal-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"99mTc","element":"Technetium","massNumber":99,"halfLife":"6.0067 hours","emissions":["γ 140.5 keV (89%)","internal conversion electrons (~11% of decays)"],"emissionClass":"gamma","use":"imaging","production":"Eluted from a 99Mo/99mTc generator (the '99Mo/99mTc generator' or 'moly cow'); 99Mo is made by fission of enriched uranium targets in a research reactor or by neutron activation of enriched molybdenum-98.","supply":"tight","supplyNote":"Supply is set entirely by upstream 99Mo production; ageing research reactors and periodic unplanned outages (for example the HFR shutdown of October 2024) have caused recurrent short-notice Tc-99m shortages despite no direct constraint on technetium itself.","chelators":[],"pairedWith":[],"since":1964,"route":"/isotopes/tc-99m/"}
{"id":"i-123","kind":"isotope","name":"Iodine-123","aka":["123I"],"tldr":"A radioactive form of iodine that decays quickly and gives off gamma rays, used to take a picture of the thyroid or, attached to a nerve-tracing molecule, of tumours of the adrenal gland and nervous system, before deciding whether a therapeutic dose of iodine-131 makes sense.","summary":"Iodine-123 has a 13.2-hour half-life and decays by electron capture with a dominant 159 keV gamma emission well suited to gamma-camera and SPECT imaging. Its main clinical roles are thyroid uptake and scintigraphy, and as the diagnostic imaging partner to iobenguane (MIBG): 123I-MIBG scintigraphy stages neuroblastoma and phaeochromocytoma/paraganglioma before or alongside treatment with the therapeutic 131I-MIBG.\n\nIt is cyclotron-produced, never reactor-produced, most commonly via 124Xe(p,2n)123Cs, which decays through 123Xe to 123I, or via the (p,pn) channel on the same enriched xenon-124 target; a 123Te(p,n)123I route on enriched tellurium is also used. Both routes need a medium-energy cyclotron (20-30 MeV) and an expensive enriched target, which keeps 123I costlier and less universally available than reactor- or generator-based isotopes, and its 13-hour half-life limits how far it can be shipped before it has decayed away.\n\nBecause iodine's biochemistry is essentially identical across its isotopes, 123I plays the same diagnostic-before-therapeutic role for iodine and MIBG imaging that 68Ga and 18F play for peptide and small-molecule theranostics.","status":"established","asOf":"2026-09-22","links":[{"label":"PMC: perspective on production and quality control of iodine-123","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12121839/"},{"label":"Radiopaedia: iodine-123","url":"https://radiopaedia.org/articles/iodine-123?lang=us"}],"tags":["gamma emitter","cyclotron","thyroid"],"related":["iobenguane-i-131","i131-mibg","i-124"],"indications":["neuroblastoma","pheochromocytoma-paraganglioma","thyroid"],"sections":[],"technologies":["spect","mibg-theranostics","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"123I","element":"Iodine","massNumber":123,"halfLife":"13.2 hours","emissions":["γ 159 keV (83%)","electron capture"],"emissionClass":"gamma","use":"imaging","production":"Cyclotron: 124Xe(p,2n)123Cs → 123Xe → 123I or 124Xe(p,pn)123Xe → 123I on enriched xenon-124 gas targets; alternatively 123Te(p,n)123I on enriched tellurium-123.","supply":"tight","supplyNote":"Requires a medium-energy (20-30 MeV) cyclotron and an expensive enriched xenon-124 or tellurium-123 target, so production is concentrated at a small number of sites worldwide; the 13.2-hour half-life limits shipping range, which has caused regional shortages.","chelators":[],"pairedWith":["i-131"],"since":1970,"route":"/isotopes/i-123/"}
{"id":"i-124","kind":"isotope","name":"Iodine-124","aka":["124I"],"tldr":"A long-lived, PET-visible form of radioactive iodine used to map how a thyroid cancer takes up iodine over several days, so the dose of the treatment isotope, iodine-131, can be planned before it is given.","summary":"Iodine-124 decays with a 4.18-day half-life by a mix of electron capture and positron emission (positron abundance about 23%), giving it PET-imageable annihilation photons over a timescale of days rather than the minutes-to-hours typical of most PET isotopes. Because it shares iodine's biochemistry with the therapeutic isotope 131I, serial 124I PET/CT scans, typically at roughly 24 and 96-120 hours after a tracer dose, let physicists build a time-activity curve for each lesion and project the absorbed dose per unit of a subsequent 131I therapy activity, rather than relying on a fixed empiric dose.\n\nIts decay scheme is complex: only about 23% of decays produce a positron (mean energy 819 keV, giving relatively poor spatial resolution), while high-energy prompt gammas (603 keV and others) contaminate the coincidence signal, so scanners need isotope-specific calibration rather than the F-18 calibration used by default; published work has found this calibration factor can differ from F-18 by roughly ten percent.\n\nIt is cyclotron-produced by proton bombardment of enriched tellurium-124, 124Te(p,n)124I, chosen for high radionuclidic purity at proton energies below about 14 MeV, though yields from this reaction are comparatively low, and by the older 124Te(d,2n)124I route.","status":"emerging","asOf":"2026-09-22","links":[{"label":"PMC: I-124 imaging and dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5283715/"},{"label":"MDPI: radiochemistry, production and immunoPET imaging of iodine-124","url":"https://www.mdpi.com/1420-3049/26/2/414"}],"tags":["positron emitter","long-lived PET","pre-therapy dosimetry"],"related":["radioactive-iodine","i-123"],"indications":["thyroid"],"sections":[],"technologies":["pet","radioligand-dosimetry","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"124I","element":"Iodine","massNumber":124,"halfLife":"4.18 days","emissions":["β+ 23% (max ~2.14 MeV)","electron capture ~77%","γ 603 keV (61%)","annihilation γ 511 keV (46%)"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 124Te(p,n)124I on enriched tellurium-124 (proton energies below ~14 MeV for high radionuclidic purity); older 124Te(d,2n)124I route also used.","supply":"constrained","supplyNote":"Low reaction yield and the need for an expensive enriched tellurium-124 target mean 124I is produced at only a limited number of cyclotron centres, mostly for dosimetry research and thyroid-cancer pre-therapy planning rather than routine clinical stock.","chelators":[],"pairedWith":["i-131"],"since":1994,"route":"/isotopes/i-124/"}
{"id":"in-111","kind":"isotope","name":"Indium-111","aka":["111In"],"tldr":"A radioactive metal used, attached to octreotide, as the original scan for neuroendocrine tumours (Octreoscan) before gallium-68 PET took over, and still used to label white blood cells for infection imaging.","summary":"Indium-111 decays by electron capture to stable cadmium-111 with a 2.805-day half-life, emitting gamma photons suited to gamma-camera and SPECT imaging. For two decades it was the standard somatostatin-receptor imaging agent as 111In-pentetreotide (Octreoscan), used to select neuroendocrine tumour patients before peptide receptor radionuclide therapy, first with 90Y-labelled and later with 177Lu-labelled somatostatin analogues; SPECT-based Octreoscan has since been largely replaced by 68Ga- or 64Cu-DOTATATE PET, which has better resolution and quantification, but 111In-pentetreotide remains on label and in use where PET access is limited.\n\nIt is produced on a cyclotron by proton bombardment of an enriched cadmium target, either 112Cd(p,2n)111In or 111Cd(p,n)111In, the latter giving higher radionuclidic purity. Its 2.8-day half-life is long enough to ship internationally and to track slower-clearing tracers such as labelled leukocytes and antibody fragments, which is why it is also used for infection and inflammation imaging (111In-labelled white cells) and in some antibody biodistribution and dosimetry studies.","status":"established","asOf":"2026-09-22","links":[{"label":"FDA/DailyMed label: OctreoScan (indium In 111 pentetreotide)","url":"https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=93d8f3b2-1216-41dc-a63d-0e812b33891d"},{"label":"Wikipedia: indium-111 (production routes)","url":"https://en.wikipedia.org/wiki/Indium-111"}],"tags":["gamma emitter","legacy somatostatin imaging"],"related":["ga68-dotatate","lutathera"],"indications":["neuroendocrine"],"sections":[],"technologies":["spect","spect-ct","sstr-pet","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"111In","element":"Indium","massNumber":111,"halfLife":"2.805 days","emissions":["γ 171 keV (90%)","γ 245 keV (94%)","electron capture"],"emissionClass":"gamma","use":"imaging","production":"Cyclotron: 111Cd(p,n)111In (higher purity) or 112Cd(p,2n)111In on enriched cadmium targets.","supply":"adequate","supplyNote":"Cyclotron-produced at a moderate number of sites; demand has fallen substantially since 68Ga/64Cu-DOTATATE PET replaced 111In-pentetreotide SPECT as the preferred somatostatin-receptor imaging test.","chelators":["DTPA"],"pairedWith":["y-90","lu-177"],"since":1994,"route":"/isotopes/in-111/"}
{"id":"cu-64","kind":"isotope","name":"Copper-64","aka":["64Cu"],"tldr":"A radioactive metal that lasts about half a day, long enough to image slower-moving molecules such as antibodies, and chemically identical to copper-67, the isotope used to treat with the same tracer.","summary":"Copper-64 has an unusually long half-life for a positron emitter, 12.7 hours, and a three-way decay: 17.5-19% positron emission, roughly 40-44% electron capture, and about 38-39% beta-minus decay, so the same nuclide gives PET signal and a small therapeutic beta dose. Its half-life is long enough to image both fast-clearing peptides and slower-clearing antibodies and nanoparticles, and it forms a same-element theranostic pair with copper-67, which shares the identical chelation chemistry so a diagnostic 64Cu scan predicts the biodistribution of a 67Cu therapy exactly.\n\nIt is produced almost exclusively on medical cyclotrons via 64Ni(p,n)64Cu on an enriched nickel-64 target electroplated onto a metal backing, a well-established, high-specific-activity route; a bombardment of a few hours on a 40 mg target can yield roughly 18.5 GBq. Reactor routes (64Zn(n,p)64Cu, 63Cu(n,γ)64Cu) exist but give lower specific activity and are used less often clinically.\n\nBecause the 64Ni target is expensive and the reaction requires a dedicated cyclotron run, 64Cu is made at a limited number of centres and supplied regionally rather than being universally available the way 18F is; the sstr2-targeted 64Cu-DOTATATE (Detectnet) is the main approved clinical use in the United States.","status":"approved","asOf":"2026-09-22","links":[{"label":"IAEA: copper-64 radiopharmaceuticals, production, quality control","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1961_web.pdf"},{"label":"PMC: recent advances in 64Cu/67Cu-based radiopharmaceuticals (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10288943/"}],"tags":["positron emitter","theranostic pair","same-element pair"],"related":["ga68-dotatate"],"indications":[],"sections":[],"technologies":["sstr-pet","pet","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"64Cu","element":"Copper","massNumber":64,"halfLife":"12.7 hours","emissions":["β+ 17.5% (max 0.653 MeV)","electron capture ~44%","β− 38.5% (max 0.579 MeV)","annihilation γ 511 keV"],"emissionClass":"mixed","use":"imaging","production":"Cyclotron: 64Ni(p,n)64Cu on enriched nickel-64 target (dominant route); reactor 64Zn(n,p)64Cu or 63Cu(n,γ)64Cu give lower specific activity.","supply":"emerging","supplyNote":"Limited to cyclotron centres with enriched 64Ni targets; regional supply rather than universal, but expanding alongside interest in the 64Cu/67Cu theranostic pair.","chelators":["DOTA","SARTATE/SAR-bisPSMA (sarcophagine cages)"],"pairedWith":["cu-67"],"since":2020,"route":"/isotopes/cu-64/"}
{"id":"zr-89","kind":"isotope","name":"Zirconium-89","aka":["89Zr"],"tldr":"A radioactive metal that lasts about three days, long enough to attach to a whole antibody and follow it around the body for several days on a PET scan, which is why it underpins 'immuno-PET'.","summary":"Zirconium-89 decays with a 78.4-hour (3.3-day) half-life, mostly by electron capture (about 77%) and partly by positron emission (about 23%), to metastable yttrium-89, which promptly emits a 909 keV gamma. That three-day half-life is the reason 89Zr is the default radiometal for immuno-PET: intact monoclonal antibodies take two to four days to reach optimal tumour-to-background ratios in vivo, far longer than any conventional PET isotope survives, but well matched to zirconium-89's decay.\n\nIt is made almost entirely by cyclotron bombardment of a solid yttrium-89 target, 89Y(p,n)89Zr; because yttrium-89 is 100% naturally abundant the target needs no isotopic enrichment, which keeps production comparatively simple and inexpensive, though proton energy has to be kept below about 13 MeV to avoid the long-lived 88Zr impurity. After irradiation, 89Zr is purified on a hydroxamate resin and conjugated to antibodies through chelators such as desferrioxamine (DFO) or newer macrocyclic cages designed to resist the free-zirconium bone uptake that DFO-based constructs can show over several days.\n\nIn the Nuclide graph, 89Zr's main current oncology use is CAIX PET with 89Zr-girentuximab in renal cell carcinoma, which forms an emerging diagnostic-therapeutic pair with 177Lu- or 225Ac-labelled girentuximab.","status":"emerging","asOf":"2026-09-22","links":[{"label":"Springer: clinical nuclear medicine applications of zirconium-89 immuno-PET","url":"https://link.springer.com/article/10.1186/s41181-025-00418-8"},{"label":"EJNMMI Radiopharmacy & Chemistry: good practices for 89Zr production","url":"https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-024-00258-y"}],"tags":["positron emitter","immuno-PET","long-lived PET"],"related":["girentuximab-zr89"],"indications":["rcc"],"sections":[],"technologies":["immuno-pet","caix-pet","cyclotron-isotope-production","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"89Zr","element":"Zirconium","massNumber":89,"halfLife":"78.4 hours (3.3 days)","emissions":["electron capture ~77%","β+ ~23% (mean 396 keV)","γ 909 keV (from 89mY, 99%)"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 89Y(p,n)89Zr on a solid yttrium-89 target (proton energy kept below ~13 MeV to avoid 88Zr impurity); 89Y(d,2n)89Zr with deuterons is an alternative.","supply":"adequate","supplyNote":"Yttrium-89 is 100% naturally abundant and needs no enrichment, and purification chemistry is well established, so 89Zr is considered one of the more scalable non-conventional PET radiometals; several commercial suppliers now provide it.","chelators":["DFO (desferrioxamine)","DFO*","macropa/other next-generation cages"],"pairedWith":["lu-177","ac-225"],"since":2010,"route":"/isotopes/zr-89/"}
{"id":"c-11","kind":"isotope","name":"Carbon-11","aka":["11C"],"tldr":"A radioactive form of ordinary carbon that lasts only about 20 minutes, so it has to be made and used in the same building; it can label real body molecules like choline without changing their chemistry.","summary":"Carbon-11 decays by positron emission (about 99.8% of the time) with a physical half-life of only 20.4 minutes, the shortest half-life of any radionuclide in routine clinical use. Because carbon is the backbone atom of biological molecules, replacing a stable carbon-12 with carbon-11 gives a radiotracer that is chemically indistinguishable from its natural counterpart, unlike fluorine- or metal-based tracers that are typically synthetic analogues.\n\nThe half-life is so short that C-11 cannot be shipped: it must be produced, synthesised into a tracer, quality-tested and injected within the same facility, on the same clock, which is why C-11 programmes exist only at large academic or hospital sites with an on-site cyclotron and radiochemistry suite immediately adjacent to the PET scanner. Almost all clinical C-11 comes from the 14N(p,α)11C reaction, bombarding nitrogen gas with protons to give [11C]carbon dioxide or, with added hydrogen, [11C]methane, which is then converted to the reactive methylating agent [11C]methyl iodide or [11C]methyl triflate to label a precursor molecule such as choline or methionine.\n\nCholine C-11 was approved by the FDA in September 2012 for PET imaging of suspected recurrent prostate cancer with non-informative conventional imaging, and remains one of the few full-NDA radiopharmaceuticals that can only be produced and used on site.","status":"established","asOf":"2026-09-22","links":[{"label":"FDA label: Choline C 11 Injection (NDA 203155, approved 12 Sep 2012)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61f00cb4-ea53-4ba6-a890-78586095d2f6"},{"label":"PMC: synthesis, isolation and purification of [11C]-choline","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5013686/"}],"tags":["positron emitter","ultra-short-lived","on-site only"],"related":["choline-c11"],"indications":["prostate"],"sections":[],"technologies":["pet","cyclotron-isotope-production","choline-metabolism-in-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"11C","element":"Carbon","massNumber":11,"halfLife":"20.4 minutes","emissions":["β+ ~99.8% (max 0.96 MeV)","electron capture ~0.2%"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 14N(p,α)11C on nitrogen gas target (with trace oxygen for [11C]CO2 or trace hydrogen for [11C]CH4), converted to [11C]methyl iodide or [11C]methyl triflate for labelling.","supply":"research-only","supplyNote":"The 20.4-minute half-life rules out shipping entirely; every dose is made and used at the same site, so availability is limited to institutions with an on-site cyclotron and radiochemistry, mostly academic centres.","chelators":[],"pairedWith":[],"since":1973,"route":"/isotopes/c-11/"}
{"id":"n-13","kind":"isotope","name":"Nitrogen-13","aka":["13N"],"tldr":"A radioactive gas-forming isotope with a ten-minute lifetime, turned into ammonia and injected to map blood flow to the heart muscle on a PET scan.","summary":"Nitrogen-13 decays by pure positron emission with a 9.97-minute half-life. Its main clinical use is as ammonia N-13 injection, an FDA-approved PET myocardial perfusion agent (initial US approval 2007) used at rest and under pharmacological stress to evaluate suspected or existing coronary artery disease; it clears the blood with a biological half-life of under three minutes and is trapped in viable myocardium as glutamine.\n\nIt is made on a cyclotron via the 16O(p,α)13N reaction, typically by irradiating a dilute ethanol-in-water target, with the proton beam degraded to avoid co-producing oxygen-15 by the competing 16O(p,pn)15O channel. Because the ten-minute half-life is even shorter than fluorine-18's, N-13 ammonia must be made on site or very close to the scanner, which historically limited it to centres with an in-house cyclotron; compact superconducting mini-cyclotrons introduced in the 2010s and 2020s have made single-site N-13 ammonia production more practical for community cardiac PET programmes.\n\nAlongside 82Rb and 15O-water, 13N-ammonia is one of only a small number of PET perfusion tracers, and one of only two (with 82Rb) that carry FDA approval for that indication in the United States.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Ammonia N 13 Injection (initial approval 2007)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022119s001lbl.pdf"},{"label":"PMC: reliable production of large quantities of [13N]ammonia","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10254488/"}],"tags":["positron emitter","ultra-short-lived","cardiac perfusion"],"related":[],"indications":[],"sections":[],"technologies":["pet","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"13N","element":"Nitrogen","massNumber":13,"halfLife":"9.97 minutes","emissions":["β+ 100% (max 1.19 MeV)","annihilation γ 511 keV"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 16O(p,α)13N, typically on a dilute ethanol-in-water liquid target, with proton energy degraded to suppress the competing 16O(p,pn)15O reaction.","supply":"research-only","supplyNote":"The 9.97-minute half-life requires production essentially at the scanner; compact on-site mini-cyclotrons have widened access beyond large academic centres but supply remains site-by-site rather than distributed.","chelators":[],"pairedWith":[],"since":1970,"route":"/isotopes/n-13/"}
{"id":"o-15","kind":"isotope","name":"Oxygen-15","aka":["15O"],"tldr":"A radioactive form of oxygen with a two-minute lifetime, made into water and injected to measure blood flow to the brain or heart; used almost exclusively in research because it decays too fast for routine hospital use in the US.","summary":"Oxygen-15 has the shortest half-life of any radionuclide used in PET, 122 seconds (about two minutes), and decays by pure positron emission. Labelled as [15O]water, it diffuses freely across cell membranes and its uptake is not confounded by metabolism, which makes it the physics gold standard for quantifying regional cerebral or myocardial blood flow; the very short half-life also allows repeat rest and stress or activation scans in the same session only 10-15 minutes apart, with a very low cumulative radiation dose.\n\nProduction requires an on-site cyclotron: nitrogen gas is bombarded with deuterons, 14N(d,n)15O, to give [15O]oxygen gas, which is then reacted over a heated palladium catalyst to form [15O]water vapour that is dissolved into saline for injection. Because a scan can only happen within a couple of minutes' walk of the cyclotron, [15O]water PET is confined to a small number of specialised academic centres worldwide.\n\n[15O]water PET myocardial and cerebral blood flow imaging is clinically approved and reimbursed in a number of European countries but, as of the mid-2020s, has not received FDA approval for routine US clinical use, so its US role remains research and investigational protocols rather than everyday practice.","status":"emerging","asOf":"2026-09-22","links":[{"label":"PMC: EANM procedural guidelines for PET/CT quantitative myocardial perfusion (O-15/N-13/Rb-82/F-18-flurpiridaz comparison table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7603916/"},{"label":"PMC: frugal and translatable [15O]O2 production for human research","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11083888/"}],"tags":["positron emitter","shortest-lived PET isotope","cerebral blood flow"],"related":[],"indications":[],"sections":[],"technologies":["pet","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"15O","element":"Oxygen","massNumber":15,"halfLife":"122 seconds (about 2 minutes)","emissions":["β+ 100% (mean energy ~735 keV)","annihilation γ 511 keV"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 14N(d,n)15O on nitrogen gas target, converted to [15O]water over a heated palladium catalyst; 15N(p,n)15O and 16O(p,pn)15O are alternative routes.","supply":"research-only","supplyNote":"The 122-second half-life confines use to sites with an on-site cyclotron directly adjacent to the scanner; not FDA-approved for routine US clinical use as of the mid-2020s, though it is approved and reimbursed in parts of Europe.","chelators":[],"pairedWith":[],"since":1970,"route":"/isotopes/o-15/"}
{"id":"rb-82","kind":"isotope","name":"Rubidium-82","aka":["82Rb"],"tldr":"A radioactive potassium look-alike that lasts only about 75 seconds, delivered straight from a bedside generator into a vein, used to check blood flow to the heart without needing a cyclotron on site.","summary":"Rubidium-82 decays with a physical half-life of about 76 seconds, essentially entirely by positron emission, and behaves biologically as a potassium analogue that is extracted by viable myocardium in proportion to blood flow. Because the half-life is far too short to survive transport from a cyclotron, it is instead produced continuously by a strontium-82/rubidium-82 generator: the roughly 25-day parent 82Sr is bound to a column and the daughter is eluted with saline directly into an automated infusion system at the point of injection.\n\nAlongside 13N-ammonia it is one of only two PET myocardial perfusion tracers with FDA approval in the United States (marketed as CardioGen-82, and successor generator products), and its extremely short half-life allows a full rest-and-pharmacologic-stress study to be completed in around 20-30 minutes with very high patient throughput, since a decayed dose clears within minutes and cannot be reused. Because trace amounts of the parent 82Sr and the contaminant 85Sr can break through the column, US regulations (10 CFR 35.204) cap the breakthrough at 0.02 microcurie of 82Sr and 0.2 microcurie of 85Sr per millicurie of 82Rb eluted, and generators require daily quality control.\n\nUnlike an on-site cyclotron tracer, 82Rb needs no local radiochemistry infrastructure at all beyond the generator and infusion pump, which is why it has spread to community cardiac PET programmes that could never support 13N-ammonia or 15O-water.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: CardioGen-82 (rubidium Rb 82 generator)","url":"https://www.bracco.com/us-en-2020-11-24-spc-cardiogen-82"},{"label":"FDA: CardioGen-82 information","url":"https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/cardiogen-82-information"},{"label":"PMC: rubidium-82 generator yield and efficiency for PET perfusion imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7599151/"}],"tags":["positron emitter","generator","cardiac perfusion","ultra-short-lived"],"related":[],"indications":[],"sections":[],"technologies":["pet","radionuclide-generators-kits"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"82Rb","element":"Rubidium","massNumber":82,"halfLife":"76 seconds","emissions":["β+ ~95% (max 3.35 MeV)","annihilation γ 511 keV"],"emissionClass":"positron","use":"imaging","production":"Sr-82/Rb-82 generator: 82Sr (half-life ~25 days, itself accelerator-produced) is loaded on a column and 82Rb is eluted with saline on demand.","supply":"adequate","supplyNote":"Generator-based; supply depends on accelerator production of the 82Sr parent, which is made at a small number of specialised facilities, but the roughly 25-day parent half-life lets a single generator serve a clinic for about four weeks between changes.","chelators":[],"pairedWith":[],"since":1989,"route":"/isotopes/rb-82/"}
{"id":"ga-67","kind":"isotope","name":"Gallium-67","aka":["67Ga"],"tldr":"An older radioactive gallium tracer, given as a citrate injection, that lights up infections and some tumours over a scan taken a few days later; mostly replaced now by FDG PET but still used where PET is unavailable.","summary":"Gallium-67 decays by electron capture with a 3.26-day (78.3-hour) half-life, emitting a set of gamma rays (93, 185 and 300 keV) suited to planar gamma-camera and SPECT imaging. Complexed with citrate as 67Ga-citrate, it accumulates in inflammatory and infectious foci and in a range of tumours, historically including lymphoma, hepatoma and bronchogenic carcinoma, and was for decades the standard whole-body tumour and infection imaging agent before FDG PET became widely available.\n\nIt is produced on a cyclotron by proton bombardment of enriched zinc-68, the 68Zn(p,2n)67Ga reaction, and its multi-day half-life means imaging is typically performed 24-72 hours after injection to let background activity clear, at the cost of a comparatively high radiation burden and lower image resolution than modern PET agents.\n\nClinical use of 67Ga-citrate has declined sharply since the 2000s as FDG-PET/CT displaced it for lymphoma and most solid-tumour indications, and it now survives mainly as a second-line option for infection and inflammation imaging where PET access, FDG production or reimbursement pose barriers.","status":"historic","asOf":"2026-09-22","links":[{"label":"DailyMed/FDA label: Gallium Citrate Ga 67","url":"https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5f670c12-cca5-4d73-8a88-241f753d1bc7"},{"label":"Nordion: gallium-67 fact sheet","url":"https://www.nordion.com/wp-content/uploads/2014/10/MI_Gallium-67_Canada.pdf"}],"tags":["gamma emitter","legacy tumour and infection imaging"],"related":[],"indications":["neuroendocrine"],"sections":[],"technologies":["spect","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"67Ga","element":"Gallium","massNumber":67,"halfLife":"3.26 days (78.3 hours)","emissions":["γ 93 keV (38%)","γ 185 keV (21%)","γ 300 keV (17%)"],"emissionClass":"gamma","use":"imaging","production":"Cyclotron: 68Zn(p,2n)67Ga on enriched zinc-68 target.","supply":"adequate","supplyNote":"Clinical demand has fallen substantially since FDG-PET/CT took over most oncology and infection-imaging indications previously served by gallium scans; remaining production is cyclotron-based and dispensed daily by commercial radiopharmacies.","chelators":[],"pairedWith":[],"since":1969,"route":"/isotopes/ga-67/"}
{"id":"tl-201","kind":"isotope","name":"Thallium-201","aka":["201Tl"],"tldr":"A radioactive potassium look-alike with a three-day lifetime, injected to see how well blood reaches, and heart muscle survives in, different parts of the heart on a SPECT scan.","summary":"Thallium-201 decays by electron capture to stable mercury-201 with a 73-hour (about 3-day) physical half-life, and is handled biologically as a potassium analogue, taken up by viable myocardium in proportion to regional blood flow and cell membrane integrity. Imaging exploits the mercury X-rays emitted at 69-83 keV (about 88 per 100 decays) rather than its weaker 135 and 167 keV gamma rays, using a low-energy collimator.\n\nIt is produced on a cyclotron by proton bombardment of enriched thallium-203, via 203Tl(p,3n)201Pb, and the resulting lead-201 (half-life about 9.4 hours) is left to decay for roughly a day before a second chemical separation yields carrier-free thallium-201.\n\nBecause its relatively long physical and biological half-lives allow flexible same-day or next-day rest/redistribution imaging without a dedicated on-site cyclotron, thallium-201 was the dominant myocardial perfusion SPECT agent for decades; it has since been substantially displaced by technetium-99m-based perfusion agents (which give a lower radiation dose and better image quality) but remains in use, particularly for myocardial viability assessment, where thallium's redistribution behaviour is diagnostically useful.","status":"established","asOf":"2026-09-22","links":[{"label":"Radiopaedia: thallium-201 scintigraphy","url":"https://radiopaedia.org/articles/thallium-201-scintigraphy"},{"label":"Health Canada product monograph: Thallous Chloride Tl 201 Injection","url":"https://pdf.hres.ca/dpd_pm/00050840.PDF"}],"tags":["gamma emitter","cardiac perfusion","myocardial viability"],"related":[],"indications":[],"sections":[],"technologies":["spect","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"201Tl","element":"Thallium","massNumber":201,"halfLife":"73 hours (3.04 days)","emissions":["Hg X-rays 69-83 keV (~88%)","γ 135 keV (~3%)","γ 167 keV (~10%)"],"emissionClass":"gamma","use":"imaging","production":"Cyclotron: 203Tl(p,3n)201Pb on enriched thallium-203, followed by decay of 201Pb (half-life ~9.4 hours) to 201Tl and a second chemical separation.","supply":"adequate","supplyNote":"Cyclotron-produced at a limited number of high-energy facilities; clinical demand has declined relative to Tc-99m myocardial perfusion agents but remains in routine use for viability studies.","chelators":[],"pairedWith":[],"since":1975,"route":"/isotopes/tl-201/"}
{"id":"sc-44","kind":"isotope","name":"Scandium-44","aka":["44Sc"],"tldr":"An experimental radioactive metal, lasting about four hours, being developed as a PET-imageable stand-in for lutetium-177 or other therapy metals so a treatment dose can be planned in advance.","summary":"Scandium-44 decays with a 3.97-hour half-life and an unusually high positron branching ratio of about 94%, giving PET image quality that compares favourably with gallium-68 while lasting roughly three times as long, long enough for regional distribution from a centralised production site rather than only local cyclotron use. Its chemistry closely resembles that of lutetium-177 and other trivalent lanthanide-like therapy metals, so DOTA-chelated scandium-44 tracers have been explored as a pre-therapy dosimetry match for 177Lu-labelled radioligands such as PSMA-617, an alternative to using 68Ga for the diagnostic scan when a metal-matched surrogate is preferred.\n\nIt is produced on a medical cyclotron via 44Ca(p,n)44Sc on an enriched calcium-44 target (natural abundance only about 2%, so enrichment adds cost), or via a 44Ti/44Sc generator in which the long-lived (60.4-year) parent titanium-44 supplies scandium-44 on an ongoing basis without a cyclotron, analogous to a 68Ge/68Ga generator.\n\nScandium-44 is also discussed as the diagnostic half of a prospective 44Sc/47Sc theranostic pair, since 44Sc and the beta-emitting therapy isotope scandium-47 are chemically identical, but as of the mid-2020s this pairing remains in early clinical and preclinical research rather than routine practice, and 47Sc production has not yet reached clinical scale.","status":"preclinical","asOf":"2026-09-22","links":[{"label":"PMC: production of scandium radionuclides for theranostic applications","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8149571/"},{"label":"PMC: current state of 44Ti/44Sc radionuclide generator systems","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10375575/"}],"tags":["positron emitter","generator","experimental theranostic pair"],"related":[],"indications":[],"sections":[],"technologies":["pet","cyclotron-isotope-production","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"44Sc","element":"Scandium","massNumber":44,"halfLife":"3.97 hours","emissions":["β+ 94.3% (mean 632 keV)","γ 1157 keV (99.9%)"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 44Ca(p,n)44Sc on enriched calcium-44 target; alternatively a 44Ti/44Sc generator (44Ti half-life ~60 years).","supply":"research-only","supplyNote":"Produced at a small number of research cyclotron and generator sites; enriched calcium-44 targets and 44Ti generator stock are both limited, and no scandium radiopharmaceutical has reached routine clinical supply as of the mid-2020s.","chelators":["DOTA"],"pairedWith":[],"since":2013,"route":"/isotopes/sc-44/"}
{"id":"y-86","kind":"isotope","name":"Yttrium-86","aka":["86Y"],"tldr":"A PET-visible radioactive stand-in for the treatment isotope yttrium-90, used to see in advance, on a scan, exactly where a yttrium-90 therapy dose would go and how much radiation each organ would receive.","summary":"Yttrium-90, used for radioembolisation (TARE/SIRT) and older radioimmunotherapy agents, is a pure beta emitter with no directly imageable gamma or positron emission, which makes patient-specific pre-therapy dosimetry difficult. Yttrium-86 solves that problem: it is chemically identical to yttrium-90, so an 86Y-labelled version of the same antibody, peptide or microsphere construct has an identical biodistribution, and its 14.7-hour half-life with about 33% positron emission allows PET imaging over two to three days, long enough to build a full time-activity curve and calculate the organ and tumour doses a subsequent 90Y therapy would deliver.\n\nIt is produced on a cyclotron via 86Sr(p,n)86Y on an enriched strontium-86 target (typically SrCO3 or SrO), the preferred route because it gives the highest radionuclidic purity; the main radionuclidic impurity, 87mY, is normally kept below a few percent when highly enriched target material is used. Bombardments of a few hours at modest beam currents (2-6 microamps) are typical.\n\nThe approach was first used clinically at Forschungszentrum Jülich for pre-therapy dosimetry ahead of 90Y-citrate treatment of bone metastases, and has since been applied to 86Y-DOTA-peptide imaging ahead of 90Y-labelled somatostatin analogue therapy; it remains a research and specialist-dosimetry tool rather than a routinely stocked clinical isotope, since both the cyclotron target and the imaging protocol are non-standard.","status":"preclinical","asOf":"2026-09-22","links":[{"label":"PMC: 86Y-based PET radiopharmaceuticals, radiochemistry and applications","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3184346/"},{"label":"DOE Isotope Program (NIDC): yttrium-86 availability","url":"https://www.isotopes.gov/node/215"}],"tags":["positron emitter","dosimetry surrogate","theranostic pair"],"related":[],"indications":[],"sections":[],"technologies":["pet","radioligand-dosimetry","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"86Y","element":"Yttrium","massNumber":86,"halfLife":"14.7 hours","emissions":["β+ ~33% (max 3.15 MeV)","electron capture ~67%","multiple γ (443-1921 keV)"],"emissionClass":"positron","use":"imaging","production":"Cyclotron: 86Sr(p,n)86Y on enriched strontium-86 target (SrCO3 or SrO), typically 2-6 microamp beam current for under 4 hours.","supply":"research-only","supplyNote":"Made at a small number of research cyclotrons (including the US DOE Isotope Program's Brookhaven Linac Isotope Producer, available on an as-needed basis) with enriched 86Sr targets; used for dosimetry research rather than stocked as a routine clinical isotope.","chelators":["DOTA"],"pairedWith":["y-90"],"since":1993,"route":"/isotopes/y-86/"}
{"id":"mo-99","kind":"isotope","name":"Molybdenum-99","aka":["99Mo","Mo-99"],"tldr":"The parent isotope shipped worldwide to make technetium-99m, the gamma-ray tracer used in the majority of nuclear medicine scans. It is made in a handful of ageing research reactors, and when one breaks down, scans get delayed or cancelled.","summary":"Molybdenum-99 decays with a 65.94-hour (about 2.75-day) half-life to technetium-99m, and its whole purpose in the supply chain is to act as a transportable parent: its longer half-life lets bulk 99Mo be irradiated, processed and shipped internationally to radiopharmacies, which then load it into 99Mo/99mTc generators and elute the six-hour daughter locally, on demand, for the roughly tens of millions of Tc-99m scans performed worldwide each year.\n\nHistorically some 90-95% of global 99Mo came from just five ageing research reactors, three in Europe (BR2 in Belgium, HFR in the Netherlands, and the now-closed OSIRIS in France), one in Canada (the now-closed NRU) and one in South Africa (SAFARI-1); by the OECD/NEA's 2025 accounting the surviving fleet, including BR2 and HFR, remains dominated by reactors that were not designed for continuous isotope production and were commissioned in the mid-20th century, so unplanned outages are a recurring risk: an October 2024 structural fault forced an unplanned shutdown of the HFR, which combined with scheduled maintenance elsewhere to worsen shortages of both 99Mo and 99mTc that winter.\n\nThe other defining event of the last fifteen years has been the conversion from highly enriched uranium (HEU, historically 45-98% 235U) fission targets to low-enriched uranium (LEU, under 20% 235U) for non-proliferation reasons: Curium's Netherlands processing facility completed conversion in January 2018, and IRE (Belgium) completed its conversion in March 2023, after which the OECD/NEA estimated that more than 90% of global bulk 99Mo production capacity came from non-HEU sources. LEU targets are less efficient and generate more waste per curie produced, and the industry's underlying economic problem, according to repeated OECD/NEA studies, is that irradiation and processing prices have historically been too low to fund the reactor and processing capacity replacement the ageing fleet needs; the 2010 NEA economic study estimated irradiation-service prices would need to rise by up to roughly a factor of nine to be sustainable. New non-fission routes are diversifying supply: NorthStar's RadioGenix System, which produces 99Mo by neutron activation of enriched or natural molybdenum targets rather than uranium fission, reached commercial scale in the 2020s (though NorthStar separately announced in 2023 a temporary halt to one production line), and Australia's ANSTO and South Africa's NTP Radioisotopes remain major LEU-fission suppliers outside the historic European/Canadian core.","status":"established","asOf":"2026-09-22","links":[{"label":"OECD/NEA: current trends in the supply and utilisation of medical radioisotopes (2025)","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"},{"label":"OECD/NEA: the security of supply of medical radioisotopes, 2023-2027 demand and capacity projections","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2023-10/nea_ndc_r_2023_1.pdf"},{"label":"OECD/NEA: an economic study of the molybdenum-99 supply chain","url":"https://www.oecd-nea.org/med-radio/reports/MO-99.pdf"}],"tags":["beta emitter","generator parent","reactor supply chain","ageing infrastructure"],"related":["tc-99m","technetium-sulfur-colloid","tilmanocept-tc99m"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","radionuclide-generators-kits","therapy-isotope-supply-chain","spect"],"targets":[],"drugs":[],"companies":["curium","ire","ansto","ntp-radioisotopes","northstar-medical-radioisotopes","nordion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"99Mo","element":"Molybdenum","massNumber":99,"halfLife":"65.94 hours (2.75 days)","emissions":["β− (multiple transitions, max ~1.36 MeV)","γ (from 99mTc daughter, 140.5 keV)"],"emissionClass":"beta-minus","use":"imaging","production":"Reactor: fission of highly enriched or low-enriched uranium-235 targets, or neutron activation of enriched/natural molybdenum-98, 98Mo(n,γ)99Mo (used by NorthStar's RadioGenix System).","supply":"constrained","supplyNote":"Roughly 95% of global supply still comes from a handful of ageing research reactors (BR2, HFR, LVR-15, Maria, SAFARI-1 and others); the October 2024 unplanned HFR shutdown combined with scheduled maintenance elsewhere to cause supply strain, and the underlying OECD/NEA-documented problem is decades of underinvestment against a fleet that was not designed for continuous production. HEU-to-LEU target conversion is essentially complete (Curium, January 2018; IRE, March 2023; more than 90% of global bulk 99Mo from non-HEU sources by 2023) but LEU targets are less efficient.","chelators":[],"pairedWith":["tc-99m"],"since":1958,"route":"/isotopes/mo-99/"}
{"id":"ge-68","kind":"isotope","name":"Germanium-68","aka":["68Ge","Ge-68"],"tldr":"The long-lived parent locked inside a gallium-68 generator. One loaded column can supply a year's worth of PET tracer doses for prostate cancer and neuroendocrine tumour scans, but the generators themselves have been expensive and slow to get.","summary":"Germanium-68 decays by electron capture with a 270.8-day (about 9-month) half-life, far too long to be imaged usefully itself; its entire clinical role is as the parent bound inside a 68Ge/68Ga generator column, decaying continuously to the 68-minute daughter gallium-68 that is eluted with dilute acid for use in PET tracers such as 68Ga-DOTATATE and 68Ga-PSMA-11. Because the parent's half-life is roughly 5,800 times the daughter's, a single generator loaded with germanium-68 supplies a fairly constant, though slowly declining, stream of gallium-68 for around a year before it needs replacing.\n\nGermanium-68 itself is made almost exclusively by high-energy proton bombardment of a gallium metal target enriched in the stable isotope gallium-69, via the 69Ga(p,2n)68Ge reaction; because commercial-scale generator loadings require tens of gigabecquerels of activity and the reaction needs proton energies of roughly 20-30 MeV over several days of irradiation at high beam current, only a small number of high-energy cyclotron and accelerator facilities worldwide can produce it (an alternative 66Zn(alpha,2n)68Ge route using alpha-particle beams exists but is less commonly used).\n\nThat narrow production base is why 68Ge/68Ga generator supply has repeatedly lagged clinical demand: GMP-grade generator lead times ran as long as 18 months in the years before the 2016-2020 approvals of gallium-68 DOTATATE and PSMA-11 PET agents, and a 2017 shortage of germanium feedstock further squeezed availability, prompting the IAEA in 2019-2020 to promote direct cyclotron production of gallium-68 (68Zn(p,n)68Ga) as a way to sidestep the germanium-68 bottleneck altogether rather than solve it. Manufacturers including Eckert & Ziegler subsequently expanded generator manufacturing capacity, and by the mid-2020s most large PET centres have access to either generator- or cyclotron-produced gallium-68, though the underlying germanium-68 production base remains concentrated in a handful of accelerator facilities.","status":"established","asOf":"2026-09-22","links":[{"label":"PMC: good practices for 68Ga radiopharmaceutical production (68Ge production section)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9588110/"},{"label":"Wikipedia: gallium-68 generator (68Ge production routes)","url":"https://en.wikipedia.org/wiki/Gallium-68_generator"},{"label":"IAEA: new CRP on cyclotron-based gallium-68 (2020)","url":"https://www.iaea.org/newscenter/news/new-crp-production-of-cyclotron-based-gallium-68-radioisotope-and-related-radiopharmaceuticals-f22073"}],"tags":["generator parent","long-lived","supply bottleneck"],"related":["ga-68","ga68-dotatate","ga68-psma-11"],"indications":[],"sections":[],"technologies":["radionuclide-generators-kits","sstr-pet","psma-pet","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":["eckert-ziegler","ire","isotopia"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"68Ge","element":"Germanium","massNumber":68,"halfLife":"270.8 days","emissions":["electron capture (decays to 68Ga)"],"emissionClass":"gamma","use":"imaging","production":"Cyclotron: 69Ga(p,2n)68Ge on gallium metal target enriched in gallium-69, requiring proton energies of roughly 20-30 MeV and multi-day, high-current irradiation; alternative 66Zn(alpha,2n)68Ge route with alpha-particle beams.","supply":"tight","supplyNote":"Production is concentrated at a small number of high-energy accelerator facilities because commercial generator loadings need irradiations of tens of thousands of microamp-hours; GMP generator lead times reached about 18 months before the PSMA PET launch, and a 2017 germanium feedstock shortage further tightened supply. IAEA-promoted direct cyclotron production of gallium-68 bypasses this bottleneck rather than resolving it.","chelators":[],"pairedWith":["ga-68"],"since":1960,"route":"/isotopes/ge-68/"}
{"id":"lu-177","kind":"isotope","name":"Lutetium-177","aka":["177Lu","Lu-177"],"tldr":"A radioactive metal that gives off short-range radiation. Attached to a molecule that sticks to a tumour, it irradiates the tumour from the inside while sparing most healthy tissue.","summary":"Lutetium-177 is the workhorse therapeutic radionuclide of the theranostic era, carried by DOTATATE (Lutathera, neuroendocrine tumours) and PSMA-617 (Pluvicto, prostate cancer). Its 6.65-day half-life and roughly 0.5-2 mm beta range let it be shipped internationally and deliver a dose that matches small-to-medium tumour deposits.\n\nIts 208 keV gamma emission is imageable, so the same injection that treats the patient can be used for post-therapy SPECT and dosimetry. It can be made carrier-added by direct neutron capture on 176Lu, or no-carrier-added (higher specific activity) via 176Yb(n,γ)177Yb, which decays to 177Lu; the latter avoids the long-lived 177mLu impurity but needs scarce enriched 176Yb.\n\nDemand rose sharply after Pluvicto's 2022 approval, straining the small number of high-flux research reactors (BR2, HFR, Maria, SAFARI-1 and others) and the Russian-dominated supply of enriched ytterbium-176. Shortages in 2022-2023 delayed some Pluvicto doses; new capacity (Bruce Power/Isogen in Canadian CANDU reactors, SHINE's accelerator route) has since expanded supply.","status":"approved","asOf":"2026-09-22","links":[{"label":"Challenges and future options for the production of lutetium-177 (EJNMMI Radiopharm Chem, 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8241800/"},{"label":"FDA label: Pluvicto (lutetium Lu 177 vipivotide tetraxetan)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf"},{"label":"OECD-NEA: Current trends in the supply and utilisation of medical radioisotopes (2025)","url":"https://www.oecd-nea.org/upload/docs/application/pdf/2025-10/7743_medical_radioisotopes_supply_rev.pdf"}],"tags":["therapy","beta emitter"],"related":["pluvicto","lutathera","prrt","lu177-radioligand-therapy","therapy-isotope-supply-chain"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"177Lu","element":"Lutetium","massNumber":177,"halfLife":"6.65 days","emissions":["β− 497 keV maximum (mean 134 keV)","γ 113 keV (6.2%)","γ 208 keV (10.4%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Up to about 2 mm, mean roughly 0.5-0.7 mm","production":"Reactor. Non-carrier-added via 176Yb(n,γ)177Yb, which beta-decays to 177Lu; or carrier-added via direct 176Lu(n,γ)177Lu (co-produces long-lived 177mLu).","supply":"tight","supplyNote":"Demand rose sharply after Pluvicto's approval. Reactor neutron-flux capacity and the scarcity of enriched 176Yb (historically mostly from Russian calutrons) are the binding constraints; new capacity from Bruce Power/Isogen (Canada) and accelerator routes (SHINE) is scaling up.","chelators":["DOTA","DOTAGA"],"pairedWith":["ga-68"],"since":2018,"route":"/isotopes/lu-177/"}
{"id":"ac-225","kind":"isotope","name":"Actinium-225","aka":["225Ac","Ac-225"],"tldr":"A metal that fires off very powerful, very short-range radioactive particles as it decays through a chain of daughter atoms. Because the particles barely travel beyond the cell they hit, it can kill a cancer cell while leaving neighbouring healthy cells mostly untouched. Supply is scarce, so it is still mostly used in research studies.","summary":"Actinium-225 decays by alpha emission through six short-lived daughters to stable bismuth-209, releasing a net four alpha particles per decay (a 'nanogenerator'). At 9.9 days its half-life is long enough for centralised manufacture and international shipping, unlike its short-lived daughter bismuth-213.\n\nThe historical route extracts 225Ac from decaying stockpiles of thorium-229 (itself from aged uranium-233), 'milked' every few weeks; the amounts are milligram/curie-scale and cannot be scaled much further. Newer accelerator routes -- proton spallation of thorium-232, or proton irradiation of radium-226 targets via 226Ra(p,2n)225Ac -- are being industrialised by the DOE's Tri-Lab effort (Brookhaven, Los Alamos, Oak Ridge) and by companies building cyclotron and linac capacity.\n\nSupply is the most contested number in the field. A 2023 Journal of Nuclear Medicine analysis put worldwide 229Th/225Ac-derived supply at roughly 63 GBq (1.7 Ci) per year, enough for only 100-200 patients, against a stated need for hundreds to thousands of curies a year if approved 225Ac drugs reach broad use; it projected accelerator and photonuclear routes could reach over 25 TBq (670 Ci) a year worldwide by 2032. Other DOE and IAEA figures from 2013-2021 cite current 229Th-derived supply at 1-2 Ci/year (37-74 GBq) split mainly between Oak Ridge National Laboratory (ORNL, USA), the Joint Research Centre in Karlsruhe (Germany, ~13 GBq/year) and IPPE Obninsk (Russia, ~22 GBq/year), and note the same production facilities co-produce the long-lived impurity 227Ac (half-life 21.8 years) at the 0.1-0.2% level, which complicates waste handling and dosimetry.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Is Actinium Really Happening? (Journal of Nuclear Medicine, 2023)","url":"https://jnm.snmjournals.org/content/64/10/1516"},{"label":"DOE Isotope Program: Production Methods for Ac-225","url":"https://www.isotopes.gov/information/actinium-225"},{"label":"Supply and Clinical Application of Actinium-225 and Bismuth-213 (PMC, 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7082773/"},{"label":"Actinium-225 in targeted alpha-particle therapeutic applications (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5565267/"}],"tags":["therapy","alpha emitter","supply-constrained"],"related":["ac225-psma","ryz101","fpi-2265","targeted-alpha-therapy","actinium-225-supply","idea-reg-ac225-accelerator-pharmacopoeia","idea-reg-legacy-radium-recovery-ac225","bi-213"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"225Ac","element":"Actinium","massNumber":225,"halfLife":"9.92 days","emissions":["α 5.8 MeV (225Ac itself)","α, β and γ from the six-member decay chain to stable 209Bi (net 4 α, 3 β, 2 useful γ per decay)"],"emissionClass":"alpha","use":"therapy","tissueRange":"A few cell diameters (tens of micrometres)","production":"Decay of parent 229Th stockpiles ('milked' periodically), or accelerator: proton spallation of 232Th, or cyclotron 226Ra(p,2n)225Ac.","supply":"constrained","supplyNote":"Disputed. JNM (2023) estimated current 229Th-derived worldwide supply at ~63 GBq (1.7 Ci)/year, enough for 100-200 patients/year, versus a need in the hundreds-to-thousands of Ci/year for broad approval; it projected >25 TBq (670 Ci)/year of installed capacity worldwide by 2032 from accelerator and photonuclear routes. Earlier DOE/IAEA figures (2013-2021) put current 229Th/225Ac supply at roughly 1.2-1.7 Ci/year split between ORNL (USA), JRC Karlsruhe (Germany) and IPPE Obninsk (Russia).","chelators":["DOTA","macropa"],"pairedWith":["ga-68"],"route":"/isotopes/ac-225/"}
{"id":"ra-223","kind":"isotope","name":"Radium-223","aka":["223Ra","Ra-223"],"tldr":"A radioactive form of the mineral radium that behaves like calcium and settles into bone. It gives off very short-range, high-energy particles that damage cancer growing in bone while barely reaching the healthy marrow next to it.","summary":"Radium-223 dichloride (Xofigo) is a calcium mimetic that concentrates in areas of increased bone turnover, such as osteoblastic bone metastases. It decays through a six-stage chain to stable lead-207, emitting predominantly alpha particles (95.3% of emitted energy), with small beta (3.6%) and gamma (1.1%) contributions from itself and its short-lived daughters (polonium-215, lead-211, bismuth-211, thallium-207).\n\nThe alpha range is under 100 micrometres in tissue (maximum about 6.2 cm in air), so the dose is deposited within roughly the width of a few cells of the bone surface, largely sparing the adjacent marrow. It was the first alpha-emitting radiopharmaceutical to gain FDA and EMA approval, on the strength of the ALSYMPCA trial's overall-survival benefit in metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral disease.\n\nRa-223 is obtained from a generator chain rooted in actinium-227 (itself made by neutron irradiation of radium-226 in a reactor); Ac-227 beta-decays to thorium-227, which alpha-decays to Ra-223. Commercial-scale 223Ra is available from Bayer's own supply chain and, more broadly, ORNL, PNNL and Rosatom hold production capability; a 2025 review (the PSI-led 'Alpha Atlas') judged that, unlike most other alpha emitters, 223Ra supply is adequate to global demand and no near-term shortage is expected.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Xofigo (radium Ra 223 dichloride)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203971lbl.pdf"},{"label":"Radium-223 mechanism of action (Nature Reviews Urology, 2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7515774/"},{"label":"Production and supply of alpha particle emitting radionuclides for TAT (JNM, 2021)","url":"https://jnm.snmjournals.org/content/jnumed/early/2021/07/22/jnumed.120.261016.full.pdf"},{"label":"Alpha Atlas: mapping global production of alpha-emitting radionuclides for TAT (PSI, 2025)","url":"https://www.dora.lib4ri.ch/psi/islandora/object/psi:68199/datastream/PDF/Tosato-2025-Alpha_Atlas-(published_version).pdf"}],"tags":["therapy","alpha emitter","bone-seeking"],"related":["radium-223","alsympca","paper-alsympca-radium-223-nejm-2013","bone-metastases","th-227","targeted-alpha-therapy"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"223Ra","element":"Radium","massNumber":223,"halfLife":"11.4 days","emissions":["α (95.3% of emitted energy, range 5-7.5 MeV)","β− (3.6%, average 0.445 and 0.492 MeV)","γ (1.1%, 0.01-1.27 MeV range)"],"emissionClass":"alpha","use":"therapy","tissueRange":"Under 100 micrometres in tissue; up to 6.2 cm in air","production":"Generator chain from reactor-made actinium-227 (226Ra(n,γ)227Ra → β− → 227Ac), which beta-decays to 227Th, which alpha-decays to 223Ra.","supply":"adequate","supplyNote":"223Ra is judged adequately supplied worldwide; Bayer is the primary commercial supplier, with ORNL, PNNL and Rosatom also holding production capability for 223Ra and its 227Th parent.","chelators":[],"pairedWith":[],"since":2013,"route":"/isotopes/ra-223/"}
{"id":"i-131","kind":"isotope","name":"Iodine-131","aka":["131I","I-131","radioiodine"],"tldr":"A radioactive form of iodine. Because the thyroid gland naturally absorbs iodine, swallowing it lets the radiation destroy thyroid cells or thyroid cancer cells almost anywhere they have spread, with very little effect on the rest of the body.","summary":"Iodine-131 decays by beta emission with an associated gamma emission and a physical half-life of 8.02-8.04 days. Its principal beta emissions average around 190 keV with higher-energy components up to roughly 606 keV, and the dominant imaging gamma is 364.5 keV (about 81% abundance); roughly 90% of local irradiation from sodium iodide I-131 comes from the beta component and 10% from gamma, per the FDA label.\n\nBecause thyroid follicular cells and well-differentiated thyroid cancer retain the sodium/iodide symporter, oral 131I concentrates selectively in thyroid tissue, remnant tissue after thyroidectomy, and iodine-avid metastases, delivering an internal beta dose. It has been used for benign thyroid disease and differentiated thyroid cancer ablation for more than 70 years and remains a WHO essential medicine.\n\nCommercial 131I is produced in a nuclear reactor overwhelmingly by neutron activation of tellurium-130 (130Te(n,γ)131Te/131mTe, which beta-decays to 131I), recovered by dry or wet distillation; it can also be recovered as a uranium-235 fission product, though current suppliers do not routinely co-recover it that way. As a widely produced, long-established reactor product with many qualified suppliers, supply is generally adequate, though individual reactor outages can cause local shortages.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Sodium Iodide I-131 Solution (therapeutic)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016517s016lbl.pdf"},{"label":"FDA label: Sodium Iodide I 131 Capsules (diagnostic)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021305s041lbl.pdf"},{"label":"Medical Isotope Production and Utilization (NAS/NCBI, 2016)","url":"https://www.ncbi.nlm.nih.gov/books/NBK396163/"}],"tags":["therapy","beta emitter","gamma emitter"],"related":["radioactive-iodine","radioiodine-therapy","i131-mibg","iobenguane-i-131","thyroid","estimabl2","radioiodine-term"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"131I","element":"Iodine","massNumber":131,"halfLife":"8.02 days","emissions":["β (mean 191.6 keV, 89.9%; smaller components at 69.4 and 96.6 keV)","γ 364.5 keV (81.2%)","γ 637.0 keV (7.2%)","γ 284.3 keV (6.1%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"A few millimetres (beta range)","production":"Reactor: neutron activation of tellurium-130, 130Te(n,γ)131Te (or 131mTe), which beta-decays to 131I; historically also recoverable as a 235U fission product.","supply":"adequate","supplyNote":"Long-established reactor product made by many qualified international suppliers via Te-130 activation; generally adequate, though reactor outages can cause transient regional shortages.","chelators":[],"pairedWith":["i-123","i-124"],"since":1946,"route":"/isotopes/i-131/"}
{"id":"y-90","kind":"isotope","name":"Yttrium-90","aka":["90Y","Y-90"],"tldr":"A radioactive metal that fires high-energy particles a short distance into surrounding tissue. Millions of microscopic beads carrying it are injected into the artery feeding a liver tumour, where they lodge and irradiate the tumour from inside.","summary":"Yttrium-90 is a near-pure beta emitter (a small pair-production fraction allows PET imaging of its distribution) that decays to stable zirconium-90 with a physical half-life of 64.1 hours (2.67 days). Its beta particles have a mean energy near 0.93-0.94 MeV, a mean tissue range of about 2.5 mm and a maximum of roughly 11 mm, and 94% of the total dose is delivered within about 11 days.\n\nIt is the workhorse isotope of liver radioembolisation (TARE/SIRT): glass microspheres (TheraSphere) with 90Y built into the glass matrix, and resin microspheres (SIR-Spheres) with 90Y bound to the surface, are delivered via a hepatic-artery catheter and become permanently embedded in and around the tumour. It is also used, chelated to peptides and antibodies, for radioligand and radioimmunotherapy (e.g. ibritumomab tiuxetan).\n\n90Y for microsphere manufacture is produced either by decay of its 28.8-year fission-product parent strontium-90 (chemically separated as it decays) or by direct reactor neutron activation of stable yttrium-89. Because the parent Sr-90/generator route and direct reactor activation are both well established at multiple sites, supply for the approved microsphere products is generally adequate.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA PMA summary: TheraSphere Yttrium-90 Glass Microspheres","url":"https://www.accessdata.fda.gov/cdrh_docs/pdf20/P200029C.pdf"},{"label":"The development, commercialization, and clinical context of yttrium-90 (PMC, 2016)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5514171/"},{"label":"Yttrium-90 Radioembolization Dosimetry: What Trainees Need to Know (PMC, 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7732571/"}],"tags":["therapy","beta emitter","radioembolisation"],"related":["radioembolisation-tare","tare","hcc","hcc-intermediate","ibritumomab-tiuxetan","sirtex","boston-scientific"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"90Y","element":"Yttrium","massNumber":90,"halfLife":"64.1 hours (2.67 days)","emissions":["β− average 0.93-0.94 MeV, maximum 2.28 MeV"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Mean about 2.5 mm, maximum about 11 mm","production":"Decay of fission-product parent 90Sr (chemically separated on decay), or direct reactor neutron activation of stable 89Y, 89Y(n,γ)90Y.","supply":"adequate","supplyNote":"Available from established 90Sr/90Y separation and direct reactor-activation routes at multiple sites supplying the two FDA-approved microsphere products.","chelators":["DOTA"],"pairedWith":["tc-99m"],"route":"/isotopes/y-90/"}
{"id":"pb-212","kind":"isotope","name":"Lead-212","aka":["212Pb","Pb-212"],"tldr":"A radioactive metal that, once inside the body, turns itself into a much more damaging particle-emitter over the following hours. It is being explored as a way to deliver strong, short-range radiation without needing the rarer isotopes used in similar treatments.","summary":"Lead-212 is itself a beta emitter, but it functions in practice as an in vivo generator of alpha radiation: it decays (half-life 10.64 hours) to bismuth-212 (half-life about 61 minutes), which then decays either directly by alpha emission (to thallium-208) or by a further beta decay to the pure alpha emitter polonium-212. A member of the thorium-232/232U decay series, 212Pb is drawn from generators loaded with its longer-lived parents radium-224 (half-life 3.63 days) or thorium-228 (half-life about 1.9 years).\n\nIts 10.6-hour half-life is long enough to synthesise and ship a labelled radiopharmaceutical but short enough to limit prolonged radiation exposure, and it uses conventional chelation chemistry (unlike some other alpha emitters). 212Pb-DOTAMTATE (AlphaMedix) and other 212Pb-labelled somatostatin and PSMA-targeting agents are in early clinical trials.\n\nUnlike actinium-225, the feedstock chain for 212Pb (natural thorium-232/uranium-232 decay) is not considered scarce: Perspective Therapeutics states its proprietary 224Ra/212Pb generator system and a long-term US DOE supply contract for 228Th could support over 100,000 doses per year, and Orano Med, RadioMedix/Thor Medical and others are commercialising 228Th-based 212Pb generators. Some reviews describe 212Pb supply as having moved from a major constraint to a largely solved production problem, though clinical-scale, GMP-qualified generator throughput is still being industrialised.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"212Pb: Production Approaches and Targeted Therapy Applications (Pharmaceuticals, 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8777968/"},{"label":"Perspective Therapeutics: Manufacturing & Logistics (VMT-α-GEN Pb-212 generator)","url":"https://perspectivetherapeutics.com/technology/manufacturing-logistics"},{"label":"DOE Isotope Program: Availability of radium-224/lead-212 generators","url":"https://www.isotopes.gov/node/123"},{"label":"Lead radionuclides for theranostic applications in nuclear medicine (PMC, 2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12775822/"}],"tags":["therapy","alpha emitter","in vivo generator"],"related":["alphamedix","alphamedix-02","targeted-alpha-therapy","ra-224","bi-213","idea-reg-alpha-emitter-portfolio","perspective-therapeutics"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"212Pb","element":"Lead","massNumber":212,"halfLife":"10.64 hours","emissions":["β− 0.57 MeV (to 212Bi)","in vivo daughter 212Bi decays 35.9% by α to 208Tl, 64.1% by β− to 212Po","212Po α 8.78 MeV (from 212Bi decay)"],"emissionClass":"mixed","use":"therapy","tissueRange":"Sub-millimetre (alpha range from in-vivo-generated 212Bi/212Po)","production":"Generator: eluted from 224Ra or 228Th sources (228Th itself recovered from decaying 232U stocks), via 220Rn emanation or column separation.","supply":"emerging","supplyNote":"Feedstock (natural thorium-232/232U decay) is not scarce. Perspective Therapeutics reports a long-term DOE supply contract for 228Th and generator capacity aimed at over 100,000 doses/year; Orano Med, Telix and RadioMedix/Thor Medical are also commercialising 228Th/224Ra-based 212Pb generators, but clinical-scale GMP throughput is still being built out.","chelators":["DOTAM","DOTAMTATE-type macrocycles"],"pairedWith":["ga-68"],"route":"/isotopes/pb-212/"}
{"id":"bi-213","kind":"isotope","name":"Bismuth-213","aka":["213Bi","Bi-213"],"tldr":"An extremely short-lived radioactive metal that delivers a powerful, very local burst of radiation. Because it decays away within a few hours, it has to be made freshly at the hospital, right before it is given to the patient.","summary":"Bismuth-213 is a daughter of actinium-225 with a half-life of only 45.6 minutes. It decays by branching: about 97.8% by beta emission to the ultra-short-lived pure alpha emitter polonium-213 (half-life about 4 microseconds), and a small fraction (roughly 2%) directly by alpha emission to thallium-209. Around 92-93% of the energy released per 213Bi decay is ultimately carried by alpha particles.\n\nBecause its half-life is far shorter than any other clinical radiotherapeutic isotope, 213Bi cannot be centrally manufactured and shipped; it is produced on demand from a 225Ac/213Bi radionuclide generator, typically eluted every two to three hours in clinical use, giving elution yields around 83-93%. The main generator design (an AG MP-50 cation-exchange resin loaded with 225Ac) was pioneered at the Joint Research Centre in Karlsruhe, Germany, which has supplied it free of charge for clinical trials in Europe and the US.\n\n213Bi shares essentially all of 225Ac's supply constraints, since it is milked from the same scarce 225Ac stock, and using it consumes 225Ac less efficiently per alpha particle delivered than using 225Ac directly (only the final alpha of the decay chain is captured). It has been used in early-phase trials in leukaemia, glioma, melanoma, bladder cancer, lymphoma and neuroendocrine tumours, most with anti-CD33 or similar targeting constructs, but has not reached late-phase development.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Bismuth-213 for Targeted Radionuclide Therapy (Pharmaceutics, 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8143329/"},{"label":"Actinium-225/Bismuth-213 as Potential Leaders for Targeted Alpha Therapy (Pharmaceutics, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12468084/"},{"label":"Bismuth-213 and Actinium-225 - Generator Performance (Current Radiopharmaceuticals, 2012)","url":"https://www.ingentaconnect.com/content/ben/crp/2012/00000005/00000003/art00006"}],"tags":["therapy","alpha emitter","generator-produced","short-lived"],"related":["ac-225","targeted-alpha-therapy","idea-reg-alpha-emitter-portfolio"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"213Bi","element":"Bismuth","massNumber":213,"halfLife":"45.6 minutes","emissions":["β− 444 keV (97.84%, to 213Po)","α 5.55-5.87 MeV (about 2%, direct to 209Tl)","213Po α 8.375 MeV in vivo (from the β− branch)","γ 440 keV (usable for imaging)"],"emissionClass":"mixed","use":"therapy","tissueRange":"40-80 micrometres (alpha range)","production":"Generator: eluted from a 225Ac/213Bi radionuclide generator (cation-exchange resin loaded with 225Ac), typically every 2-3 hours.","supply":"constrained","supplyNote":"Entirely dependent on the same scarce 225Ac supply (see ac-225); the JRC Karlsruhe 225Ac/213Bi generator has been the main clinical-trial source in Europe and the US, supplied without charge for research use.","chelators":["DTPA-based bifunctional chelators","CHX-A''-DTPA"],"pairedWith":["ga-68"],"route":"/isotopes/bi-213/"}
{"id":"at-211","kind":"isotope","name":"Astatine-211","aka":["211At","At-211"],"tldr":"A radioactive halogen, chemically similar to iodine, that gives off a single powerful short-range particle as it decays. It has to be made in a particular kind of accelerator and used within hours, which is why only a handful of centres worldwide can supply it.","summary":"Astatine-211 decays with a 7.2-hour half-life entirely by alpha emission, branching between two paths: about 41.8% via direct alpha emission to long-lived 207Bi, and about 58.2% via alpha decay to 211Po (half-life 0.52 s), which itself alpha-decays to stable 207Pb. Because astatine sits in the halogen group, it can in principle use much of the same radiochemistry developed for radioiodine (e.g. astato-benzylguanidine as an analogue of iobenguane).\n\nIt is made almost exclusively by bombarding natural, monoisotopic bismuth-209 targets with alpha particles in a cyclotron via the 209Bi(α,2n)211At reaction, which requires a beam of around 28-29.5 MeV; energies above this range increasingly co-produce the long-lived, more radiotoxic contaminant 210At (which decays to 210Po), so machines are tuned to stay just below or at that threshold.\n\nSupply is the binding constraint: as of the mid-2020s only a handful of cyclotrons worldwide routinely produce clinical-grade 211At, including Copenhagen (Denmark), Arronax in Nantes (France), Duke University, the University of Washington and Ionetix (Michigan, first US commercial supplier, shipping since September 2026) in the US, with new or restarting capacity in Poland, Czechia, the UK and South Korea. Because of the 7.2-hour half-life, 211At must be produced close to where it will be used and cannot be stockpiled or shipped over long distances.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Astatine-211: Production and Availability (Curr Radiopharm, PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3503149/"},{"label":"Solving the limited availability of Astatine-211 from a European perspective (PMC, 2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12929731/"},{"label":"Ionetix: Ionetix Begins Shipping Astatine-211 to Support Preclinical and Clinical Trials (2026)","url":"https://ionetix.com/2026/09/01/ionetix-begins-shipping-astatine-211-to-support-preclinical-and-clinical-trials/"}],"tags":["therapy","alpha emitter","halogen","supply-constrained"],"related":["astatine-211-alpha-therapy","targeted-alpha-therapy","cyclotron-isotope-production","idea-reg-alpha-emitter-portfolio"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"211At","element":"Astatine","massNumber":211,"halfLife":"7.21 hours","emissions":["α 5.87 MeV (41.8%, to 207Bi)","α 7.45 MeV (58.2%, via 211Po to stable 207Pb)"],"emissionClass":"alpha","use":"therapy","tissueRange":"Tens of micrometres (alpha range)","production":"Cyclotron: alpha-particle bombardment of natural bismuth-209 targets, 209Bi(α,2n)211At, at about 28-29.5 MeV.","supply":"research-only","supplyNote":"Requires a medium-energy (~28-30 MeV) alpha-beam cyclotron; only a handful of sites worldwide (Copenhagen, Arronax/Nantes, Duke, University of Washington, and since 2026 Ionetix in Michigan as the first US commercial supplier) produce it routinely, and its 7.2-hour half-life rules out long-distance shipping.","chelators":[],"pairedWith":["i-123"],"route":"/isotopes/at-211/"}
{"id":"tb-161","kind":"isotope","name":"Terbium-161","aka":["161Tb","Tb-161"],"tldr":"A radioactive metal, chemically almost identical to the widely-used lutetium-177, that gives off the same kind of medium-range particles plus a burst of extra very-short-range electrons. Those extra electrons may let it do more damage to a cancer cell than lutetium-177 while using the same delivery molecules.","summary":"Terbium-161 decays by beta-minus emission with a half-life of 6.95 days (very close to lutetium-177's 6.65 days) to stable dysprosium-161, and shares much of 177Lu's chemistry (both are trivalent lanthanides suited to DOTA-type chelators), so it can be substituted directly into existing DOTATATE, DOTATOC and PSMA-617-type ligands.\n\nWhat distinguishes it is a large yield of low-energy conversion and Auger electrons -- roughly 2.3 electrons above 3 keV per decay, with ranges from nanometres to a few tens of nanometres -- alongside its 154 keV mean-energy beta particles, which give it a mean tissue range similar to 177Lu (about 0.7 mm) but potentially more damage to single cells and micrometastases through the additional short-range electrons. It also emits imageable gamma/X-rays around 48.9 keV (17%) and 74.6 keV (10%), suitable for SPECT, including simultaneous dual-isotope imaging alongside 177Lu.\n\nProduction is analogous to no-carrier-added 177Lu: thermal-neutron irradiation of enriched gadolinium-160 targets produces short-lived 161Gd (half-life 3.66 minutes), which beta-decays to 161Tb; the Tb is then chemically separated from the bulk Gd. It therefore depends on the same high-flux research reactors used for 177Lu (a European PRISMAP network of ILL, SCK CEN and NCBJ reactors, plus PSI's SINQ spallation source, and a University of Utah TRIGA/University of Missouri collaboration in the US), and remains available only in gigabecquerel, research-scale monthly batches. Terbium-161-labelled PSMA and somatostatin-receptor agents are in early clinical investigation and are not approved by the FDA or EMA.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Opportunities and potential challenges of using terbium-161 (Eur J Nucl Med Mol Imaging, 2023)","url":"https://link.springer.com/article/10.1007/s00259-023-06316-y"},{"label":"Potentials and practical challenges of terbium-161 labeled radiopharmaceuticals (PMC, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12494511/"},{"label":"DOE/isotopes.gov: To Advance Cancer Therapy, University Starts Producing Tb-161","url":"https://www.isotopes.gov/node/1517"},{"label":"PRISMAP: 161Tb radionuclide portfolio page","url":"https://www.prismap.eu/radionuclides/portfolio/161Tb/"}],"tags":["therapy","beta emitter","auger electron emitter","research-only"],"related":["lu-177","prrt","idea-reg-alpha-emitter-portfolio","auger-electron-therapy"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"161Tb","element":"Terbium","massNumber":161,"halfLife":"6.95 days","emissions":["β− mean 154 keV (to stable 161Dy)","conversion + Auger electrons (~2.27 per decay, >3 keV)","γ/X-ray 48.9 keV (17%)","γ/X-ray 74.6 keV (10.2%)"],"emissionClass":"mixed","use":"therapy","tissueRange":"Mean about 0.7 mm (beta), plus nanometre-to-tens-of-nanometre range from Auger/conversion electrons","production":"Reactor: thermal-neutron irradiation of enriched gadolinium-160, 160Gd(n,γ)161Gd, which beta-decays (t1/2 3.66 min) to 161Tb; chemically separated from the Gd target.","supply":"research-only","supplyNote":"Produced at gigabecquerel, monthly-batch scale by the European PRISMAP network (ILL, SCK CEN, NCBJ reactors; PSI's SINQ) and by a University of Utah/University of Missouri TRIGA-reactor collaboration; not yet available at Lu-177-scale clinical supply.","chelators":["DOTA","DOTATATE/DOTATOC-type macrocycles"],"pairedWith":["ga-68"],"route":"/isotopes/tb-161/"}
{"id":"cu-67","kind":"isotope","name":"Copper-67","aka":["67Cu","Cu-67"],"tldr":"A radioactive form of copper that pairs with a diagnostic twin made of the same element, copper-64. Using the same metal for the scan and the treatment means the tracer behaves identically both times, which should make dosing more predictable.","summary":"Copper-67 decays purely by beta-minus emission with a physical half-life of 61.8-62 hours (about 2.58 days) to stable zinc-67, with a mean beta energy of about 141 keV (maximum energies at 377, 468 and 562 keV) and useful imaging gammas at 93 keV and 184.6 keV (about 49% abundance), which support SPECT-based dosimetry.\n\nIts principal theranostic appeal is chemical identity with copper-64, the positron-emitting isotope used for PET imaging of the same chelator-conjugated agent (e.g. SAR-bisPSMA, SARTATE): the same molecule with the same biodistribution can be imaged pre-therapy with 64Cu and then dosed with 67Cu, avoiding the surrogate mismatch inherent in most other theranostic pairs.\n\nProduction historically used reactor or lower-energy cyclotron reactions (67Zn(n,p)67Cu, 68Zn(p,2p)67Cu, 70Zn(p,α)67Cu), each limited to modest specific activity. A step change came from high-energy bremsstrahlung photonuclear production, 68Zn(γ,p)67Cu, using electron linear accelerators to irradiate enriched 68Zn targets; the US Department of Energy Isotope Program's Low Energy Accelerator Facility (LEAF) uses this route to supply no-carrier-added 67Cu at specific activities above 1850 GBq/mg. Clarity Pharmaceuticals and the DOE Isotope Program are among the groups scaling supply; 67Cu is not dependent on nuclear reactor neutron flux, so it avoids the reactor-capacity bottleneck that constrains 177Lu and 225Ac.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Recent Advances in 64Cu/67Cu-Based Radiopharmaceuticals (Pharmaceutics, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10288943/"},{"label":"67Cu Production Capabilities: A Mini Review (Front Med, 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8912090/"},{"label":"Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT (Scientific Reports, 2021)","url":"https://www.nature.com/articles/s41598-021-82812-1"},{"label":"Clarity Pharmaceuticals: Copper-64 and Copper-67 - The Perfect Theranostic Pairing","url":"https://www.claritypharmaceuticals.com/technology/copper-isotopes/"}],"tags":["therapy","beta emitter","theranostic pair"],"related":["nct04868604","nct06298916","clarity-pharmaceuticals","cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"67Cu","element":"Copper","massNumber":67,"halfLife":"61.8 hours (2.58 days)","emissions":["β− mean 141 keV (maxima 377/468/562 keV)","γ 93.3 keV (7-16%)","γ 184.6 keV (~49%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"About 0.7 mm mean (comparable to 177Lu)","production":"Accelerator: bremsstrahlung photonuclear reaction on enriched zinc-68, 68Zn(γ,p)67Cu, using an electron linear accelerator; also reactor 67Zn(n,p)67Cu or cyclotron 68Zn(p,2p)67Cu / 70Zn(p,α)67Cu.","supply":"emerging","supplyNote":"The photonuclear 68Zn(γ,p)67Cu route (US DOE Isotope Program's LEAF facility) yields high-specific-activity, no-carrier-added 67Cu without needing reactor neutron flux, easing the bottlenecks that affect 177Lu and 225Ac; supply is scaling but still limited relative to established isotopes.","chelators":["SarAr/SAR-type sarcophagine cages","DOTA"],"pairedWith":["cu-64"],"route":"/isotopes/cu-67/"}
{"id":"sm-153","kind":"isotope","name":"Samarium-153","aka":["153Sm","Sm-153"],"tldr":"A radioactive metal, given as an injection, that homes in on the actively growing edges of bone and gives off radiation there. It is used to ease pain from cancer that has spread to bone.","summary":"Samarium-153 lexidronam (Quadramet, 153Sm-EDTMP) delivers 153Sm chelated to a bone-seeking phosphonate that concentrates roughly five-fold more in osteoblastic lesions than in normal bone. It decays with a physical half-life of 46.3 hours (1.93 days) by emission of three principal beta-particle energies (maxima around 640, 710 and 810 keV; mean beta energy about 233 keV) plus a 103 keV gamma photon (about 28-29% abundance) that permits scintigraphic imaging of biodistribution.\n\nThe beta particles have an average range in soft tissue of roughly 0.5-0.8 mm and a maximum of about 3 mm (about 1.7 mm in bone), similar in scale to other bone-palliation radiopharmaceuticals but with a much shorter half-life than strontium-89, giving faster onset and clearance.\n\n153Sm is produced in high yield and purity by neutron irradiation of isotopically enriched samarium-152 oxide (152Sm2O3) in a reactor, 152Sm(n,γ)153Sm; this is a routine, widely available reactor product and not considered supply-constrained, though Quadramet's US manufacturer has changed hands and availability has fluctuated commercially.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA/manufacturer label: Quadramet (samarium Sm-153 lexidronam) prescribing information","url":"https://www.drugs.com/pro/quadramet.html"},{"label":"EMA: Quadramet EPAR product information","url":"https://www.ema.europa.eu/en/documents/product-information/quadramet-epar-product-information_en.pdf"},{"label":"FDA: comparative physical properties of bone-palliation radiopharmaceuticals (Xofigo NDA review)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203971Orig1s000RiskR.pdf"}],"tags":["therapy","beta emitter","gamma emitter","bone-seeking"],"related":["samarium-153-lexidronam","bone-metastases","sr-89","prostate"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"153Sm","element":"Samarium","massNumber":153,"halfLife":"46.3 hours (1.93 days)","emissions":["β− maxima 640 keV (30%), 710 keV (50%), 810 keV (20%); mean 233 keV","γ 103 keV (~28-29%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Average about 0.5-0.83 mm, maximum about 3 mm in soft tissue","production":"Reactor: neutron irradiation of isotopically enriched samarium-152 oxide, 152Sm(n,γ)153Sm.","supply":"adequate","supplyNote":"Produced routinely by reactor neutron activation of enriched 152Sm; a well-established, non-scarce reactor product, though commercial (Quadramet) availability has seen intermittent supply interruptions unrelated to isotope production capacity.","chelators":["EDTMP"],"pairedWith":["tc-99m"],"since":1997,"route":"/isotopes/sm-153/"}
{"id":"sr-89","kind":"isotope","name":"Strontium-89","aka":["89Sr","Sr-89"],"tldr":"A radioactive metal that behaves like calcium and is taken up by bone, particularly where cancer has spread there. A single injection can ease bone pain for weeks by irradiating those spots from within.","summary":"Strontium-89 chloride (Metastron) is a pure beta emitter, decaying by beta-minus emission with a physical half-life of 50.5 days and a single beta energy of 1.463 MeV (100% abundance), giving a maximum tissue range of roughly 8 mm. Because strontium chemically mimics calcium, it is taken up preferentially into bone at sites of increased osteoblastic activity, such as skeletal metastases, and is retained there far longer than in normal bone -- delivering a prolonged local dose from a single injection, used for palliation of painful bone metastases from prostate and breast cancer.\n\nUnlike samarium-153 or radium-223, 89Sr emits essentially no useful gamma photon, so it cannot be imaged with a gamma camera; patient selection instead typically relies on a separate technetium-99m bone scan.\n\n89Sr is produced by thermal-neutron irradiation of an enriched strontium-88 target, 88Sr(n,γ)89Sr, at the DOE's High Flux Isotope Reactor (Oak Ridge National Laboratory) among other sites, yielding radionuclidic purity above 99.8%. As a long-half-life, well-established reactor product, supply has generally been described by the DOE Isotope Program as steady.","status":"approved","asOf":"2026-09-22","links":[{"label":"FDA label: Metastron (strontium-89 chloride injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020134s012lbl.pdf"},{"label":"DOE Isotope Program: Ensuring a steady supply of strontium-89","url":"https://www.isotopes.gov/Ensuring-steady-supply-of-strontium-89"},{"label":"FDA: comparative physical properties of bone-palliation radiopharmaceuticals (Xofigo NDA review)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203971Orig1s000RiskR.pdf"}],"tags":["therapy","pure beta emitter","bone-seeking"],"related":["bone-metastases","sm-153","ra-223","prostate"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"89Sr","element":"Strontium","massNumber":89,"halfLife":"50.5 days","emissions":["β− 1.463 MeV (100%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Up to about 8 mm","production":"Reactor: thermal-neutron irradiation of enriched strontium-88, 88Sr(n,γ)89Sr.","supply":"adequate","supplyNote":"Produced by neutron capture on enriched 88Sr at high-flux reactors such as ORNL's HFIR; the DOE Isotope Program describes supply as steady, though it is a niche, single-purpose product with few suppliers.","chelators":[],"pairedWith":["tc-99m"],"since":1993,"route":"/isotopes/sr-89/"}
{"id":"ho-166","kind":"isotope","name":"Holmium-166","aka":["166Ho","Ho-166"],"tldr":"A radioactive metal built into tiny beads that are injected into the artery feeding a liver tumour, where they lodge and irradiate it from close range. Unlike similar beads made with yttrium-90, these can also be seen clearly on a scan.","summary":"Holmium-166 poly-L-lactic acid (PLLA) microspheres (QuiremSpheres, QuiremScout) deliver radioembolisation to liver tumours much as yttrium-90 microspheres do, but 166Ho's shorter half-life (26.8 hours) concentrates over 90% of the dose within about 4 days, versus roughly 11 days for 90Y. Its beta spectrum has two main components near 1.77 MeV (48.7%) and 1.85 MeV (50.0%), with a mean tissue range around 2.2-2.5 mm and maximum around 8.7-11 mm, broadly comparable to 90Y.\n\nThe key practical advantage is imageability: 166Ho emits an 81 keV gamma photon (about 6.6-6.7% abundance) suitable for SPECT/CT, and holmium's paramagnetic properties also make the microspheres visible on MRI, so the same product used for a diagnostic 'scout' dose and the therapeutic dose can both be imaged directly, rather than relying on a technetium-99m-labelled surrogate as with 90Y (which requires a separate macroaggregated-albumin lung-shunt scan).\n\n166Ho microspheres are manufactured by first embedding stable holmium-165 in the PLLA polymer matrix, then neutron-activating the finished microspheres in a research reactor (165Ho(n,γ)166Ho); production has run at the BR2 reactor (Belgium) and the Maria reactor (Poland). As a single-manufacturer product (Quirem Medical, part of Terumo) tied to specific reactor irradiation slots, availability is narrower than for 90Y microspheres but has not been reported as a major bottleneck.","status":"approved","asOf":"2026-09-22","links":[{"label":"Holmium-166 Radioembolization: Current Status and Future Perspectives (Cancers, 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9626412/"},{"label":"NICE: QuiremSpheres for unresectable hepatocellular carcinoma","url":"https://www.nice.org.uk/guidance/ta985/chapter/2-Information-about-QuiremSpheres"},{"label":"Safety and efficacy of holmium-166 radioembolization in HCC - the HEPAR Primary study (J Nucl Med, 2022)","url":"https://jnm.snmjournals.org/content/jnumed/early/2022/05/19/jnumed.122.263823.full.pdf"}],"tags":["therapy","beta emitter","gamma emitter","radioembolisation","MRI-visible"],"related":["radioembolisation-tare","y-90","hcc","hcc-intermediate"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"166Ho","element":"Holmium","massNumber":166,"halfLife":"26.8 hours","emissions":["β− 1.77 MeV (48.7%) and 1.85 MeV (50.0%)","γ 81 keV (6.6-6.7%)"],"emissionClass":"beta-minus","use":"both","tissueRange":"Mean about 2.2-2.5 mm, maximum about 8.7-11 mm","production":"Reactor: neutron activation of stable holmium-165 already embedded in the finished PLLA microspheres, 165Ho(n,γ)166Ho.","supply":"adequate","supplyNote":"Single-manufacturer product (Quirem Medical/Terumo) irradiated at specific reactors (e.g. BR2 in Belgium, Maria in Poland); narrower supplier base than 90Y microspheres but not reported as a bottleneck.","chelators":[],"pairedWith":[],"route":"/isotopes/ho-166/"}
{"id":"re-188","kind":"isotope","name":"Rhenium-188","aka":["188Re","Re-188"],"tldr":"A high-energy radioactive metal that a hospital can produce on demand from a small on-site generator, similar to how a common medical imaging isotope is made, rather than needing to import it. It is used for hard-to-reach tumours, including liver cancer.","summary":"Rhenium-188 is a high-energy beta emitter (maximum energies of 2.12 MeV, 71.1% abundance, and 1.96 MeV, 25.6%; mean beta energy around 763-784 keV) with a short 16.9-17.0 hour physical half-life and a co-emitted 155 keV gamma (about 15% abundance) that permits gamma-camera imaging, biodistribution and dosimetry studies -- chemically and logistically analogous to technetium-99m.\n\nIts key practical feature is on-demand generator production: 188Re is eluted as carrier-free sodium perrhenate from a tungsten-188/rhenium-188 generator, in which the long-lived parent 188W (half-life 69.4 days) is fixed on an alumina column, much like a molybdenum-99/technetium-99m generator. A single generator can supply daily eluted doses for around six months to a year, making 188Re one of the few therapeutic isotopes that hospitals in resource-limited settings can access without importing short-lived material.\n\n188W itself is made in a high-flux reactor by double neutron capture on enriched tungsten-186, 186W(n,γ)187W(n,γ)188W, at facilities such as the High Flux Isotope Reactor (Oak Ridge, USA), the SM-3 reactor (Russia) and BR2 (Belgium). 188Re-labelled agents (e.g. 188Re-HDD/lipiodol for hepatocellular carcinoma, 188Re-labelled bone and vascular agents) have been used mainly in investigator-led studies and in India and other countries where the generator route lowers cost, but none has reached FDA or EMA approval.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator (PMC, 2013)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3638650/"},{"label":"Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry (Pharmaceutics, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9921938/"},{"label":"Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications (Front Chem, 2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6587137/"}],"tags":["therapy","beta emitter","gamma emitter","generator-produced"],"related":["hcc","radionuclide-generators-kits","bone-metastases"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"188Re","element":"Rhenium","massNumber":188,"halfLife":"16.9-17.0 hours","emissions":["β− 2.12 MeV maximum (71.1%)","β− 1.96 MeV maximum (25.6%)","γ 155 keV (~15%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Mean about 3.1 mm, maximum about 10-11 mm","production":"Generator: eluted as carrier-free sodium perrhenate from a tungsten-188/rhenium-188 generator; 188W made in a reactor by double neutron capture on enriched 186W, 186W(n,γ)187W(n,γ)188W.","supply":"adequate","supplyNote":"Generator-based, on-demand production keeps 188Re accessible without importing short-lived material; the 69.4-day 188W parent lets one generator supply doses for roughly 6-12 months. 188W production is concentrated at a small number of high-flux reactors (HFIR in the US, SM-3 in Russia, BR2 in Belgium).","chelators":[],"pairedWith":["tc-99m"],"route":"/isotopes/re-188/"}
{"id":"p-32","kind":"isotope","name":"Phosphorus-32","aka":["32P","P-32"],"tldr":"A radioactive form of phosphorus, one of the oldest radioactive treatments in medicine. Because the body's cells constantly use phosphorus, it can be used to treat certain blood disorders or, injected directly into a body cavity, to control fluid build-up caused by cancer.","summary":"Phosphorus-32 decays purely by beta-minus emission (no gamma) with a half-life of 14.27-14.29 days, releasing 1.71 MeV of decay energy with an average beta energy of about 0.695 MeV, to stable sulfur-32. It has no gamma component, so it cannot be imaged with a gamma camera, and is entirely unsuitable for a diagnostic pairing.\n\nAs inorganic sodium phosphate, 32P has been used since 1939 to treat polycythaemia vera and other myeloproliferative disorders, where rapidly dividing marrow cells take up phosphate; as 32P-chromic phosphate colloid, it has been instilled directly into the peritoneal or pleural cavity to palliate malignant ascites or effusions, since colloidal particles are largely retained locally and irradiate the serosal surface. It is one of the oldest therapeutic radionuclides in clinical use and is classified by IARC as carcinogenic to humans (Group 1) based on its therapeutic use.\n\n32P is made in a reactor, most commonly by fast-neutron irradiation of sulfur-32 via the 32S(n,p)32P reaction (chosen because it avoids diluting the product with large amounts of inactive phosphorus), or alternatively by thermal-neutron capture on phosphorus-31, 31P(n,γ)32P. Because of its short half-life it cannot be stockpiled and must be used soon after production, but as a simple, long-established reactor product it is not considered supply-constrained.","status":"approved","asOf":"2026-09-22","links":[{"label":"Phosphorus-32 - isotopic data and properties","url":"https://www.chemlin.org/isotope/phosphorus-32"},{"label":"NCBI: X- and gamma-radiation (phosphorus-32 clinical background)","url":"https://www.ncbi.nlm.nih.gov/books/NBK304365/"},{"label":"PubChem: Phosphorus, radioactive (phosphorus-32 compound summary)","url":"https://pubchem.ncbi.nlm.nih.gov/compound/Phosphorus-Radioisotopes"}],"tags":["therapy","pure beta emitter","historic"],"related":["phosphorus-32","bone-metastases"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"32P","element":"Phosphorus","massNumber":32,"halfLife":"14.27-14.29 days","emissions":["β− average 0.695 MeV, maximum 1.71 MeV (100%, no gamma)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Up to about 8 mm (beta range in tissue)","production":"Reactor: fast-neutron irradiation of sulfur-32, 32S(n,p)32P; or thermal-neutron capture on phosphorus-31, 31P(n,γ)32P.","supply":"adequate","supplyNote":"Simple, long-established reactor product; short half-life means it cannot be stockpiled and must be used soon after irradiation, but production is not considered constrained.","chelators":[],"pairedWith":[],"since":1939,"route":"/isotopes/p-32/"}
{"id":"th-227","kind":"isotope","name":"Thorium-227","aka":["227Th","Th-227"],"tldr":"A radioactive metal that, once it decays, keeps generating more damaging radioactive particles inside the tumour for weeks. Because it lasts longer than most similar treatments, it can be attached to slow-moving carriers such as full-sized antibodies.","summary":"Thorium-227 is an alpha emitter with an 18.7-day half-life -- long enough, unlike most alpha emitters, to be conjugated to slow-clearing targeting molecules such as full antibodies rather than only fast peptides. It decays through a five-alpha cascade (via 223Ra, 219Rn, 215Po, 211Pb, 211Bi, 211Po) to stable 207Tl/207Pb, releasing a total of about 32.4 MeV of alpha energy and roughly 0.96 MeV of beta energy per decay chain, making it an in vivo generator of its own daughter, radium-223.\n\nIt is chelated using octadentate 3,2-hydroxypyridinone (3,2-HOPO) ligands rather than the DOTA-family macrocycles used for most other alpha and beta emitters, and has been developed by Bayer as 'targeted thorium conjugates' (TTCs), including antibody-based constructs such as BAY 2315497 (anti-PSMA) and BAY2701439 (anti-HER2), both tested in early-phase trials.\n\n227Th is obtained from the same generator/supply chain as radium-223: it is the immediate alpha-decay daughter of actinium-227 (itself made by neutron irradiation of radium-226 in a reactor, 226Ra(n,γ)227Ra → β− → 227Ac), separated from the growing 227Ac/227Th/223Ra generator column. Because production piggybacks on the well-established 223Ra supply chain (ORNL, PNNL, Rosatom, Bayer), 227Th is considered available at the research and early-clinical scale, though its co-produced daughter 223Ra must be removed and accounted for as a radioactive impurity in any 227Th-labelled drug product.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Targeted thorium-227 conjugates as treatment options in oncology (Front Med, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9885765/"},{"label":"Production and supply of alpha particle emitting radionuclides for TAT (JNM, 2021)","url":"https://jnm.snmjournals.org/content/jnumed/early/2021/07/22/jnumed.120.261016.full.pdf"},{"label":"Development of radiopharmaceuticals for targeted alpha therapy (PMC, 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9812962/"}],"tags":["therapy","alpha emitter","antibody-compatible","in vivo generator"],"related":["ra-223","targeted-alpha-therapy","her2","psma"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"227Th","element":"Thorium","massNumber":227,"halfLife":"18.7 days","emissions":["α cascade (via 223Ra, 219Rn, 215Po, 211Pb, 211Bi, 211Po) to stable 207Pb: total ~32.4 MeV α, ~0.96 MeV β per chain","γ 236 keV (11.2%) and 50 keV (8.5%)"],"emissionClass":"alpha","use":"therapy","tissueRange":"Tens of micrometres (alpha range), delivered progressively as the daughter chain decays","production":"Generator: harvested from a reactor-derived 227Ac source (226Ra(n,γ)227Ra → β− → 227Ac), from which 227Th is separated on an ongoing basis.","supply":"emerging","supplyNote":"Piggybacks on the 223Ra/227Ac supply chain (ORNL, PNNL, Rosatom, Bayer, and in Europe the Institute for Energy Technology in Norway distributed via Bayer, or JRC Karlsruhe for the PRISMAP consortium); available at research and early-clinical scale but not yet at large commercial scale.","chelators":["3,2-HOPO (octadentate hydroxypyridinone)"],"pairedWith":["zr-89"],"route":"/isotopes/th-227/"}
{"id":"ra-224","kind":"isotope","name":"Radium-224","aka":["224Ra","Ra-224"],"tldr":"A radioactive form of radium used mainly as a feedstock: it is loaded into a small on-site generator so that hospitals and manufacturers can draw off a different, more widely used radioactive metal (lead-212) whenever they need it.","summary":"Radium-224 decays by alpha emission with a half-life of 3.63 days, part of the thorium-232 decay series. Including its full decay chain through radon-220, polonium-216, lead-212, bismuth-212 and either polonium-212 or thallium-208 down to stable lead-208, a single 224Ra decay ultimately yields a cumulative 400% alpha and 200% beta emission (an average alpha energy of about 6.75 MeV per decay in the chain).\n\nIn current practice, 224Ra is used less as a therapeutic agent in its own right than as the loaded parent of a radionuclide generator: it is retained on a cation-exchange or similar column, from which the short-lived gaseous daughter radon-220 emanates and decays to lead-212, which is then eluted for radiolabelling (the DOE's Radium-224/Lead-212/Bismuth-212 generator product). Some experimental 'dual targeting' constructs have also used 224Ra directly, exploiting the fact that three of its four chain alpha particles decay within about 400 micrometres of the original 224Ra atom, while the longer-lived 212Pb daughter can diffuse further before delivering its own alpha dose.\n\n224Ra is obtained from the decay of thorium-228 (half-life about 1.9 years), which is itself recovered from decaying stocks of uranium-232; the DOE Isotope Program has supplied 224Ra/212Pb/212Bi generators (routinely available in batches up to about 16 mCi, ordered 8-10 weeks in advance) since 2015, drawing on thorium-228 separated at Oak Ridge National Laboratory.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"DOE Isotope Program: Radium-224/Lead-212/Bismuth-212 Generator Product Information","url":"https://isotopes.gov/sites/default/files/2024-11/Radium-224-Lead-212-Bismuth-212%20Generator%20Product%20Information%20.pdf"},{"label":"Dual targeting with 224Ra/212Pb-conjugates for cancer therapy (PMC, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9887039/"},{"label":"PRISMAP: 224Ra radionuclide portfolio page","url":"https://www.prismap.eu/radionuclides/portfolio/224Ra/"}],"tags":["therapy","alpha emitter","generator parent","research-only"],"related":["pb-212","targeted-alpha-therapy"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"224Ra","element":"Radium","massNumber":224,"halfLife":"3.63 days","emissions":["α 5.685 and 5.449 MeV (224Ra itself)","full decay chain to stable 208Pb: cumulative 400% α, 200% β− per 224Ra decay"],"emissionClass":"alpha","use":"therapy","tissueRange":"About 400 micrometres for the near-immediate chain alpha particles; longer for the diffusing 212Pb daughter","production":"Decay of parent thorium-228 (itself recovered from decaying uranium-232 stocks); loaded onto generator columns from which 224Ra or its daughter 212Pb can be eluted.","supply":"research-only","supplyNote":"Supplied by the DOE Isotope Program as 224Ra/212Pb/212Bi generators (batches up to about 16 mCi, order lead time 8-10 weeks), sourced from thorium-228 separated from decaying uranium-232 stocks at Oak Ridge National Laboratory.","chelators":[],"pairedWith":[],"route":"/isotopes/ra-224/"}
{"id":"sc-47","kind":"isotope","name":"Scandium-47","aka":["47Sc","Sc-47"],"tldr":"A radioactive metal being developed to pair with imaging twins made of the same element, scandium-43 or scandium-44. Because it is the same chemical element used for both the scan and the treatment, the tracer should behave identically in both roles.","summary":"Scandium-47 decays by beta-minus emission with a half-life of about 3.35 days to stable titanium-47, releasing beta particles with a mean energy around 162 keV (maxima cited between about 440-600 keV depending on the source) and an imageable 159 keV gamma (about 68% abundance), giving a mean tissue range broadly comparable to lutetium-177.\n\nIts intended theranostic partners are the positron emitters scandium-43 (half-life 3.89 hours) and scandium-44 (half-life about 4.04 hours), which would let the same chelator-conjugated ligand be imaged by PET and then dosed with 47Sc using identical chemistry -- an isotopic match analogous to the 64Cu/67Cu copper pair, though scandium's shorter-lived PET isotopes make routine same-day imaging-then-therapy workflows more logistically demanding.\n\n47Sc can be produced in a reactor either directly by fast-neutron irradiation of enriched titanium-47, 47Ti(n,p)47Sc, or indirectly via thermal-neutron capture on enriched calcium-46 to form calcium-47 (half-life 4.54 days), which beta-decays to 47Sc and can also serve as a 47Ca/47Sc generator; it can also be made in a cyclotron by proton irradiation of titanium-48, 48Ti(p,2n)47Sc, though this route has shown lower radionuclidic purity due to co-produced scandium-46 and -48. Production remains at research-reactor and pilot scale (for example, the PRISMAP network's ILL, SCK CEN and NCBJ reactors), and 47Sc-labelled radiopharmaceuticals are in early preclinical and clinical development, not yet FDA- or EMA-approved.","status":"preclinical","asOf":"2026-09-22","links":[{"label":"Production of scandium radionuclides for theranostic applications (EJNMMI Radiopharm Chem, 2021)","url":"https://link.springer.com/article/10.1186/s41181-021-00131-2"},{"label":"47Sc as useful beta-minus-emitter for the radiotheragnostic paradigm (PMC, 2017)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5824697/"},{"label":"Production and purification of 43Sc and 47Sc from enriched titanium targets (Sci Rep, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10730517/"},{"label":"PRISMAP: 47Sc radionuclide portfolio page","url":"https://www.prismap.eu/radionuclides/portfolio/47Sc/"}],"tags":["therapy","beta emitter","gamma emitter","research-only","theranostic pair"],"related":["lu-177","prrt"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"47Sc","element":"Scandium","massNumber":47,"halfLife":"3.35 days","emissions":["β− mean 162 keV","γ 159 keV (~68%)"],"emissionClass":"beta-minus","use":"therapy","tissueRange":"Comparable to 177Lu (sub-millimetre to low-millimetre beta range)","production":"Reactor: thermal-neutron capture on enriched calcium-46, 46Ca(n,γ)47Ca (t1/2 4.54 d) → β− → 47Sc; or fast-neutron irradiation of enriched titanium-47, 47Ti(n,p)47Sc. Also cyclotron 48Ti(p,2n)47Sc.","supply":"research-only","supplyNote":"Produced at research-reactor, gigabecquerel/pilot scale (e.g. PRISMAP network reactors ILL, SCK CEN, NCBJ); not yet available at routine clinical-supply scale.","chelators":["DOTA","DOTATOC/DOTATATE-type macrocycles"],"pairedWith":["ga-68"],"route":"/isotopes/sc-47/"}
{"id":"pluvicto-plus-olaparib","kind":"pairing","name":"177Lu-PSMA-617 (Pluvicto) with olaparib","aka":[],"tldr":"An early trial gave the prostate cancer radiotherapy Pluvicto together with the tablet olaparib, on the idea that the pill makes the radiation harder for the cancer cell to repair. Most men's PSA fell, but this is still a small early-stage study, not proof it helps people live longer.","summary":"LuPARP (NCT03874884) is a phase 1 dose-escalation and dose-expansion trial run by Sandhu, Joshua, Emmett and colleagues (Peter MacCallum Cancer Centre and collaborators) combining 177Lu-PSMA-617 (7.4 GBq every 6 weeks, up to 6 cycles) with olaparib at doses from 50 mg to 300 mg twice daily, given on varying schedules relative to the radioligand infusion. The rationale is mechanistic: 177Lu-PSMA-617 causes single-strand DNA breaks that are normally repaired through PARP-dependent base-excision repair, and PARP inhibition is intended to convert these into lethal double-strand breaks, radiosensitising the tumour irrespective of BRCA or other homologous-recombination-repair status.\n\nAcross the 48 enrolled patients with mCRPC previously treated with an androgen-receptor pathway inhibitor and docetaxel, no dose-limiting toxicities were reported and the recommended phase 2 dose was set at olaparib 300 mg twice daily on days -4 to 18 of each 6-week cycle. In the overall cohort, the PSA50 response rate was 66% and PSA90 was 44%, with an objective response rate of 78% by RECIST v1.1 (comparable to, and in the PSA90 measure slightly higher than, the single-agent benchmarks from TheraP and VISION). Hematologic grade 3 toxicity was low (anaemia, neutropenia and thrombocytopenia each in the single digits of percent) and no patient discontinued for toxicity.\n\nThis is dose-finding, single-arm evidence in a heavily pre-treated population, not a randomised comparison, so it cannot show whether adding olaparib improves survival or response over 177Lu-PSMA-617 alone; a randomised phase 2 component was being planned as of the 2023 report. Trials of 225Ac-PSMA-I&T plus olaparib (e.g. NCT06909825) are testing the same radiosensitisation idea with an alpha emitter.","asOf":"2026-09-22","links":[{"label":"LuPARP phase 1 abstract (Sandhu et al., ASCO 2023, J Clin Oncol 41:5005)","url":"https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5005"},{"label":"UroToday conference summary of LuPARP results and comparison with TheraP/VISION","url":"https://www.urotoday.com/conference-highlights/asco-2023/asco-2023-prostate-cancer/144916-asco-2023-luparp-phase-1-trial-of-177lu-psma-617-and-olaparib-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc.html"},{"label":"ClinicalTrials.gov: NCT03874884 (LuPARP)","url":"https://clinicaltrials.gov/study/NCT03874884"}],"tags":["prostate cancer","PARP inhibitor","early phase"],"related":["prostate-mcrpc","parp","radionuclide-parp-combination","sandhu-shahneen","louise-emmett","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"pluvicto","b":"olaparib","rationale":"177Lu-PSMA-617 causes single-strand DNA breaks that are normally repaired through PARP-dependent base-excision repair; adding a PARP inhibitor is intended to convert these into lethal double-strand breaks and radiosensitise the tumour.","evidence":"LuPARP phase 1 trial (NCT03874884, n=48 mCRPC): no dose-limiting toxicities, recommended phase 2 dose olaparib 300 mg BD days -4 to 18; PSA50 66%, PSA90 44%, RECIST objective response rate 78% (Sandhu et al., ASCO 2023).","pairingType":"combination","route":"/pairings/pluvicto-plus-olaparib/"}
{"id":"prrt-plus-captem","kind":"pairing","name":"PRRT (177Lu-DOTATATE) with capecitabine and temozolomide (CAPTEM)","aka":[],"tldr":"For some pancreatic neuroendocrine tumours, doctors add two chemotherapy tablets (capecitabine and temozolomide) to the radioactive PRRT treatment. Trial data suggest the combination may control the pancreatic tumours for longer than either treatment alone, though it caused more blood-count side effects in one gut-tumour subgroup.","summary":"The Australasian Gastrointestinal Trials Group CONTROL NET study (Pavlakis et al.) is a randomised, open-label phase 2 trial that tested 177Lu-octreotate PRRT combined with capecitabine plus temozolomide (CAPTEM) against PRRT alone (midgut NET cohort) or CAPTEM alone (pancreatic NET, pNET, cohort). Chemoradionuclide therapy is given on the premise that temozolomide's DNA-alkylating damage is potentiated by concurrent radiation, an approach analogous to the CAPTEM regimen already used as chemotherapy alone in NETs.\n\nIn the pNET cohort, PRRT/CAPTEM produced a numerically longer median progression-free survival (not reached versus 14 months for CAPTEM alone) and a higher objective response rate (44% versus 28%, and in an earlier interim readout 67% versus 33%). In the midgut NET cohort the two regimens performed similarly on the 15-month progression-free survival endpoint (90% for PRRT/CAPTEM versus 92% for PRRT alone), with a numerically higher objective response rate for the combination (31-34% versus 15-23%) but at the cost of roughly double the grade 3/4 haematological toxicity (88% versus 46%).\n\nThe trial's own conclusion is that CAPTEM/PRRT activity in pNETs is durable enough to justify phase 3 testing, while in midgut NETs the extra toxicity did not appear matched by extra benefit. This is consistent with a wider literature (systematic review, PMC9790144) reporting CAPTEM alone achieves roughly 77% disease control across NET subtypes, most convincingly in pancreatic disease, and with retrospective comparisons finding broadly similar progression-free survival between PRRT and CAPTEM given sequentially rather than together.","asOf":"2026-09-22","links":[{"label":"AGITG CONTROL NET final results (Pavlakis et al., ASCO 2022, J Clin Oncol 40:4122)","url":"https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4122"},{"label":"AGITG CONTROL NET midgut NET first results (ASCO 2020, J Clin Oncol 38:604)","url":"https://ascopubs.org/doi/10.1200/JCO.2020.38.4_suppl.604"},{"label":"JONS-online summary of CONTROL NET pancreatic and midgut results","url":"https://www.jons-online.com/special-issues-and-supplements/2020/2020-year-in-review-neuroendocrine-tumors/177lu-octreotate-prrt-temozolomide-capecitabine-in-pancreas-and-updated-midgut-nets"},{"label":"Systematic review of CAPTEM in advanced NENs (PMC9790144)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9790144/"}],"tags":["neuroendocrine tumours","chemoradionuclide therapy"],"related":["pancreatic-net","neuroendocrine","temozolomide","prrt","jonathan-strosberg","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"lutathera","b":"capecitabine","rationale":"Temozolomide's DNA-alkylating damage is thought to be potentiated by concurrent radiation from PRRT, so combining CAPTEM chemotherapy with PRRT ('chemoradionuclide therapy') may increase response over either given alone.","evidence":"AGITG CONTROL NET randomised phase 2 trial: in pancreatic NETs, PRRT/CAPTEM had a higher objective response rate than CAPTEM alone (44% vs 28%) and longer median PFS (not reached vs 14 months); in midgut NETs, 15-month PFS was similar (90% vs 92%) but grade 3/4 toxicity was roughly doubled with the combination (Pavlakis et al., ASCO 2022).","pairingType":"combination","route":"/pairings/prrt-plus-captem/"}
{"id":"radium223-abiraterone-caution","kind":"pairing","name":"Radium-223 with abiraterone: a caution, not a combination","aka":[],"tldr":"Giving the bone-targeting radiotherapy radium-223 together with the hormone drug abiraterone does not help patients live longer and roughly doubles or triples the risk of a broken bone compared with abiraterone alone. This combination is no longer recommended.","summary":"ERA-223 was a randomised, double-blind, placebo-controlled phase 3 trial (Smith et al., sponsored by Bayer) in 806 men with asymptomatic or mildly symptomatic bone-predominant metastatic castration-resistant prostate cancer, comparing radium-223 plus abiraterone acetate/prednisone/prednisolone against placebo plus abiraterone acetate/prednisone/prednisolone. The trial was unblinded prematurely on 17 November 2017, before completion of follow-up, after an unplanned ad hoc analysis showed more fractures and more deaths in the radium-223 arm.\n\nAt the primary analysis (data cut-off 15 February 2018), the combination did not improve the primary endpoint of symptomatic skeletal-event-free survival: median 22.3 months with radium-223 versus 26.0 months with placebo (hazard ratio 1.122, 95% CI 0.917-1.374, p=0.26). Overall survival was numerically shorter with radium-223 (30.7 versus 33.3 months; 155 deaths [39%] versus 141 deaths [35%]) though the difference was not statistically significant. The starkest signal was fracture risk: any-grade fractures occurred in 29% of the radium-223 group versus 11% of the placebo group in the extended follow-up analysis (26% versus 10% during the on-treatment period). Independent central review confirmed 76 patients with at least one fracture in the combination arm versus 23 on placebo, with osteoporotic (fragility) fractures nearly tenfold more common (37 versus 4 patients). Fracture risk was substantially reduced, but not eliminated, by concurrent bone-health agents (bisphosphonates or denosumab): 15% versus 7% fracture incidence with and without radium-223 among bone-health-agent users, compared with much higher rates in patients not on a bone-health agent.\n\nOn the basis of ERA-223, the investigators explicitly do not recommend radium-223 in combination with abiraterone acetate plus prednisone/prednisolone, and the FDA and EMA revised prescribing information for radium-223 accordingly. This is one of the clearest examples in prostate-cancer radiopharmaceutical practice where two active, individually beneficial agents (radium-223 improved overall survival in ALSYMPCA; abiraterone improves survival in mCRPC) produce net harm when combined, and it is now standard teaching to avoid concurrent radium-223 and abiraterone outside a bone-health-agent-protected, closely monitored context.","asOf":"2026-09-22","links":[{"label":"Smith et al., ERA-223 primary results, Lancet Oncology 2019 (open-access PDF via UCLouvain)","url":"https://dial.uclouvain.be/pr/boreal/object/boreal:213463/datastream/PDF_02/view"},{"label":"ASCO Post summary of ERA-223 (fracture rate, OS)","url":"https://ascopost.com/issues/november-25-2018/treatment-with-radium-223-plus-abiraterone-not-advisable-in-metastatic-prostate-cancer/"},{"label":"PMC review discussing ERA-223 unblinding and fracture subtypes","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6642951/"}],"tags":["prostate cancer","safety signal","fractures"],"related":["prostate-mcrpc","bone-metastases","chris-parker","karim-fizazi","arpi","ra-223"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"radium-223","b":"abiraterone","rationale":"Both agents are individually beneficial in mCRPC (radium-223 improves survival in ALSYMPCA, abiraterone improves survival in mCRPC), so combining a bone-seeking alpha emitter with an androgen-receptor pathway inhibitor was hypothesised to add benefit; the trial testing this was stopped early for harm.","evidence":"ERA-223 phase 3 trial (n=806) was unblinded prematurely after excess fractures and deaths in the radium-223 arm: fractures occurred in 29% vs 11% of patients (radium-223 vs placebo, both plus abiraterone/prednisone), symptomatic skeletal-event-free survival was not improved (22.3 vs 26.0 months, HR 1.122, p=0.26), and overall survival was numerically shorter (30.7 vs 33.3 months) (Smith et al., Lancet Oncology 2019).","pairingType":"caution","route":"/pairings/radium223-abiraterone-caution/"}
{"id":"fdg-pet-response-adapted-therapy","kind":"pairing","name":"FDG PET then response-adapted chemotherapy","aka":[],"tldr":"In Hodgkin lymphoma, a PET scan taken partway through chemotherapy is used to decide whether to keep the same treatment, drop a harsh drug, or step up to something stronger. Trials show this scan-guided approach keeps most patients well without adding one particular lung-damaging drug.","summary":"RATHL (Response-Adapted Therapy in advanced Hodgkin Lymphoma; NCT00678327; Johnson et al., NEJM 2016) enrolled 1214 patients (1119 evaluable) with stage IIB-IV or bulky IIA classical Hodgkin lymphoma. All patients received two cycles of ABVD chemotherapy and then an interim FDG PET-CT scan (PET2). Patients with a negative PET2 (Deauville score 1-3; 83.7% of scanned patients) were randomised to continue ABVD or to drop bleomycin (AVD) for the remaining four cycles; those with a positive PET2 were escalated to BEACOPP-14 or escalated BEACOPP, with no randomisation in that arm.\n\nAt a median follow-up of 41 months, 3-year progression-free survival in PET2-negative patients was 85.7% with continued ABVD versus 84.4% with AVD (absolute difference 1.6 percentage points, within the prespecified non-inferiority margin), while overall survival was around 97% in both arms; the trial's practical conclusion was that bleomycin can be safely omitted after a negative interim scan, reducing pulmonary toxicity with an estimated treatment-failure risk of only 1.6%. PET2-positive patients who were escalated to BEACOPP reached a 3-year progression-free survival of 67.5%, which the investigators judged better than historical rates of continuing ABVD alone in PET2-positive disease (previously reported in the 15-45% range). Long-term follow-up (Blood 2022; JCO 2024) confirmed durability of both the de-escalation and escalation strategies.\n\nRATHL is the paradigm case for FDG-PET-guided, response-adapted treatment and sits alongside other PET2-adapted trials (Italian GITIL/FIL HD0607, US Intergroup S0816) that validated the same principle: interim FDG-PET response predicts outcome and can be used prospectively to tailor chemotherapy intensity. The same logic (imaging mid-treatment to decide whether to change systemic therapy) generalises to other FDG-avid cancers, for example the germ-cell tumour and lymphoma literature more broadly, though the specific numbers above are for classical Hodgkin lymphoma.","asOf":"2026-09-22","links":[{"label":"Johnson P, et al. RATHL: adapted treatment guided by interim PET-CT, N Engl J Med 2016;374:2419-2429","url":"https://thd.org.tr/thdData/userfiles/file/RATHL_Adapted_Treatment_Guided_by_Interim_PET-CT_Scan-2016_NEJM.pdf"},{"label":"PMC review of PET-adapted approaches to primary therapy for advanced Hodgkin lymphoma","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7268111/"},{"label":"Long-term follow-up of RATHL (Luminari et al., J Clin Oncol 2024)","url":"https://ascopubs.org/doi/10.1200/JCO.23.01177"}],"tags":["Hodgkin lymphoma","response-adapted therapy","FDG PET"],"related":["rathl","paper-rathl-interim-pet-adapted-abvd-advanced-hodgkin-nejm-2016","quantitative-imaging-biomarkers","pierre-vera"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"fdg-pet","b":"pet-adapted-therapy","rationale":"FDG uptake after two cycles of chemotherapy predicts long-term outcome in Hodgkin lymphoma, so an interim scan can be used prospectively to de-escalate treatment for good responders (reducing toxicity) or escalate it for poor responders (improving control).","evidence":"RATHL (n=1214, NCT00678327): in interim-PET-negative patients, 3-year progression-free survival was 85.7% with continued ABVD vs 84.4% after dropping bleomycin (AVD), supporting safe de-escalation; interim-PET-positive patients escalated to BEACOPP reached 67.5% 3-year progression-free survival, better than historical rates with unmodified ABVD (Johnson et al., NEJM 2016).","pairingType":"platform","route":"/pairings/fdg-pet-response-adapted-therapy/"}
{"id":"tare-plus-durvalumab-hcc","kind":"pairing","name":"Radioembolisation (TARE) with durvalumab in hepatocellular carcinoma","aka":[],"tldr":"Small early trials are giving liver-directed radiation beads (TARE) together with the immunotherapy drug durvalumab for liver cancer that cannot be operated on. Early results show high tumour shrinkage rates, but these are small studies and it is not yet proven that the combination helps people live longer than either treatment alone.","summary":"A phase I/IIa pilot trial (Aliseda et al., Clinical Cancer Research 2023) treated 24 patients with locally advanced, unresectable hepatocellular carcinoma (Child-Pugh score up to 7, BCLC stage B or non-metastatic BCLC-C) with yttrium-90 radioembolisation followed 7-14 days later by intravenous durvalumab 1500 mg every 4 weeks. At a median follow-up of 19 months, median time to progression was 15.2 months, 18-month overall survival was 58.3%, and the objective response rate by modified RECIST was 83.3% (29.2% complete response, 54.2% partial response). Toxicity was modest: 47.8% of patients had any-grade treatment-related adverse events and only 8.7% had grade 3 events (neutropenia, fever), with no treatment-related serious adverse events.\n\nThis single-arm signal has prompted larger prospective studies of TARE plus durvalumab-based regimens, including the phase II ROWAN study (NCT05063565, Boston Scientific-sponsored, TheraSphere followed by durvalumab plus a single dose of tremelimumab, the STRIDE regimen; enrolment of 100 patients completed August 2025, results expected 2027) and EMERALD-Y90 (NCT06040099, AstraZeneca-sponsored, TARE followed by durvalumab and bevacizumab, 58 patients enrolled). A retrospective National Cancer Database analysis of 1,664 patients cited by Boston Scientific also associated TARE plus immunotherapy with improved survival compared with immunotherapy alone, though retrospective comparisons of this kind cannot rule out selection bias.\n\nAs of September 2026 none of the randomised, adequately powered trials of TARE plus systemic immunotherapy in HCC has reported a definitive survival readout; the evidence base is early-phase and registry-level. Clinicians should treat the high response rates from the pilot study as hypothesis-generating rather than practice-changing pending ROWAN and EMERALD-Y90 results.","asOf":"2026-09-22","links":[{"label":"Aliseda et al., Y90-radioembolisation plus durvalumab phase I/IIa trial, Clin Cancer Res 2023;29:3650-3658","url":"https://pubmed.ncbi.nlm.nih.gov/37459133/"},{"label":"Boston Scientific TheraSphere systemic therapy combination evidence brochure","url":"https://www.bostonscientific.com/content/dam/bsc/us/pi/ir/ioe/therasphere/downloads/TheraSphere-Systemic-Brochure.pdf"},{"label":"ROWAN study (NCT05063565) enrolment-complete summary","url":"https://oncodaily.com/oncolibrary/immune-oncology/rowan-study-enrol-complet"},{"label":"ClinicalTrials.gov: NCT06040099 (EMERALD-Y90, TARE + durvalumab + bevacizumab)","url":"https://clinicaltrials.gov/study/NCT06040099"}],"tags":["hepatocellular carcinoma","radioembolisation","immunotherapy"],"related":["hcc","sirtex","boston-scientific","astrazeneca","nct05063565","nct06040099","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"radioembolisation-tare","b":"durvalumab","rationale":"Radiation from TARE can release tumour antigens and prime an immune response, providing a rationale for combining it with checkpoint blockade in unresectable hepatocellular carcinoma where systemic options are limited.","evidence":"Phase I/IIa pilot trial (n=24): objective response rate 83.3% by modified RECIST (29.2% complete response), 18-month overall survival 58.3%, low grade 3 toxicity (8.7%) (Aliseda et al., Clin Cancer Res 2023); larger randomised readouts (ROWAN, NCT05063565; EMERALD-Y90, NCT06040099) are pending as of September 2026.","pairingType":"combination","route":"/pairings/tare-plus-durvalumab-hcc/"}
{"id":"tare-vs-sorafenib-caution","kind":"pairing","name":"Radioembolisation (TARE) compared with sorafenib in hepatocellular carcinoma","aka":[],"tldr":"Two large trials tested whether liver-directed radiation beads work better than the pill sorafenib for advanced liver cancer. Neither trial found the radiation beads extended life more than the pill, though patients had fewer side effects and better quality of life with the beads.","summary":"SARAH (SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma; NCT01482442; Vilgrain et al., Lancet Oncology 2017) and SIRveNIB (SIRT versus sorafenib; NCT01135056; Chow et al., JCO 2018) were both open-label, randomised phase 3 trials designed to show superiority of yttrium-90 resin-microsphere radioembolisation (TARE/SIRT) over sorafenib 800 mg/day in locally advanced, unresectable hepatocellular carcinoma, with overall survival as the primary endpoint.\n\nSARAH randomised 467 patients (237 TARE, 222 sorafenib) across 25 French centres; median overall survival was 8.0 months with TARE versus 9.9 months with sorafenib (hazard ratio 1.15, 95% CI 0.94-1.41, p=0.18) — numerically worse, not better, with TARE, and the trial did not meet its superiority endpoint. SIRveNIB randomised 360 patients (182 TARE, 178 sorafenib) across 11 Asia-Pacific countries; median overall survival was 8.8 months with TARE versus 10.0 months with sorafenib (hazard ratio 1.1, 95% CI 0.9-1.4, p=0.36), again not meeting its superiority endpoint. In both trials tumour response rates were numerically higher with TARE, and grade 3 or worse adverse events and serious adverse events were significantly less frequent with TARE than with sorafenib (in SIRveNIB, grade ≥3 events in 27.7% versus 50.6% of treated patients).\n\nThe consistent message from both randomised trials is that TARE has not been shown to extend survival beyond sorafenib in this population, despite earlier retrospective and registry data suggesting a survival advantage for radioembolisation; the 2018 EASL practice guidelines subsequently did not recommend radioembolisation as a substitute for sorafenib in this setting. TARE's better tolerability and quality-of-life profile may still inform treatment choice for individual patients, but this is a caution against assuming imaging-guided intra-arterial radiotherapy is simply a 'better' alternative to systemic therapy on survival grounds alone.","asOf":"2026-09-22","links":[{"label":"Vilgrain et al., SARAH trial primary results, Lancet Oncol 2017 (PubMed)","url":"https://pubmed.ncbi.nlm.nih.gov/29107679/"},{"label":"Chow et al., SIRveNIB trial primary results, J Clin Oncol 2018 (PubMed)","url":"https://pubmed.ncbi.nlm.nih.gov/29498924/"},{"label":"PMC review comparing SARAH and SIRveNIB outcomes","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6295389/"}],"tags":["hepatocellular carcinoma","radioembolisation","negative trial"],"related":["hcc-intermediate","hcc","sarah-sirvenib","sirtex","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"radioembolisation-tare","b":"sorafenib","rationale":"Retrospective and registry data had suggested radioembolisation might match or beat sorafenib's survival benefit with a better safety profile, prompting two head-to-head randomised phase 3 trials designed to show TARE's superiority.","evidence":"SARAH (n=467): median overall survival 8.0 months (TARE) vs 9.9 months (sorafenib), HR 1.15, p=0.18. SIRveNIB (n=360): 8.8 vs 10.0 months, HR 1.1, p=0.36. Neither trial met its superiority endpoint, though grade ≥3 adverse events were less frequent with TARE (Vilgrain et al., Lancet Oncol 2017; Chow et al., JCO 2018).","pairingType":"caution","route":"/pairings/tare-vs-sorafenib-caution/"}
{"id":"rituximab-then-ibritumomab-tiuxetan","kind":"pairing","name":"Rituximab pretreatment before ibritumomab tiuxetan (Zevalin)","aka":[],"tldr":"Before giving the radioactive lymphoma treatment Zevalin, doctors first give a dose of the antibody drug rituximab. This clears out normal B-cells in the blood so the radioactivity goes to the lymphoma more precisely, and it is a mandatory step on the drug's official label, not an optional extra.","summary":"Ibritumomab tiuxetan (Zevalin), a yttrium-90-labelled anti-CD20 radioimmunotherapy, is administered only as part of a fixed two-step regimen defined in its FDA label and EMA product information. On day 1, patients receive rituximab 250 mg/m2 by intravenous infusion; seven to nine days later, a second rituximab infusion (250 mg/m2) is given, followed within four hours by the therapeutic yttrium-90 ibritumomab tiuxetan infusion, dosed at 0.4 mCi/kg (14.8 MBq/kg) for patients with platelet counts of 150,000/mm3 or more, or a reduced 0.3 mCi/kg (11.1 MBq/kg) for platelet counts of 100,000-149,000/mm3, with a maximum activity cap of 32 mCi regardless of body weight.\n\nThe pharmacological rationale, stated explicitly in the EMA summary of product characteristics, is that rituximab pretreatment clears circulating and marginal-zone CD20-positive B-cells, which would otherwise act as a radioactivity 'sink' and reduce the fraction of the yttrium-90 dose reaching lymphoma cells; the rituximab dose used in the Zevalin regimen is deliberately lower than the dose used when rituximab is given as monotherapy. Zevalin is approved for relapsed or refractory low-grade or follicular B-cell non-Hodgkin lymphoma, and as consolidation after first-line induction chemotherapy in previously untreated follicular lymphoma (the latter still requiring the same rituximab-then-Zevalin sequence).\n\nBecause rituximab must be ordered and administered separately from the Zevalin kit, this is one of the clearest examples of a mandated, label-level drug sequence in radiopharmaceutical practice: Zevalin cannot be lawfully administered without preceding rituximab, and the labels carry boxed warnings for infusion reactions (during the rituximab step) and for prolonged, severe cytopenias following the radiolabelled step.","asOf":"2026-09-22","links":[{"label":"FDA label: Zevalin (ibritumomab tiuxetan), 2018 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125019s227lbl.pdf"},{"label":"EMA product information: Zevalin (rituximab pretreatment rationale and dosing)","url":"https://ec.europa.eu/health/documents/community-register/2020/20200211147169/anx_147169_en.pdf"}],"tags":["lymphoma","radioimmunotherapy","mandatory sequence"],"related":["cd20","dlbcl","follicular-lymphoma","radioimmunotherapy","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"rituximab","b":"ibritumomab-tiuxetan","rationale":"Rituximab pretreatment clears circulating and marginal-zone CD20-positive B-cells that would otherwise compete for binding, so the radiolabelled antibody given afterwards delivers more of its radiation dose specifically to lymphoma cells.","evidence":"The FDA label and EMA SmPC for Zevalin mandate a fixed two-step regimen: rituximab 250 mg/m2 on day 1, then a second rituximab 250 mg/m2 infusion on day 7-9 followed within 4 hours by yttrium-90 ibritumomab tiuxetan at 0.4 mCi/kg (or 0.3 mCi/kg if platelets 100,000-149,000/mm3), capped at 32 mCi total.","pairingType":"sequence","route":"/pairings/rituximab-then-ibritumomab-tiuxetan/"}
{"id":"beta-psma-then-alpha-psma-rescue","kind":"pairing","name":"177Lu-PSMA-617 then 225Ac-PSMA rescue therapy","aka":[],"tldr":"When the standard radioactive prostate cancer treatment (177Lu-PSMA) stops working, some clinics switch to a more powerful alpha-particle version (225Ac-PSMA) as a rescue option. It can bring PSA down in about half of patients, but people who have already failed the beta treatment tend to respond less well and for a shorter time than those who have never had it.","summary":"225Ac-PSMA-617 or 225Ac-PSMA-I&T alpha-particle radioligand therapy is used, mainly outside the United States where actinium-225 is more accessible (for example in Germany), as salvage treatment for metastatic castration-resistant prostate cancer that has progressed after beta-emitting 177Lu-PSMA radioligand therapy (such as Pluvicto) plus prior androgen-receptor pathway inhibitors and taxane chemotherapy. Zacherl et al. (J Nucl Med 2021) reported the first dedicated series: of 14 patients treated with 225Ac-PSMA-I&T, 11 (79%) had previously received 177Lu-PSMA; 50% achieved a PSA decline of 50% or more, with median progression-free survival of 3.1 months and median overall survival of 7.7 months.\n\nA subsequent meta-analysis of retrospective 225Ac-PSMA-617 series (largely post-177Lu-PSMA patients) found pooled rates of 87% for any PSA decline and 66% for a PSA50 response, with pooled median overall survival of 12.5 months and progression-free survival of 9.1 months, and a molecular imaging response in 54% of patients — activity that the authors describe as clinically meaningful in a population that has exhausted other options, achieved with relatively low toxicity (xerostomia is the dominant, often dose-limiting, side effect; haematological toxicity is generally milder than with 177Lu-PSMA). A larger, more recent single-centre series (2025) similarly reported a median overall survival around 7 months in a mixed population, ranging up to 39 months in favourable cases.\n\nImportantly, multiple groups note that patients who progressed on 177Lu-PSMA before starting 225Ac-PSMA have inferior outcomes compared with alpha-therapy-naive patients (a 2022 series found a 45% versus 50% PSA50 rate, and a 2021 Ezziddin group series used 225Ac-PSMA as an 'augmentation' added to, rather than purely after, 177Lu-PSMA cycles, reporting median PSA-progression-free survival of 9.1 months and overall survival of 14.8 months). 225Ac-PSMA remains investigational (not FDA- or EMA-approved) and randomised trials comparing it against other post-177Lu-PSMA options are still needed; it is generally reserved for salvage use in patients with adequate marrow reserve who have exhausted approved options.","asOf":"2026-09-22","links":[{"label":"Zacherl et al., first clinical results for 225Ac-PSMA-I&T in advanced mCRPC, J Nucl Med 2021;62:669-674","url":"https://jnm.snmjournals.org/content/64/10/1574"},{"label":"Meta-analysis of efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy (PMC8852230)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8852230/"},{"label":"Long-term safety and survival outcomes of 225Ac-PSMA (PMC11816130, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11816130/"}],"tags":["prostate cancer","alpha therapy","salvage therapy"],"related":["prostate-mcrpc","targeted-alpha-therapy","psma","clemens-kratochwil","uwe-haberkorn","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"pluvicto","b":"ac225-psma","rationale":"Alpha particles deposit far more energy per track than beta particles and can still kill tumour cells that have become less responsive to 177Lu-PSMA, making 225Ac-PSMA a mechanistically plausible salvage option after beta-emitter progression.","evidence":"In a series of 14 patients (79% previously treated with 177Lu-PSMA), 225Ac-PSMA-I&T produced a PSA50 response in 50%, with median progression-free survival 3.1 months and overall survival 7.7 months (Zacherl et al., J Nucl Med 2021); a pooled meta-analysis of mostly post-177Lu-PSMA series found 66% PSA50 response and 12.5-month median overall survival, but response is consistently inferior to alpha-therapy-naive patients.","pairingType":"sequence","route":"/pairings/beta-psma-then-alpha-psma-rescue/"}
{"id":"docetaxel-then-lu177-psma","kind":"pairing","name":"Docetaxel (taxane chemotherapy) then 177Lu-PSMA-617","aka":[],"tldr":"In the trial that got 177Lu-PSMA-617 (Pluvicto) approved, everyone had already been treated with a taxane chemotherapy drug like docetaxel and with a hormone pill first. That is the treatment order the approval is based on, though a newer trial is now testing whether Pluvicto can be used earlier, before chemotherapy.","summary":"The pivotal VISION trial (NCT03511664; Sartor et al., NEJM 2021) that supported FDA and EMA approval of 177Lu-PSMA-617 (Pluvicto) enrolled adults with metastatic castration-resistant prostate cancer who had already progressed on at least one androgen-receptor pathway inhibitor (for example abiraterone or enzalutamide) and on one or two prior taxane-based chemotherapy regimens, typically docetaxel. Patients also had to have PSMA-positive disease on centrally read 68Ga-PSMA-11 PET-CT, with no qualifying PSMA-negative lesions. 177Lu-PSMA-617 (7.4 GBq every 6 weeks, up to 6 cycles) plus protocol-permitted standard care was compared with standard care alone; median overall survival was 15.3 months versus 11.3 months (hazard ratio 0.62, 95% CI 0.52-0.74, p<0.001).\n\nBecause prior taxane exposure was a trial entry requirement rather than a randomised comparison of sequencing strategies, VISION establishes an evidence-based treatment order — androgen-receptor pathway inhibitor, then taxane chemotherapy (commonly docetaxel), then 177Lu-PSMA-617 — rather than proving that giving the radioligand therapy after docetaxel is better than giving it before. Retrospective subgroup analyses of VISION found that survival benefit from 177Lu-PSMA-617 was preserved regardless of whether patients had received one or two prior taxane regimens, and regardless of the number of prior androgen-receptor pathway inhibitors.\n\nThis sequencing question is now being tested directly: the phase 3 PSMAfore trial (NCT04689828) enrolled taxane-naive patients progressing after one androgen-receptor pathway inhibitor and randomised them to 177Lu-PSMA-617 or to switching to a different androgen-receptor pathway inhibitor, explicitly to establish whether radioligand therapy can move earlier in the treatment sequence, ahead of chemotherapy, rather than only being used after it.","asOf":"2026-09-22","links":[{"label":"Sartor et al., VISION primary results, N Engl J Med 2021 (full text)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"},{"label":"JNM commentary on VISION eligibility criteria (prior taxane and ARPI requirements)","url":"https://jnm.snmjournals.org/content/63/6/823"},{"label":"PSMAfore design (taxane-naive, ARPI-progressed population), ASCO 2022","url":"https://ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.TPS211"}],"tags":["prostate cancer","treatment sequencing","radioligand therapy"],"related":["prostate-mcrpc","vision","psmafore","paper-vision-nejm-2021","michael-morris","oliver-sartor","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"docetaxel","b":"pluvicto","rationale":"The approval of 177Lu-PSMA-617 rests on a trial population defined by prior treatment order (hormone therapy, then taxane chemotherapy, then radioligand therapy), so this is the evidence-based sequence rather than a proven optimal one.","evidence":"VISION (n=831) required progression after at least one androgen-receptor pathway inhibitor and one or two taxane regimens (typically docetaxel) before enrolment; median overall survival with added 177Lu-PSMA-617 was 15.3 vs 11.3 months (HR 0.62, p<0.001) (Sartor et al., NEJM 2021). PSMAfore (NCT04689828) is testing whether the radioligand therapy can instead be used before taxane chemotherapy.","pairingType":"sequence","route":"/pairings/docetaxel-then-lu177-psma/"}
{"id":"ga68-dotatate-then-lutathera","kind":"pairing","name":"68Ga-DOTATATE PET before Lutathera (177Lu-DOTATATE)","aka":[],"tldr":"Before starting the neuroendocrine tumour treatment Lutathera, patients get a somatostatin-receptor PET scan to confirm the tumour actually has the right target for the drug to lock onto. Lutathera's approval and use are built around this scan-first rule.","summary":"Lutathera (177Lu-dotatate) is FDA-approved for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, and its own label states that eligibility in the pivotal programme required 'confirmed presence of somatostatin receptors on all lesions,' historically demonstrated with OctreoScan (111In-pentetreotide) uptake at least equal to normal liver, and now more commonly with PET agents such as 68Ga-DOTATATE, 68Ga-DOTATOC or 64Cu-DOTATATE, which have largely replaced OctreoScan because of higher sensitivity and better lesion detectability. Lesions with tracer uptake less than liver activity are considered somatostatin-receptor-negative and are not expected to respond to Lutathera; patients with significant somatostatin-receptor-negative (and, where available, FDG-positive) disease are generally excluded from treatment because such discordant lesions predict poor response to PRRT.\n\nThis is a drug-specific instance of the broader diagnostic-therapeutic 'theranostic' pairing between somatostatin-receptor PET and peptide receptor radionuclide therapy: the same molecular target (SSTR2) is imaged with a gallium-68- or copper-64-labelled diagnostic tracer and then treated with the lutetium-177-labelled therapeutic analogue, so the scan used for staging doubles as the biomarker test that selects patients for, and later monitors response to, Lutathera. SNMMI/EANM and society guidance recommend repeat somatostatin-receptor PET roughly 3-6 months after completing PRRT to assess response.\n\nEligibility based on receptor imaging (Krenning score equivalent, uptake greater than liver) sits alongside other selection criteria in the Lutathera label and NET treatment guidelines, including Ki-67 index, performance status, renal function and prior PRRT exposure. This record is specific to the Lutathera-DOTATATE PET pairing and is distinct from the generic sstr-pet-to-prrt technology-level pairing already in this graph, which covers somatostatin receptor PET's relationship to PRRT as a modality rather than the specific FDA-labelled drug requirement.","asOf":"2026-09-22","links":[{"label":"FDA label: Lutathera (lutetium Lu 177 dotatate), 2024 revision, eligibility criteria","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/208700Orig1s032lbl.pdf"},{"label":"SNMT practical considerations for 177Lu-DOTATATE programmes: SSTR imaging and patient selection","url":"https://tech.snmjournals.org/content/jnmt/early/2022/06/14/jnmt.122.263813.full.pdf"},{"label":"Clinical guide to PRRT with 177Lu-DOTATATE (PMC9737149)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9737149/"}],"tags":["neuroendocrine tumours","theranostics","patient selection"],"related":["sstr2","neuroendocrine","sstr-pet","prrt","sstr-pet-to-prrt","richard-baum","ga-68","in-111","cu-64","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"ga68-dotatate","b":"lutathera","rationale":"Lutathera targets the same somatostatin receptor (SSTR2) that 68Ga-DOTATATE PET images, so the diagnostic scan doubles as the biomarker test confirming a tumour expresses enough receptor to be worth treating, and later as the response-assessment tool.","evidence":"Lutathera's FDA label states eligibility required 'confirmed presence of somatostatin receptors on all lesions', historically shown by OctreoScan uptake at least equal to liver, now more often confirmed on 68Ga-DOTATATE PET; lesions with uptake below liver activity are considered SSTR-negative and unlikely to respond to PRRT.","pairingType":"diagnostic-therapeutic","route":"/pairings/ga68-dotatate-then-lutathera/"}
{"id":"paper-therap-lancet-2021","kind":"paper","name":"TheraP: [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer","aka":[],"tldr":"In men whose prostate cancer had grown after chemotherapy, a radioactive drug that homes in on prostate cancer cells (lutetium-177 PSMA-617) shrank the PSA marker in more men, and caused fewer serious side effects, than the standard chemotherapy drug it was compared with.","summary":"TheraP (ANZUP 1603) was an open-label, randomised phase 2 trial at 11 Australian centres. Men with metastatic castration-resistant prostate cancer progressing after docetaxel, selected by centrally reviewed 68Ga-PSMA-11 and FDG PET/CT (excluding FDG-positive/PSMA-negative discordant disease), were randomised 1:1 to [177Lu]Lu-PSMA-617 (6.0-8.5 GBq IV every 6 weeks, up to six cycles) or cabazitaxel (20 mg/m2 IV every 3 weeks, up to ten cycles). The primary endpoint was a PSA50 response.\n\nOf 291 men screened, 200 were PET-eligible and randomised. PSA50 responses were 66% with 177Lu-PSMA-617 versus 37% with cabazitaxel by intention to treat (difference 29 percentage points, 95% CI 16-42, p<0.0001). Grade 3-4 adverse events were less frequent with the radioligand (33% versus 53%). A mature follow-up analysis (Hofman et al., Lancet Oncology 2024) found overall survival was similar between arms (restricted mean survival time 19.1 versus 19.6 months), with substantial crossover (32% of the radioligand-therapy group and 20% of the cabazitaxel group went on to the other treatment).\n\nTheraP was the first randomised trial to compare a PSMA radioligand head-to-head against a standard chemotherapy and used PET-based patient selection prospectively, a design later echoed by VISION and PSMAfore. It helped establish 177Lu-PSMA-617 (subsequently approved as Pluvicto) as a credible alternative to cabazitaxel in the post-docetaxel setting.","asOf":"2026-09-22","links":[{"label":"PubMed: TheraP primary results (Lancet 2021)","url":"https://pubmed.ncbi.nlm.nih.gov/33581798/"},{"label":"PubMed: TheraP overall survival (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/38043558/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["therap","vision","lu177-radioligand-therapy","pluvicto","psma-pet","cabazitaxel","prostate-mcrpc","michael-morris","hofman-michael","louise-emmett","sandhu-shahneen","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00237-3","pmid":"33581798","authors":"Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, et al.","paperType":"rct","findings":["PSA50 response: 66% (177Lu-PSMA-617) vs 37% (cabazitaxel) by intention to treat; difference 29% (95% CI 16-42), p<0.0001.","Grade 3-4 adverse events: 33% (98 men, PSMA arm) vs 53% (85 men, cabazitaxel arm); no deaths attributed to 177Lu-PSMA-617.","Mature follow-up (median 35.7 months): overall survival restricted mean survival time 19.1 months (PSMA) vs 19.6 months (cabazitaxel), difference -0.5 months (95% CI -3.7 to 2.7), p=0.77 - no evidence of an OS difference.","80 of 291 registered men (27%) were excluded after PET screening for low PSMA expression or FDG-discordant disease; their median survival was substantially shorter (RMST 11.0 months)."],"whatItMeans":"For men whose prostate cancer has grown after chemotherapy, a PSMA-targeted radioactive treatment worked at least as well as, and was gentler than, the chemotherapy drug it replaced - provided a PET scan first confirms the cancer takes up the PSMA tracer.","caveats":["Phase 2, single-country (Australia), open-label, not powered for overall survival as a primary endpoint.","High crossover between arms after the randomised period complicates the survival comparison.","PET-based selection excluded over a quarter of screened men, whose prognosis was worse regardless of treatment - the trial says nothing about that PSMA-negative group."],"changedPractice":true,"participants":200,"route":"/key-papers/paper-therap-lancet-2021/"}
{"id":"paper-psmafore-lancet-2024","kind":"paper","name":"PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC","aka":[],"tldr":"In men with advanced prostate cancer who had not yet had chemotherapy but whose disease had grown on one hormone-blocking drug, switching to the radioactive PSMA treatment kept the cancer under control for longer than switching to a different hormone drug.","summary":"PSMAfore was a phase 3, randomised, controlled, open-label trial at 74 sites in Europe and North America. Taxane-naive men with PSMA-positive metastatic castration-resistant prostate cancer who had progressed once on an androgen receptor pathway inhibitor (ARPI) were randomised 1:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for six cycles) or a change of ARPI (abiraterone or enzalutamide). Crossover to 177Lu-PSMA-617 was permitted after confirmed radiographic progression on ARPI change. The primary endpoint was radiographic progression-free survival (rPFS).\n\nOf 468 randomised men, updated analysis (median follow-up ~24 months) showed median rPFS of 11.6 months with 177Lu-PSMA-617 versus 5.6 months with ARPI change (HR 0.49, 95% CI 0.39-0.61). The final overall survival analysis (Ann Oncol 2025) found no significant intention-to-treat difference (24.5 vs 23.1 months, HR 0.91, p=0.20), heavily confounded by a 60% crossover rate from the control arm; a crossover-adjusted analysis suggested benefit (HR 0.59). Grade 3+ and serious adverse events were less frequent with 177Lu-PSMA-617 than with ARPI change.\n\nPSMAfore moved PSMA radioligand therapy earlier in the treatment sequence - before chemotherapy - and was the evidentiary basis, alongside VISION, for regulators to consider extending 177Lu-PSMA-617 use to the pre-taxane setting.","asOf":"2026-09-22","links":[{"label":"PubMed: PSMAfore primary results (Lancet 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39293462/"},{"label":"PubMed: PSMAfore final overall survival (Ann Oncol 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/40680993/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["psmafore","vision","pluvicto","psma-pet","prostate-mcrpc","arpi","michael-morris","ken-herrmann","oliver-sartor","karim-fizazi","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01653-2","pmid":"39293462","authors":"Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, et al.","paperType":"rct","findings":["Updated analysis: median rPFS 11.6 months (177Lu-PSMA-617) vs 5.6 months (ARPI change); HR 0.49 (95% CI 0.39-0.61).","Primary analysis: median rPFS 9.3 months vs 5.55 months; HR 0.41 (95% CI 0.29-0.56), p<0.0001.","Final overall survival (intention to treat): 24.48 vs 23.13 months, HR 0.91 (95% CI 0.72-1.14), p=0.20; crossover-adjusted HR 0.59 (95% CI 0.38-0.91).","60.3% of men assigned to ARPI change crossed over to 177Lu-PSMA-617 after progression.","Grade 3+ treatment-emergent adverse events: 60.8 per 100 patient-treatment years (177Lu-PSMA-617) vs 85.1 (ARPI change)."],"whatItMeans":"For men who still have a working hormone treatment option but whose cancer is progressing, offering the PSMA radioligand therapy sooner - before chemotherapy - delayed disease progression, though it did not clearly extend how long men lived once the very high rate of patients switching over is accounted for.","caveats":["Open-label design and high crossover from control to experimental arm make the overall-survival comparison unreliable by intention to treat.","Crossover-adjusted survival analyses rely on modelling assumptions rather than randomisation.","Trial excluded men who had already had a taxane, so results do not generalise to post-chemotherapy patients (that population is VISION and TheraP)."],"changedPractice":true,"participants":468,"route":"/key-papers/paper-psmafore-lancet-2024/"}
{"id":"paper-zircon-lancet-oncol-2024","kind":"paper","name":"ZIRCON: [89Zr]Zr-girentuximab PET-CT for detecting clear-cell renal cell carcinoma","aka":[],"tldr":"A PET scan using a radioactively-labelled antibody could tell, without surgery, whether a suspicious kidney lump was the most common type of kidney cancer - correctly in about 9 out of 10 people.","summary":"ZIRCON was a prospective, open-label, multicentre phase 3 trial at 36 sites in nine countries. Adults with an indeterminate renal mass of 7 cm or less (cT1), suspicious for clear-cell renal cell carcinoma (ccRCC) and scheduled for nephrectomy, received a single dose of [89Zr]Zr-girentuximab (37 MBq, 10 mg antibody) intravenously, followed by PET-CT 5 (±2) days later. Blinded central histopathological review of the surgical specimen was the reference standard. Co-primary endpoints were sensitivity and specificity for ccRCC detection.\n\nOf 332 enrolled patients, 300 received the tracer and 284 were evaluable in the primary analysis. Mean sensitivity was 85.5% (95% CI 81.5-89.6) and mean specificity was 87.0% (81.0-93.1) across three independent readers; positive predictive value was around 93%. The safety profile was favourable: most adverse events occurred peri-operatively and were unrelated to the tracer, with no treatment-related deaths.\n\n[89Zr]Zr-girentuximab (TLX250-CDx, Telix Pharmaceuticals) targets carbonic anhydrase IX (CAIX), which is highly expressed in ccRCC but not in other renal-mass pathologies (oncocytoma, papillary or chromophobe RCC, angiomyolipoma). Non-invasive discrimination of ccRCC from these mimics could reduce unnecessary biopsies and nephrectomies and guide a choice between surveillance and surgery for small renal masses - though as of this record's date the agent had not yet received a marketing authorisation.","asOf":"2026-09-22","links":[{"label":"PubMed: ZIRCON trial (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Telix Pharmaceuticals: ZIRCON results announcement","url":"https://telixpharma.com/news-views/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology/"}],"tags":["renal cell carcinoma","PET imaging","CAIX"],"related":["girentuximab-zr89","caix-pet","rcc","immuno-pet","telix","zr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2024,"doi":"10.1016/S1470-2045(24)00402-9","pmid":"39270701","authors":"Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, et al.","paperType":"rct","findings":["Mean sensitivity for ccRCC detection: 85.5% (95% CI 81.5-89.6); mean specificity: 87.0% (95% CI 81.0-93.1) across three blinded central readers.","Positive predictive value approximately 93%, including in small and difficult-to-detect lesions (per company summary of the same dataset).","No treatment-related deaths; most adverse events (74%) occurred during or after surgery and were unrelated to the tracer.","Most common grade 3+ adverse events were post-procedural haemorrhage (2%), urinary retention (1%) and hypertension (1%), attributable to the surgery rather than the tracer."],"whatItMeans":"A single injection and a PET scan five days later can identify clear-cell kidney cancer accurately enough to help decide whether someone with a suspicious kidney lump needs surgery, avoiding some biopsies and unnecessary operations.","caveats":["All participants were already scheduled for nephrectomy, so the trial does not directly show the agent changes management in a broader population of patients under surveillance.","As of the paper's publication the agent (TLX250-CDx / Zircaix) was investigational, not approved by FDA or EMA.","Performance in masses larger than 7 cm, or in patients unfit for surgery, was not the focus of this trial."],"changedPractice":false,"participants":300,"route":"/key-papers/paper-zircon-lancet-oncol-2024/"}
{"id":"paper-kratochwil-ac225-psma-jnm-2016","kind":"paper","name":"225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer","aka":[],"tldr":"The first published report of two men with very advanced prostate cancer, who had run out of other options, having their cancer disappear on scans after treatment with an alpha-emitting radioactive drug aimed at PSMA.","summary":"This case report from Heidelberg described the first-in-human use of 225Ac-PSMA-617, an alpha-particle-emitting version of the PSMA-617 ligand used with the beta-emitter lutetium-177. Two men with metastatic castration-resistant prostate cancer in clinically critical situations - one for whom beta-emitter therapy was contraindicated by diffuse bone marrow infiltration, one who had become resistant to 177Lu-PSMA-617 - were treated with 100 kBq of 225Ac-PSMA-617 per kilogram of body weight, given roughly every two months, after 68Ga-PSMA-11 PET/CT confirmed a PSMA-positive tumour phenotype.\n\nBoth patients had PSA fall to below the detectable level and achieved a complete response on repeat 68Ga-PSMA-11 PET/CT imaging, with no relevant haematological toxicity. Xerostomia (dry mouth), from radiation to the salivary glands (which also express PSMA), was the only notable side effect.\n\nAlthough based on only two patients, this report is widely cited as the proof of concept that launched clinical development of actinium-225-labelled PSMA radioligands as a next-generation, more potent alternative to beta-emitter therapy for men who fail or cannot tolerate 177Lu-PSMA-617. It also flagged salivary gland toxicity as the principal dose-limiting problem for PSMA-targeted alpha therapy, a theme followed up in the authors' subsequent dosimetry and dose-finding papers (2017, 2018).","asOf":"2026-09-22","links":[{"label":"JNM: 225Ac-PSMA-617 first-in-human report (full text PDF)","url":"https://jnm.snmjournals.org/content/jnumed/57/12/1941.full.pdf"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/27389577/"}],"tags":["alpha therapy","prostate cancer","first-in-human"],"related":["ac225-psma","targeted-alpha-therapy","psma","prostate-mcrpc","clemens-kratochwil","uwe-haberkorn","beta-then-alpha","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2016,"doi":"10.2967/jnumed.116.178673","pmid":"27389577","authors":"Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, et al.","paperType":"observational","findings":["Both patients achieved a PSA decline to below the measurable level and a complete response on 68Ga-PSMA-11 PET/CT restaging.","No relevant haematological toxicity was observed at 100 kBq/kg per cycle, dosed roughly every 8 weeks.","Xerostomia was the only notable clinical side effect reported."],"whatItMeans":"This was the first evidence, in two patients, that attaching a more powerful (alpha-emitting) form of radiation to the same PSMA-seeking molecule used in lutetium-177 PSMA therapy could produce a complete response even in prostate cancer that had already stopped responding to the beta-emitter version.","caveats":["Only two patients; no control group, no survival data, and no formal toxicity study - this is hypothesis-generating, not proof of benefit.","225Ac-PSMA-617 remains investigational; as of this record's date it had not been approved by FDA or EMA and is used mainly under compassionate access or in trials.","Long-term xerostomia and renal toxicity risks were characterised in later, larger series, not in this initial report."],"changedPractice":false,"participants":2,"route":"/key-papers/paper-kratochwil-ac225-psma-jnm-2016/"}
{"id":"paper-strosberg-netter1-qol-jco-2018","kind":"paper","name":"Health-related quality of life in the NETTER-1 trial of 177Lu-Dotatate","aka":[],"tldr":"In people with a slow-growing gut cancer, the radioactive treatment lutetium-177 dotatate did not just shrink tumours for longer - it also kept their day-to-day quality of life, including energy, pain and diarrhoea, better for much longer than the older drug it was compared with.","summary":"This is the health-related quality-of-life (HRQoL) analysis of NETTER-1, the phase 3 trial that established 177Lu-Dotatate (Lutathera) for progressive midgut neuroendocrine tumours. Patients (117 on 177Lu-Dotatate, 114 on high-dose octreotide) completed the EORTC QLQ-C30 and GI.NET-21 questionnaires at baseline and every 12 weeks. Time to deterioration (TTD), defined as a fall of 10 points or more from baseline in a domain, was compared between arms by intention to treat.\n\nTTD was significantly longer with 177Lu-Dotatate across every domain tested: global health status (HR 0.406), physical functioning (HR 0.518), role functioning (HR 0.580), fatigue (HR 0.621), pain (HR 0.566), diarrhoea (HR 0.473), disease-related worries (HR 0.572) and body image (HR 0.425). The difference in median TTD was large in absolute terms - 28.8 months versus 6.1 months for global health status, and 25.2 versus 11.5 months for physical functioning.\n\nBecause NETTER-1's primary endpoint (progression-free survival) had already shown a large benefit, this paper mattered for showing the benefit was not bought at the cost of how patients felt day to day - in every domain measured, 177Lu-Dotatate patients did the same or better than those on high-dose octreotide, never worse. It is frequently cited alongside the primary NETTER-1 report to support PRRT's tolerability case to patients and payers.","asOf":"2026-09-22","links":[{"label":"PubMed: NETTER-1 quality-of-life analysis (JCO 2018)","url":"https://pubmed.ncbi.nlm.nih.gov/29878866/"},{"label":"ASCO Publications: full text","url":"https://ascopubs.org/doi/10.1200/JCO.2018.78.5865"}],"tags":["neuroendocrine tumours","PRRT","quality of life"],"related":["netter-1","paper-netter-1-nejm-2017","lutathera","prrt","small-intestinal-net","jonathan-strosberg","richard-baum","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO","year":2018,"doi":"10.1200/JCO.2018.78.5865","pmid":"29878866","authors":"Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, et al.","paperType":"rct","findings":["Time to QoL deterioration (10-point fall) was significantly longer with 177Lu-Dotatate than high-dose octreotide across all measured domains.","Global health status: median TTD 28.8 months (177Lu-Dotatate) vs 6.1 months (octreotide); HR 0.406, p<0.001.","Physical functioning: median TTD 25.2 vs 11.5 months; HR 0.518.","Diarrhoea (HR 0.473), fatigue (HR 0.621) and pain (HR 0.566) all deteriorated significantly later on 177Lu-Dotatate."],"whatItMeans":"People treated with the radioactive drug lutetium-177 dotatate kept feeling well for much longer - years rather than months, in several measures - than people on the standard high-dose hormone injection, on top of the tumour-control benefit already shown.","caveats":["Quality-of-life data are patient-reported and unblinded (the trial was open-label), which can bias favourable results toward the novel treatment.","Questionnaires were completed only until disease progression, so long-term quality of life beyond that point is not captured here.","This is a secondary/exploratory endpoint analysis of NETTER-1, not an independently powered trial."],"changedPractice":true,"participants":231,"route":"/key-papers/paper-strosberg-netter1-qol-jco-2018/"}
{"id":"paper-hofman-lupsma-lancet-oncol-2018","kind":"paper","name":"LuPSMA trial: single-arm phase 2 study of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer","aka":[],"tldr":"In an early single-hospital study, most men with advanced prostate cancer who had run out of standard treatments saw their PSA fall by at least half after being treated with the radioactive drug lutetium-177 PSMA-617, with mild side effects.","summary":"Conducted at Peter MacCallum Cancer Centre, Melbourne, this single-arm, single-centre phase 2 trial treated men with metastatic castration-resistant prostate cancer who had progressed after taxane chemotherapy and second-generation anti-androgens. Screening 68Ga-PSMA-11 and FDG PET/CT confirmed high PSMA expression before treatment; eligible men received up to four cycles of 177Lu-PSMA-617 (mean 7.5 GBq per cycle) six weeks apart. Endpoints were PSA response (≥50% decline), imaging response, toxicity and quality of life.\n\nOf 43 men screened, 30 were treated. Seventeen of 30 (57%, 95% CI 37-75) had a PSA decline of 50% or more. Objective response in nodal or visceral disease was seen in 14 of 17 (82%) evaluable patients. Toxicity was mostly low grade (dry mouth in 87%, transient nausea and fatigue in 50%), though grade 3-4 thrombocytopenia occurred in 13%. Clinically meaningful pain and global-health-score improvements were recorded from the second cycle onward in over a third of patients.\n\nThis was one of the pivotal early single-arm studies (alongside German centres' compassionate-use experience) that generated the response-rate and toxicity signal used to justify the subsequent randomised trials TheraP and VISION, and it is one of the most-cited early efficacy reports for PSMA radioligand therapy.","asOf":"2026-09-22","links":[{"label":"PubMed: LuPSMA trial (Lancet Oncol 2018)","url":"https://pubmed.ncbi.nlm.nih.gov/29752180/"}],"tags":["prostate cancer","radioligand therapy","phase 2"],"related":["therap","vision","lu177-radioligand-therapy","psma-pet","prostate-mcrpc","hofman-michael","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30198-0","pmid":"29752180","authors":"Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, et al.","paperType":"observational","findings":["17 of 30 patients (57%, 95% CI 37-75) achieved a PSA decline of 50% or more.","Objective response in nodal or visceral disease in 14 of 17 (82%) evaluable patients.","Grade 1 dry mouth in 87%, grade 1-2 nausea and fatigue each in 50%; grade 3-4 thrombocytopenia in 13% (4 of 30).","37% of patients had a 10-point or greater improvement in global health score by the second treatment cycle; no treatment-related deaths."],"whatItMeans":"In a small early trial, most heavily pre-treated men with advanced prostate cancer responded to the PSMA-targeted radioactive drug, with manageable side effects, supporting the case for testing it in larger randomised trials.","caveats":["Single-arm, single-centre design with no comparator - response rates cannot be attributed to the drug alone with the same confidence as a randomised trial.","Small sample size (30 treated patients) limits precision of toxicity estimates, particularly for rarer serious events.","Patients were required to have high PSMA expression on screening PET, so results do not apply to PSMA-low disease."],"changedPractice":true,"participants":30,"route":"/key-papers/paper-hofman-lupsma-lancet-oncol-2018/"}
{"id":"paper-sgouros-tat-review-nat-rev-2020","kind":"paper","name":"Radiopharmaceutical therapy in cancer: clinical advances and challenges","aka":[],"tldr":"A review, written for drug developers, of how radioactive cancer drugs work, which ones had reached patients by 2020, and what stands in the way of making more of them.","summary":"This review by Sgouros, Bodei, McDevitt and Nedrow surveys the state of radiopharmaceutical therapy (RPT) as of 2020: the physics of alpha, beta and Auger emitters, the targeting chemistry (small molecules, peptides, antibodies), the theranostic pairing of imaging and therapy isotopes, and the clinical evidence behind approved and late-stage agents (iodine-131, radium-223, lutetium-177 dotatate, and the then-emerging lutetium-177 and actinium-225 PSMA agents). It frames RPT's central advantage - imageable biodistribution paired with cytotoxic effect, and a favourable toxicity profile relative to most systemic cytotoxic therapies - and its central bottlenecks: isotope supply, dosimetry standardisation, and the absence of a companion-diagnostic regulatory pathway equivalent to that for drugs.\n\nThe review does not report new clinical data; its contribution is a structured account of the field's trajectory and the translational problems (manufacturing scale, radiobiology of low dose-rate irradiation, patient selection biomarkers) that a decade of subsequent approvals (Pluvicto, Lutathera label expansions) had to solve.\n\nIt is widely cited as a field-level reference in subsequent radiopharmaceutical papers and grant applications, alongside the companion 2020 Lancet Oncology roadmap by Herrmann and colleagues.","asOf":"2026-09-22","links":[{"label":"Nature Reviews Drug Discovery: full text","url":"https://www.nature.com/articles/s41573-020-0073-9"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/32728207/"}],"tags":["review","radiopharmaceutical therapy"],"related":["targeted-alpha-therapy","radioligand-therapy","therapy-isotope-supply-chain","radioligand-dosimetry","theranostics","lu-177","ac-225","ra-223","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2020,"doi":"10.1038/s41573-020-0073-9","pmid":"32728207","authors":"Sgouros G, Bodei L, McDevitt MR, Nedrow JR","paperType":"review","findings":["Surveys approved and late-stage radiopharmaceutical therapies as of 2020 (iodine-131, radium-223, 177Lu-dotatate, emerging PSMA agents) and their radiobiological basis.","Identifies isotope supply, standardised dosimetry, and regulatory pathways for companion imaging diagnostics as the principal translational bottlenecks for the field.","Frames radiopharmaceutical therapy's comparative advantage as imageable biodistribution combined with generally lower toxicity than systemic cytotoxic chemotherapy."],"whatItMeans":"This paper is a map of the radioactive-cancer-drug field at a pivotal moment, explaining to non-specialists and drug developers alike why these treatments work differently from chemotherapy and what needed to be fixed - supply, dosing science, regulation - before more of them could reach patients.","caveats":["As a narrative review, it synthesises published data rather than presenting new trial results, and reflects the evidence base and pipeline as they stood in 2020.","Note the journal is Nature Reviews Drug Discovery (the corpus records this under the closest matching journal entry, Nature Medicine, as Nature Reviews Drug Discovery is not separately catalogued); consult the DOI/PMID for the exact source."],"changedPractice":false,"route":"/key-papers/paper-sgouros-tat-review-nat-rev-2020/"}
{"id":"paper-herrmann-radiotheranostics-lancet-oncol-2020","kind":"paper","name":"Radiotheranostics: a roadmap for future development","aka":[],"tldr":"A group of leading nuclear medicine specialists set out, in one article, what needs to happen - in science, manufacturing, regulation and training - for more radioactive scan-and-treat drugs to reach patients over the following five years.","summary":"This roadmap article, led by Ken Herrmann with co-authors including Jason Lewis, argues that radiotheranostics - radiopharmaceuticals that both image and treat the same molecular target - had reached an inflection point by 2020, with several agents already approved and many more in the pipeline. Rather than reporting new trial data, it lays out the practical barriers standing in the way of that pipeline reaching patients: logistics of a decaying drug (short shelf life, need for rapid distribution), isotope supply chains, the absence of harmonised regulatory frameworks for paired diagnostic-therapeutic products, reimbursement, and the shortage of trained nuclear medicine physicians and technologists.\n\nThe authors call for multidisciplinary clinical trial designs that pair imaging biomarker development with therapeutic dose-finding from the outset, rather than treating the diagnostic and therapeutic halves of a theranostic pair as separate regulatory programmes.\n\nPublished in the same year as the FDA approval of 177Lu-dotatate's expanded indications and shortly before the VISION trial results, it is frequently cited as a statement of the field's ambitions and obstacles just before radioligand therapy entered mainstream oncology practice with Pluvicto's 2022 approval.","asOf":"2026-09-22","links":[{"label":"The Lancet Oncology: article","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30821-6/abstract"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/32135118/"}],"tags":["review","roadmap","theranostics"],"related":["theranostics","therapy-isotope-supply-chain","radiopharmaceutical-gmp-release","radiopharmacy-network","ken-herrmann","jason-lewis","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(19)30821-6","pmid":"32135118","authors":"Herrmann K, Schwaiger M, Lewis JS, Solomon SB, McNeil BJ, et al.","paperType":"review","findings":["Identifies logistics of short-half-life radiopharmaceuticals, isotope supply, and fragmented regulatory pathways for paired diagnostic-therapeutic products as the main barriers to radiotheranostics reaching more patients.","Calls for trial designs that integrate imaging-biomarker qualification with therapeutic dose-finding rather than developing the diagnostic and therapeutic halves separately.","Flags workforce shortages in nuclear medicine training as a practical constraint on scaling radiotheranostics services."],"whatItMeans":"This article is a call to action from senior nuclear medicine physicians: the treatments were becoming ready, but hospitals, regulators and isotope suppliers were not yet organised to deliver them at scale - a warning that proved accurate when demand for lutetium-177 PSMA therapy outstripped supply after 2022.","caveats":["An expert roadmap and opinion piece, not a systematic review or trial report; recommendations reflect the authors' priorities rather than a formal consensus process.","Written before the VISION trial and Pluvicto's approval, so some of its forward-looking statements have since been superseded by events."],"changedPractice":false,"route":"/key-papers/paper-herrmann-radiotheranostics-lancet-oncol-2020/"}
{"id":"paper-baum-prrt-1048-patients-oncotarget-2018","kind":"paper","name":"Results and adverse events of personalised peptide receptor radionuclide therapy in 1048 patients with neuroendocrine neoplasms","aka":[],"tldr":"The largest single-centre report of a radioactive treatment for neuroendocrine tumours, from over a thousand patients treated across a decade at one German hospital, showing typical survival times and how often serious side effects such as blood cancers occurred.","summary":"This retrospective single-centre analysis from Zentralklinik Bad Berka, Germany, reports outcomes for 1048 patients with neuroendocrine neoplasms treated with personalised peptide receptor radionuclide therapy (PRRT) using 90Y- and/or 177Lu-labelled somatostatin analogues between 2004 and 2014, drawn from 2294 patients screened by 68Ga-SSTR PET/CT. Radionuclide, dose and cycle number were individualised to tumour and organ dosimetry rather than fixed, reflecting the Bad Berka group's long-standing personalised-dosimetry approach to PRRT, predating the fixed four-cycle regimen later used in NETTER-1.\n\nMedian overall survival across all patients was 51 months (95% CI 47.0-54.9), varying significantly by radionuclide used, tumour grade, prior therapies and tumour origin (for example, gastrinoma and glucagonoma patients had median survival of 66 and 127 months respectively; insulinoma patients 32 months). Median progression-free survival (by 68Ga-SSTR PET/CT with EORTC criteria) was 19 months. Myelodysplastic syndrome or leukaemia developed in 22 patients (2.1%), and five patients required haemodialysis after treatment; other serious adverse events were rare.\n\nAs one of the largest published PRRT cohorts, and predating the randomised NETTER-1 trial, this paper was widely cited as real-world evidence for PRRT's long-term safety and effectiveness, and its dosimetry-personalised approach is a touchstone for the ongoing debate about fixed-activity versus dosimetry-guided PRRT dosing.","asOf":"2026-09-22","links":[{"label":"PMC: full text","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5908296/"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/29682217/"}],"tags":["neuroendocrine tumours","PRRT","real-world evidence"],"related":["prrt","lutathera","neuroendocrine","radioligand-dosimetry","richard-baum","paper-netter-1-nejm-2017","ga-68","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Oncotarget","year":2018,"doi":"10.18632/oncotarget.24524","pmid":"29682217","authors":"Baum RP, Kulkarni HR, Singh A, Kaemmerer D, Mueller D, et al.","paperType":"observational","findings":["Median overall survival across all 1048 patients: 51 months (95% CI 47.0-54.9), varying by radionuclide, tumour grade, prior therapies and site of origin.","Median progression-free survival by 68Ga-SSTR PET/CT: 19 months overall.","Myelodysplastic syndrome or leukaemia developed in 22 of 1048 patients (2.1%); 5 patients required haemodialysis after treatment.","Survival varied widely by tumour subtype: gastrinoma 66 months and glucagonoma 127 months median OS, versus insulinoma 32 months."],"whatItMeans":"In the largest reported group of neuroendocrine tumour patients treated with individually dosed radioactive peptide therapy, most people lived several years after treatment, and serious long-term harms such as blood cancers were uncommon but real, occurring in about 1 in 50 patients.","caveats":["Retrospective, single-centre, uncontrolled cohort - there is no comparator arm, so the survival figures cannot be attributed to PRRT alone.","Radionuclide choice, dose and cycle number were personalised per patient rather than fixed, so results may not generalise directly to fixed-activity regimens such as the one used in NETTER-1 or Lutathera's approved label.","Long recruitment period (2004-2014) spans changes in imaging, patient selection and supportive care that could affect outcomes over time."],"changedPractice":false,"participants":1048,"route":"/key-papers/paper-baum-prrt-1048-patients-oncotarget-2018/"}
{"id":"paper-jadvar-snmmi-psma-auc-jnm-2022","kind":"paper","name":"Appropriate use criteria for prostate-specific membrane antigen (PSMA) PET imaging","aka":[],"tldr":"A panel of cancer and imaging specialists agreed, scenario by scenario, when a PSMA PET scan for prostate cancer is a good idea and when it usually is not - a reference clinicians and insurers use to decide who should get the scan.","summary":"Following FDA approval of the first PSMA PET tracers (68Ga-PSMA-11 and 18F-DCFPyL) in 2020-2021, SNMMI convened a multidisciplinary panel - with the American College of Nuclear Medicine, American Urological Association, ANZSNM, ASCO, EANM and American College of Physicians - to produce appropriate use criteria (AUC) for PSMA PET in prostate cancer, using a RAND/UCLA-style consensus process. The panel scored defined clinical scenarios from 1 (rarely appropriate) to 9 (appropriate).\n\nPSMA PET was rated appropriate (score 8-9) for staging newly diagnosed unfavourable-intermediate, high- or very-high-risk prostate cancer (including when conventional imaging is negative or equivocal), for working up a PSA rise after prostatectomy or radiotherapy (biochemical recurrence), for non-metastatic castration-resistant disease on conventional imaging, and - critically - for confirming eligibility for PSMA-targeted radioligand therapy (score 9). It was rated rarely appropriate (score 2-3) for detecting or characterising the primary tumour in men with suspected but unbiopsied prostate cancer, or in very low/low/favourable-intermediate risk disease.\n\nThe document became the reference used by payers and referring clinicians to decide when a PSMA PET scan is billable and clinically justified, and its scenario 11 (eligibility for PSMA radioligand therapy) directly operationalises how VISION- and TheraP-style PET selection criteria are applied in routine practice.","asOf":"2026-09-22","links":[{"label":"SNMMI: PSMA PET Appropriate Use Criteria (PDF)","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Appropriate%20Use%20Criteria/PSMA%20AUC%202022.03.15_final_BOD%20approved.pdf"},{"label":"SNMMI: AUC overview page","url":"https://snmmi.org/Web/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate-Use-Criteria-for-Prostate-Specific-Membrane-Antigen--PSMA--PET-Imaging.aspx"}],"tags":["guideline","PSMA PET","appropriate use criteria"],"related":["psma-pet","ga68-psma-11","pylarify","prostate","prostate-bcr","prostate-mcrpc","psma-pet-to-rlt","eanm","snmmi","jeremie-calais","f-18","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2022,"doi":"10.2967/jnumed.121.263262","pmid":"34531258","authors":"Jadvar H, Calais J, Fanti S, Feng F, Greene KL, et al.","paperType":"guideline","findings":["PSMA PET rated appropriate (score 8) for staging newly diagnosed unfavourable-intermediate, high- or very-high-risk prostate cancer.","PSMA PET rated appropriate (score 9) for PSA rise after prostatectomy or radiotherapy (biochemical recurrence) and for confirming eligibility for PSMA-targeted radioligand therapy.","PSMA PET rated rarely appropriate (score 2-3) for detecting intraprostatic tumour in men with suspected but unbiopsied cancer, and for very low/low/favourable-intermediate-risk disease.","Panel included representatives from SNMMI, American College of Nuclear Medicine, American College of Physicians, ASCO, American Urological Association, ANZSNM and EANM."],"whatItMeans":"This guideline tells doctors and insurers exactly which clinical situations justify a PSMA PET scan for prostate cancer - mainly staging higher-risk disease, investigating a PSA rise after treatment, and checking that a patient's cancer will respond to PSMA radioligand therapy - and which situations do not.","caveats":["Appropriate use criteria reflect expert consensus and the evidence available in 2022; they are updated periodically and score some scenarios only as 'may be appropriate', reflecting genuine uncertainty rather than a firm answer.","Scores were assigned per clinical scenario, not per specific PSMA tracer; the panel treated different PSMA PET agents as broadly equivalent."],"changedPractice":true,"route":"/key-papers/paper-jadvar-snmmi-psma-auc-jnm-2022/"}
{"id":"paper-eanm-lu177-dosimetry-recommendations-ejnmmi-2022","kind":"paper","name":"EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands","aka":[],"tldr":"European nuclear medicine physicists set out a detailed, agreed method for measuring exactly how much radiation dose a patient's kidneys and tumours actually receive during lutetium-177 treatments, so that dosing can eventually be tailored to the individual rather than fixed for everyone.","summary":"This EANM Dosimetry Committee document provides detailed, practical recommendations for performing patient-specific dosimetry during therapy with 177Lu-labelled somatostatin-receptor ligands (for neuroendocrine tumours) and 177Lu-PSMA ligands (for prostate cancer). It specifies imaging protocols (typically three well-separated SPECT/CT time points per cycle for kidney and tumour dosimetry), segmentation and recovery-correction methods, and reports the underlying pharmacokinetic and dosimetric literature: mean kidney absorbed doses of roughly 0.54-1.00 Gy/GBq for 177Lu-somatostatin-receptor ligands and 0.4-0.8 Gy/GBq for 177Lu-PSMA, and tumour absorbed doses typically 1-8 Gy/GBq, with inter-patient variability up to ninefold for 177Lu-PSMA.\n\nThe guideline notes that because 177Lu-PSMA-617 (Pluvicto) is approved for use at a fixed activity per cycle (7.4 GBq every 6 weeks), patient-specific dosimetry is not mandatory for on-label use, but the committee encourages its practice to build the evidence base for eventually personalising dose - an approach already used for decades in dosimetry-led PRRT centres.\n\nThis document, alongside the companion joint EANM/SNMMI 177Lu-PSMA-RLT procedure guideline, is the reference clinical physicists and nuclear medicine physicians use to standardise dosimetry methodology across centres, a prerequisite for any future trial of dosimetry-personalised versus fixed-activity radioligand therapy.","asOf":"2026-09-22","links":[{"label":"EANM: dosimetry guidelines overview","url":"https://eanm.org/publications/guidelines/overview/dosimetry/"},{"label":"PMC: full text","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9015994/"}],"tags":["guideline","dosimetry","lutetium-177"],"related":["radioligand-dosimetry","dosimetry","prrt","lu177-radioligand-therapy","pluvicto","eanm","gray-unit","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2022,"doi":"10.1007/s00259-022-05727-7","pmid":"35284969","authors":"Sjögreen Gleisner K, Chouin N, Gabina PM, Cicone F, Gnesin S, et al.","paperType":"guideline","findings":["Recommends kidney dosimetry using SPECT/CT at three well-separated time points between day 1 and day 7 after each therapy cycle.","Reports mean absorbed kidney doses of roughly 0.54-1.00 Gy/GBq for 177Lu-somatostatin-receptor ligands and 0.4-0.8 Gy/GBq for 177Lu-PSMA.","Reports mean tumour absorbed doses of approximately 1-8 Gy/GBq, with up to ninefold inter-patient variability for 177Lu-PSMA (range 0.09-0.84 Gy/GBq in one cited series).","Notes that patient-specific dosimetry is not mandatory for on-label 177Lu-PSMA-617 use, since it is approved at a fixed per-cycle activity."],"whatItMeans":"This document standardises how hospitals measure the actual radiation dose reaching a patient's kidneys and tumours during lutetium-177 treatment, laying the groundwork for shifting from a one-dose-fits-all schedule to treatment doses tailored to each patient's biology.","caveats":["Journal metadata note: the article was published in the European Journal of Nuclear Medicine and Molecular Imaging (2022;49(6):1778-1809); recorded here under Journal of Nuclear Medicine as the nearest catalogued match, so the DOI and PMID should be treated as authoritative for sourcing.","Recommendations are methodological guidance, not a mandate; dosimetry uptake still varies widely between centres and countries.","Absorbed-dose ranges cited are drawn from the pooled literature the committee reviewed, not from a single new dataset."],"changedPractice":true,"route":"/key-papers/paper-eanm-lu177-dosimetry-recommendations-ejnmmi-2022/"}
{"id":"paper-tagawa-ac225-j591-jco-2024","kind":"paper","name":"Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC","aka":[],"tldr":"The first human test of an alpha-emitting radioactive drug attached to an antibody (rather than a small molecule) against PSMA found a safe dose in men with advanced prostate cancer who had exhausted other treatments, and shrank the PSA marker in nearly half of them - including those whose cancer had already stopped responding to the more common lutetium-177 PSMA treatment.","summary":"This first-in-human phase 1 dose-escalation trial tested 225Ac-J591 - the anti-PSMA monoclonal antibody J591 labelled with the alpha emitter actinium-225 - as a single intravenous dose in 32 men with progressive metastatic castration-resistant prostate cancer who had received or were ineligible for taxane chemotherapy and an androgen receptor pathway inhibitor. Unlike PSMA-617 or PSMA-I&T, J591 is a full antibody rather than a small peptidomimetic ligand, giving different pharmacokinetics (slower clearance, longer tumour residence). Patients were treated across seven dose levels (13.3 to 93.3 kBq/kg) without pre-selection by PSMA PET.\n\nOne dose-limiting toxicity (grade 4 anaemia and thrombocytopenia) occurred at 80 kBq/kg; none occurred at the highest dose level tested (93.3 kBq/kg), so a maximum tolerated dose was not reached and the recommended phase 2 dose was set at the top studied level. Most high-grade adverse events were haematological and dose-related; non-haematological toxicity was generally low grade - a different pattern from PSMA-617-based alpha agents, where xerostomia (dry mouth) from salivary gland uptake dominates, since antibodies clear the salivary glands less than small-molecule ligands. Efficacy signals were encouraging for a phase 1, dose-finding, unselected population: 46.9% of patients had a PSA decline of 50% or more at some point, 34.4% had a confirmed PSA50 response, and 59.1% had control of circulating tumour cells, with responses seen regardless of prior 177Lu-PSMA exposure.\n\nAs one of the first published clinical results for an antibody-based (rather than small-molecule) PSMA alpha-emitter, this trial supports antibody-delivered alpha therapy as a second route to targeted alpha therapy in prostate cancer, potentially with a different toxicity trade-off (more marrow suppression, less xerostomia) than PSMA-617-based agents, and without requiring PSMA PET pre-selection.","asOf":"2026-09-22","links":[{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/37922438/"},{"label":"ASCO Publications: full text","url":"https://ascopubs.org/doi/10.1200/JCO.23.00573"}],"tags":["alpha therapy","prostate cancer","phase 1"],"related":["ac225-psma","targeted-alpha-therapy","psma","prostate-mcrpc","oliver-sartor","beta-then-alpha","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO","year":2024,"doi":"10.1200/JCO.23.00573","pmid":"37922438","authors":"Tagawa ST, Thomas C, Sartor AO, Sun M, Stangl-Kremser J, et al.","paperType":"rct","findings":["Recommended phase 2 dose was the highest studied level, 93.3 kBq/kg; maximum tolerated dose was not reached across seven dose levels.","One dose-limiting toxicity (grade 4 anaemia and thrombocytopenia) occurred, at 80 kBq/kg; none at the highest dose level.","46.9% of patients had a PSA decline of 50% or more at any time; 34.4% had a confirmed PSA50 response.","Circulating tumour cell count control occurred in 13 of 22 evaluable patients (59.1%); responses were seen regardless of prior 177Lu-PSMA treatment.","High-grade adverse events were predominantly haematological and radioactivity-dose related; non-haematological toxicity was generally low grade."],"whatItMeans":"An alpha-emitting radioactive drug built on a PSMA-targeting antibody, rather than the small-molecule ligands used in existing PSMA therapies, was safe enough to move into further testing and shrank PSA in roughly a third to a half of heavily pre-treated men, including some whose cancer had already stopped responding to lutetium-177 PSMA therapy.","caveats":["Small, single-arm, phase 1 dose-escalation trial (32 patients) - not designed or powered to show a survival or definitive efficacy benefit.","No PSMA PET pre-selection was used, unlike VISION and TheraP, so response rates are not directly comparable to those trials.","Blood toxicity (anaemia, thrombocytopenia) tracked with dose, which will need careful management as the drug moves into larger trials."],"changedPractice":false,"participants":32,"route":"/key-papers/paper-tagawa-ac225-j591-jco-2024/"}
{"id":"scott-tagawa","kind":"person","name":"Scott T. Tagawa","aka":["Scott Tagawa"],"tldr":"A cancer doctor at Weill Cornell in New York who has spent two decades testing PSMA-targeted radioactive treatments for prostate cancer, from the first antibody versions through to lutetium-177 PSMA-617.","summary":"Scott Tagawa is a genitourinary medical oncologist who has run early-phase trials of PSMA-targeted radioimmunotherapy since the 2000s, starting with the antibody 177Lu-J591 and continuing through the VISION trial of 177Lu-PSMA-617 (lutetium-177 vipivotide tetraxetan), where he was a co-investigator and author on subsequent safety and PSA-kinetics analyses. He is also a lead investigator on Trop-2-directed antibody-drug conjugate trials (TROPHY-U-01, TROPiCS-04) in urothelial cancer, giving him a cross-cutting view of radioligand and ADC approaches to genitourinary disease.\n\nAt Weill Cornell he directs the Genitourinary Oncology Program and the GU Oncology Research Program, and is the institution's principal investigator for the Alliance for Clinical Trials in Oncology. His group's early J591 dosimetry and fractionation studies helped establish the dose-response relationship for PSMA-targeted radioligand therapy that later informed 177Lu-PSMA-617 dosing.","asOf":"2026-09-22","links":[{"label":"Weill Cornell Medicine: Scott T. Tagawa","url":"https://weillcornell.org/sttagawa"},{"label":"VISION safety analysis, European Urology 2024","url":"https://www.sciencedirect.com/science/article/pii/S0302283824000206"}],"tags":["prostate","PSMA","clinician"],"related":["pluvicto","vision","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Medicine and Urology, and Director of the Genitourinary Oncology Program, Weill Cornell Medicine / NewYork-Presbyterian","specialisms":["genitourinary medical oncology","PSMA radioligand and radioimmunotherapy","antibody-drug conjugates"],"profiles":[{"label":"Weill Cornell Medicine profile","url":"https://weillcornell.org/sttagawa"},{"label":"Weill Cornell VIVO research profile","url":"https://vivo.weill.cornell.edu/display/cwid-stt2007"}],"papers":[{"title":"Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer","journal":"Clinical Cancer Research","year":2013,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3778101/"},{"title":"TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors","journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.03489"},{"title":"Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer","journal":"European Urology","year":2024,"url":"https://www.sciencedirect.com/science/article/pii/S0302283824000206"}],"route":"/people/scott-tagawa/"}
{"id":"neeta-pandit-taskar","kind":"person","name":"Neeta Pandit-Taskar","aka":[],"tldr":"A nuclear medicine doctor who spent 25 years at Memorial Sloan Kettering developing radioactive antibody treatments, including therapies for children with neuroblastoma, before moving to lead nuclear medicine at UPMC Hillman Cancer Center in 2025.","summary":"Neeta Pandit-Taskar joined Memorial Sloan Kettering Cancer Center (MSK) in 2000 and became Clinical Director of the Center for Radioimmunotargeted Imaging and Theranostics of the Ludwig Center for Cancer Immunotherapy, working on radiolabelled monoclonal antibodies and small molecules across lymphoma, prostate, renal and pancreatic cancers, and on 131I-omburtamab for paediatric leptomeningeal disease. In July 2025 she moved to become Chief of Nuclear Medicine and Vice-Chair of Clinical and Translational Research at UPMC Hillman Cancer Center and the University of Pittsburgh, also directing oncology imaging and theranostics there.\n\nShe served as president of the SNMMI Therapy Advisory Committee (Center for Molecular Imaging, Innovation, and Translation) from 2021 to 2023 and has advised the FDA and NRC on clinical use of actinium-225 alpha-emitting therapies. Her research spans imaging and therapy dosimetry for both antibody- and peptide-based radiopharmaceuticals, with particular depth in paediatric neuroblastoma imaging (18F-mFBG PET).","asOf":"2026-09-22","links":[{"label":"UPMC provider profile","url":"https://providers.upmc.com/provider/neeta-pandit-taskar/4210094"},{"label":"FDA-NRC Workshop presenter biography (actinium-225)","url":"https://www.fda.gov/media/152280/download"},{"label":"SNMMI Therapy Advisory Committee past presidents","url":"https://snmmi.org/AM/Web/About/About-SNMMI/Advisory-Committees/Therapy-Advisory-Committee/Past-Presidents.aspx"}],"tags":["theranostics","radioimmunotherapy","clinician"],"related":["mskcc","snmmi","neuroblastoma","f-18","ac-225","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chief of Nuclear Medicine and Vice-Chair of Clinical and Translational Research, UPMC Hillman Cancer Center / University of Pittsburgh (from July 2025; previously at Memorial Sloan Kettering Cancer Center, 2000-2025)","specialisms":["radioimmunotherapy","actinium-225 alpha therapy","paediatric nuclear medicine dosimetry"],"profiles":[{"label":"UPMC provider profile","url":"https://providers.upmc.com/provider/neeta-pandit-taskar/4210094"},{"label":"ORCID","url":"https://orcid.org/0000-0003-1551-2036"},{"label":"Former MSK profile (2000-2025)","url":"https://www.mskcc.org/cancer-care/doctors/neeta-pandit-taskar"}],"papers":[{"title":"Radioimmunoscintigraphy and pre-treatment dosimetry of 131I-omburtamab for planning treatment of leptomeningeal disease","journal":"Journal of Nuclear Medicine","year":2023,"doi":"10.2967/jnumed.122.265131"},{"title":"Safety Observations in Neuroblastoma Patients Undergoing 18F-mFBG PET","journal":"Nuclear Medicine Communications","year":2024,"doi":"10.1097/MNM.0000000000001938"}],"orcid":"0000-0003-1551-2036","route":"/people/neeta-pandit-taskar/"}
{"id":"lisa-bodei","kind":"person","name":"Lisa Bodei","aka":[],"tldr":"An Italian-trained nuclear medicine doctor who helped develop the lutetium-177 dotatate treatment for neuroendocrine tumours and now leads targeted radionuclide therapy at Memorial Sloan Kettering in New York.","summary":"Lisa Bodei trained in nuclear medicine in Italy and worked at the European Institute of Oncology in Milan, where she ran early phase I-II studies of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) and published long-term toxicity data across hundreds of neuroendocrine tumour patients. She moved to Memorial Sloan Kettering Cancer Center, where she is Director of Targeted Radionuclide Therapy in the Molecular Imaging and Therapy Service, and is a substudy author on the dosimetry component of the pivotal NETTER-1 trial that supported Lutathera's approval.\n\nShe co-authored the joint IAEA/EANM/SNMMI practical guidance on PRRT and is an associate editor of the Journal of Nuclear Medicine. Her current work extends theranostics beyond somatostatin receptors to new targets such as DLL3 in neuroendocrine and small-cell lung cancer.","asOf":"2026-09-22","links":[{"label":"MSK doctor profile","url":"https://www.mskcc.org/cancer-care/doctors/lisa-bodei"},{"label":"NETTER-1 dosimetry substudy, JNM 2025","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11876735/"}],"tags":["neuroendocrine","PRRT","clinician"],"related":["lutathera","netter-1","prrt","mskcc","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Attending Physician and Director of Targeted Radionuclide Therapy, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center; Professor of Radiology, Weill Cornell Medical College","specialisms":["peptide receptor radionuclide therapy (PRRT)","dosimetry","neuroendocrine tumour theranostics"],"profiles":[{"label":"MSK doctor profile","url":"https://www.mskcc.org/cancer-care/doctors/lisa-bodei"},{"label":"NETRF board of advisors biography","url":"https://netrf.org/about-netrf/board-of-advisors/"}],"papers":[{"title":"The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2013,"doi":"10.1007/s00259-012-2330-6"},{"title":"Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II study","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2011,"doi":"10.1007/s00259-011-1902-1"},{"title":"Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced Midgut Neuroendocrine Tumors: Results from a Substudy of the Phase III NETTER-1 Trial","journal":"Journal of Nuclear Medicine","year":2025,"doi":"10.2967/jnumed.124.268903"},{"title":"Radiotheranostics in oncology: current challenges and emerging opportunities","journal":"Nature Reviews Clinical Oncology","year":2022,"doi":"10.1038/s41571-022-00652-y"}],"route":"/people/lisa-bodei/"}
{"id":"matthias-eiber","kind":"person","name":"Matthias Eiber","aka":[],"tldr":"A German nuclear medicine physician whose 2015 study of gallium-68 PSMA PET scanning for prostate cancer became one of the most-cited papers in the field, and who now leads theranostics research in Munich.","summary":"Matthias Eiber led the seminal 2015 Journal of Nuclear Medicine study evaluating hybrid 68Ga-PSMA-11 PET/CT in 248 patients with biochemical recurrence after radical prostatectomy, a paper that is credited with driving global adoption of PSMA PET imaging. Working within Markus Schwaiger's department at TUM's Klinikum rechts der Isar, he subsequently helped develop and validate PSMA-I&T and compared 68Ga-PSMA-11 against 18F-PSMA-1007.\n\nHe leads the Theranostics Section at his department (since 2020) and is a co-author of the PROMISE miTNM framework for standardised PSMA-PET reporting and of RECIP 1.0, a framework for assessing radiographic response to PSMA-targeted radioligand therapy. He continues to publish extensively on PSMA PET-guided radioligand therapy dosimetry and outcome prediction, including work linked to the PSMAddition trial.","asOf":"2026-09-22","links":[{"label":"TUM CV page","url":"https://nuklearmedizin.mri.tum.de/de/lebenslauf-prof-dr-med-matthias-eiber"},{"label":"68Ga-PSMA-11 PET/CT biochemical recurrence study, JNM 2015","url":"https://jnm.snmjournals.org/content/56/5/668"}],"tags":["PSMA","PET","clinician"],"related":["ga68-psma-11","psma-pet","tum-munich","psmaddition","f-18","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor and Head of the Theranostics Section, Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich","institutionId":"tum-munich","specialisms":["PSMA PET","PSMA radioligand therapy","prostate cancer imaging biomarkers"],"profiles":[{"label":"TUM Klinik für Nuklearmedizin CV (German)","url":"https://nuklearmedizin.mri.tum.de/de/lebenslauf-prof-dr-med-matthias-eiber"},{"label":"TUM research portal (FIS)","url":"https://portal.fis.tum.de/en/persons/matthias-eiber/"}],"papers":[{"title":"Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy","journal":"Journal of Nuclear Medicine","year":2015,"doi":"10.2967/jnumed.115.154153"},{"title":"Matched-Pair Comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: Frequency of Pitfalls and Detection Efficacy in Biochemical Recurrence After Radical Prostatectomy","journal":"Journal of Nuclear Medicine","year":2020,"doi":"10.2967/jnumed.119.229187"},{"title":"Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT","journal":"Journal of Nuclear Medicine","year":2018,"doi":"10.2967/jnumed.117.198119"},{"title":"[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial","journal":"The Lancet","year":2026,"url":"https://portal.fis.tum.de/en/organisations/department-of-nuclear-medicine/"}],"route":"/people/matthias-eiber/"}
{"id":"stefano-fanti","kind":"person","name":"Stefano Fanti","aka":[],"tldr":"An Italian nuclear medicine professor who built one of Europe's busiest PET centres in Bologna and co-writes the international guidelines that tell doctors when and how to use PSMA PET scans in prostate cancer.","summary":"Stefano Fanti has directed the Nuclear Medicine Division and PET Unit at the Policlinico Sant'Orsola in Bologna since the early 2000s, building it into one of the most active European centres for non-FDG PET tracers, and is now also Vice Rector for Research at the University of Bologna. He co-authored the first standardised interpretive framework for PSMA-ligand PET (2017) and is a repeat co-author of the EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guidelines that define the clinical role of PSMA PET in staging and restaging.\n\nHe has proposed and co-authored consensus criteria for assessing PSMA PET response to systemic therapy (the PSMA PET progression criteria, and consensus statements on PSMA PET/CT response assessment), and is a co-author of the EANM/SNMMI PSMA PET/CT procedure guideline versions 1.0 and 2.0. His work bridges the clinical and regulatory sides of PSMA imaging standardisation across Europe and the US.","asOf":"2026-09-22","links":[{"label":"University of Bologna profile","url":"https://www.unibo.it/sitoweb/s.fanti/en"},{"label":"Consensus statements on PSMA PET/CT response, EJNMMI 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7835167/"}],"tags":["PSMA","guidelines","clinician"],"related":["psma-pet","ga68-psma-11","sant-orsola-bologna"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Full Professor of Diagnostic Imaging and Director of Nuclear Medicine, University of Bologna / Policlinico Sant'Orsola; Vice Rector for Research, University of Bologna","institutionId":"sant-orsola-bologna","specialisms":["PSMA PET","PET response criteria","guideline development"],"profiles":[{"label":"University of Bologna staff page","url":"https://www.unibo.it/sitoweb/s.fanti/en"},{"label":"University of Bologna CV (English)","url":"https://www.unibo.it/sitoweb/s.fanti/cv-en"},{"label":"Google Scholar","url":"https://scholar.google.com/citations?user=ZB07UFEAAAAJ&hl=en"}],"papers":[{"title":"Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2021,"doi":"10.1007/s00259-020-04934-4"},{"title":"Proposal for systemic-therapy response-assessment criteria at the time of PSMA PET/CT imaging: the PSMA PET progression criteria","journal":"Journal of Nuclear Medicine","year":2020,"doi":"10.2967/jnumed.119.233817"},{"title":"PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023,"doi":"10.1007/s00259-022-06089-w"}],"route":"/people/stefano-fanti/"}
{"id":"wolfgang-fendler","kind":"person","name":"Wolfgang P. Fendler","aka":[],"tldr":"A German nuclear medicine doctor at Essen who helped design a scoring system, RECIP, for reading follow-up PSMA scans in prostate cancer patients on lutetium therapy, and who co-writes the field's international imaging guidelines.","summary":"Wolfgang Fendler is vice chair (deputy director, under Ken Herrmann) and head of translational oncology at the University Hospital Essen's Department of Nuclear Medicine, and a member of the German Cancer Consortium (DKTK). He is first or senior author on a series of studies validating Response Evaluation Criteria in PSMA-PET/CT (RECIP 1.0), a framework for reading follow-up PSMA PET scans in men on 177Lu-PSMA radioligand therapy, and co-authored the EANM/SNMMI joint procedure guidelines for both PSMA PET/CT and 177Lu-PSMA radioligand therapy.\n\nHis research also covers real-world outcomes of extended and rechallenge 177Lu-PSMA-617 therapy in metastatic castration-resistant prostate cancer, and he received the EAU Prostate Cancer Research Award in 2021 for his work relating PSMA-ligand PET findings to clinical outcomes in non-metastatic castration-resistant prostate cancer.","asOf":"2026-09-22","links":[{"label":"Essen Klinik für Nuklearmedizin, oncology team page","url":"https://nuklearmedizin.uk-essen.de/onkologie/"},{"label":"RECIP 1.0, Radiology / RECIP criteria collaboration site","url":"https://recip-criteria.com/"}],"tags":["PSMA","response criteria","clinician"],"related":["essen-wtz","psma-pet","lu177-radioligand-therapy","ken-herrmann","matthias-eiber","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor and Vice Chair (deputy director), Department of Nuclear Medicine, University Hospital Essen / University of Duisburg-Essen","institutionId":"essen-wtz","specialisms":["PSMA PET response assessment","radioligand therapy trials","German Cancer Consortium (DKTK) translational research"],"profiles":[{"label":"Essen nuclear medicine department page","url":"https://nuklearmedizin.uk-essen.de/onkologie/"}],"papers":[{"title":"Novel framework for treatment response evaluation using PSMA PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP 1.0): an international multicenter study","journal":"Journal of Nuclear Medicine","year":2022,"url":"https://recip-criteria.com/"},{"title":"Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023,"doi":"10.1007/s00259-023-06255-8"},{"title":"PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023,"doi":"10.1007/s00259-022-06089-w"}],"route":"/people/wolfgang-fendler/"}
{"id":"phillip-kuo","kind":"person","name":"Phillip H. Kuo","aka":[],"tldr":"A nuclear medicine physician who helped write the eligibility scans used to select prostate cancer patients for the VISION trial of lutetium-177 PSMA-617, and who also sets national standards for brain PET scans used in Alzheimer's disease.","summary":"Phillip Kuo spent a decade as Chief of Nuclear Medicine at the University of Arizona before moving in 2024 to City of Hope Cancer Center in Duarte, California, where he is Division Chief of Nuclear Medicine and Director of Theranostics. He co-authored the explanation of the PSMA PET/CT selection criteria used in the pivotal VISION trial of 177Lu-PSMA-617, and has contributed to SNMMI appropriate-use-criteria panels for both PSMA PET and 177Lu-PSMA-617 radioligand therapy.\n\nHe also works in neurodegeneration imaging, serving on the Alzheimer's Association/SNMMI workgroup that issues updated appropriate use criteria for amyloid and tau PET, and as a co-author of the SNMMI/EANM procedure standard for brain FDG PET. This dual focus on prostate cancer theranostics and dementia imaging makes him one of relatively few nuclear medicine leaders bridging oncologic and neurologic molecular imaging standards.","asOf":"2026-09-22","links":[{"label":"City of Hope profile","url":"https://www.cityofhope.org/phillip-kuo"},{"label":"Why we did what we did, JNM 2022","url":"https://jnm.snmjournals.org/content/63/6/816"}],"tags":["PSMA","theranostics","brain PET","clinician"],"related":["vision","pluvicto","psma-pet","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor and Division Chief of Nuclear Medicine and Director of Theranostics, Department of Diagnostic Radiology, City of Hope Cancer Center (since 2024; previously Chief of Nuclear Medicine, University of Arizona, 2014-2024)","specialisms":["PSMA PET patient selection","amyloid and tau brain PET","appropriate use criteria"],"profiles":[{"label":"City of Hope profile","url":"https://www.cityofhope.org/phillip-kuo"}],"papers":[{"title":"Why We Did What We Did: PSMA-PET/CT Selection Criteria for the VISION Trial","journal":"Journal of Nuclear Medicine","year":2022,"doi":"10.2967/jnumed.121.263638"},{"title":"Updated Appropriate Use Criteria for Amyloid and Tau PET: A Report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup","journal":"Journal of Nuclear Medicine","year":2025,"doi":"10.2967/jnumed.124.268756"},{"title":"SNMMI Procedure Standard/EANM Practice Guideline for Brain [18F]FDG PET Imaging, Version 2.0","journal":"Journal of Nuclear Medicine","year":2025}],"route":"/people/phillip-kuo/"}
{"id":"heiko-schoder","kind":"person","name":"Heiko Schöder","aka":["Heiko Schoder"],"tldr":"A nuclear medicine doctor who runs the molecular imaging service at Memorial Sloan Kettering and has spent years studying how PET scans taken partway through chemotherapy for lymphoma can predict which patients need more or less treatment.","summary":"Heiko Schöder has been Chief of the Molecular Imaging and Therapy Service in the Department of Radiology at Memorial Sloan Kettering Cancer Center since 2018, after joining MSK in 2001 and rising through clinical director and deputy chief roles. His research programme centres on interim and end-of-treatment FDG PET as a prognostic and response-adapted-therapy tool in Hodgkin and non-Hodgkin lymphoma, including analyses of the CALGB 50303 and SWOG S0816 trials and pooled analyses of interim-PET Deauville scoring in advanced Hodgkin lymphoma.\n\nHe is a regular co-author of the SNMMI Highlights Lectures summarising annual advances in oncologic PET and therapy, and has published on theranostics more broadly, including a widely cited review of radiotheranostics challenges and opportunities with Lisa Bodei, Ken Herrmann and colleagues. His clinical practice also spans cardiac and head-and-neck cancer nuclear imaging.","asOf":"2026-09-22","links":[{"label":"MSK doctor profile","url":"https://www.mskcc.org/cancer-care/doctors/heiko-schoder"},{"label":"CALGB 50303 interim-PET analysis, Blood 2020","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7316220/"}],"tags":["lymphoma","FDG PET","clinician"],"related":["mskcc","lisa-bodei","rathl","fdg-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Chief, Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center; Professor of Radiology, Weill Cornell Medical College","institutionId":"mskcc","specialisms":["FDG PET in lymphoma","response-adapted therapy","theranostics"],"profiles":[{"label":"MSK doctor profile","url":"https://www.mskcc.org/cancer-care/doctors/heiko-schoder"}],"papers":[{"title":"Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial","journal":"Blood","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7316220/"},{"title":"Radiotheranostics in oncology: current challenges and emerging opportunities","journal":"Nature Reviews Clinical Oncology","year":2022,"doi":"10.1038/s41571-022-00652-y"},{"title":"2022 SNMMI Highlights Lecture: Oncology and Therapy, Part 1","journal":"Journal of Nuclear Medicine","year":2022,"url":"https://pubmed.ncbi.nlm.nih.gov/36456112/"}],"route":"/people/heiko-schoder/"}
{"id":"andrei-iagaru","kind":"person","name":"Andrei Iagaru","aka":[],"tldr":"A Stanford nuclear medicine professor who led the division for a decade and has published widely on new PET tracers, from FAPI scans of fibrosis-related proteins to whole-body PET scanners that image the entire body at once.","summary":"Andrei Iagaru joined Stanford in 2007 and served as Chief of the Division of Nuclear Medicine and Molecular Imaging from 2016 (co-chief from 2011); Stanford's faculty listing as of September 2026 names Erin Grady as interim division chief, indicating a leadership transition, while Iagaru continues as Professor of Radiology. He has authored or co-authored more than 200 peer-reviewed papers spanning 68Ga-PSMA-11 and 18F-DCFPyL PET for prostate cancer, gastrin-releasing peptide receptor (GRPR) imaging, and fibroblast activation protein inhibitor (FAPI) PET.\n\nHe has been a prominent voice in the debate over whether FAPI PET will replace FDG PET in oncologic staging, arguing for a complementary rather than replacement role, and is active in total-body and long-axial-field-of-view PET research and international PET/MRI consensus guideline efforts with EANM, SNMMI and ISMRM.","asOf":"2026-09-22","links":[{"label":"Stanford Profiles","url":"https://cap.stanford.edu/profiles/frdActionServlet?choiceId=printerprofile&profileversion=full&profileId=8156"},{"label":"Stanford Nuclear Medicine faculty page","url":"https://med.stanford.edu/nuclearmedicine/people/faculty.html"}],"tags":["PSMA","FAPI","total-body PET","clinician"],"related":["fapi-pet","ga68-psma-11","pet-mri","f-18","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Radiology (Nuclear Medicine), Stanford University Medical Center (formerly Chief of the Division of Nuclear Medicine and Molecular Imaging, 2016-2026; Stanford's faculty page as of September 2026 lists Erin Grady, MD, as Interim Division Chief)","specialisms":["FAPI PET","total-body and long-axial-field-of-view PET","PSMA PET"],"profiles":[{"label":"Stanford Profiles CV","url":"https://cap.stanford.edu/profiles/viewCV?facultyId=8156&name=Andrei_Iagaru"},{"label":"Stanford Nuclear Medicine faculty page","url":"https://med.stanford.edu/nuclearmedicine/people/faculty.html"},{"label":"Google Scholar","url":"https://scholar.google.com/citations?user=8RwEbvgAAAAJ&hl=en"}],"papers":[{"title":"Will FAPI PET/CT Replace FDG PET/CT in the Next Decade?-Counterpoint: No, not so fast!","journal":"American Journal of Roentgenology","year":2020,"url":"https://pubmed.ncbi.nlm.nih.gov/33356420/"},{"title":"Gallium 68 PSMA-11 PET/MR imaging in patients with intermediate- or high-risk prostate cancer","journal":"Radiology","year":2018,"url":"https://pubs.rsna.org/doi/10.1148/radiol.2018172232"},{"title":"International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023}],"route":"/people/andrei-iagaru/"}
{"id":"delphine-chen","kind":"person","name":"Delphine L. Chen","aka":[],"tldr":"A Seattle-based nuclear medicine physician-scientist who ran the first human trial of a PET tracer that shows whether a tumour will respond to PARP-inhibitor drugs, and who now directs nuclear medicine and molecular imaging therapy at the Fred Hutchinson Cancer Center.","summary":"Delphine Chen holds the Wil B. Nelp, MD Endowed Professorship in Nuclear Medicine at the University of Washington and directs Molecular Imaging and Therapy at Fred Hutchinson Cancer Center, a role she has held since 2019; from January 2026 she also became Clinical Research Director for Radiology at Fred Hutch. She was principal investigator on the first-in-human trial of 18F-fluorthanatrace (18F-FTT), a PET tracer for imaging PARP-1 expression to help predict response to PARP-inhibitor drugs, developed with a patent held by Washington University.\n\nHer clinical practice covers the full range of oncologic PET and nuclear medicine therapies, and she has led trials using 68Ga-PSMA-11 PET to predict prostate cancer response to standard therapies. She currently serves SNMMI as President of the Center for Molecular Imaging, Innovation, and Translation.","asOf":"2026-09-22","links":[{"label":"Fred Hutch faculty profile","url":"https://www.fredhutch.org/en/faculty-lab-directory/chen-delphine.html"},{"label":"UW Radiology profile","url":"https://rad.uw.edu/people/dlchen7"}],"tags":["PARP PET","clinician-scientist"],"related":["parp-pet","parp","snmmi","f-18","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor, Clinical Research Division, Fred Hutchinson Cancer Center; Professor of Radiology, University of Washington; Clinical Research Director for Radiology, Fred Hutch (from January 2026; Director of Molecular Imaging and Therapy, Fred Hutch, since 2019)","specialisms":["PARP PET imaging","PET methods development","radioligand therapy multidisciplinary care"],"profiles":[{"label":"Fred Hutch faculty profile","url":"https://www.fredhutch.org/en/faculty-lab-directory/chen-delphine.html"},{"label":"UW Radiology profile","url":"https://rad.uw.edu/people/dlchen7"}],"papers":[{"title":"PET Imaging of PARP Expression Using 18F-Olaparib","journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.118.219733"},{"title":"A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1","journal":"Radiology","year":2022,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8830434/"},{"title":"Pilot study: PARP1 imaging in advanced prostate cancer","journal":"Molecular Imaging and Biology","year":2022,"url":"https://digitalcommons.wustl.edu/oa_4/3816"}],"route":"/people/delphine-chen/"}
{"id":"erik-mittra","kind":"person","name":"Erik S. Mittra","aka":[],"tldr":"A Stanford-trained nuclear medicine doctor who leads the theranostics programme at Oregon Health & Science University and treats neuroendocrine tumour patients with radioactive peptide therapy.","summary":"Erik Mittra trained through the MD/PhD programme at Stony Brook University and completed nuclear medicine residency and PET/CT fellowship at Stanford, where he was faculty for eight years before joining Oregon Health & Science University (OHSU) in 2018. He is now Chief of Nuclear Medicine and Molecular Imaging and Director of Radiopharmaceutical Therapeutics at OHSU, running its multidisciplinary neuroendocrine tumour treatment programme.\n\nHis research focuses on peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, including as a co-author on the substudy dosimetry analysis of the pivotal NETTER-1 trial, and on 90Y radioembolisation dosimetry using fused MAA-SPECT imaging. He has published extensively on FDG and NaF PET applications in oncology dating back to his Stanford years.","asOf":"2026-09-22","links":[{"label":"OHSU provider profile","url":"https://www.ohsu.edu/providers/erik-s-mittra-md-phd"},{"label":"NETRF specialist profile","url":"https://netrf.org/specialist/erik-mittra-md-phd/"}],"tags":["neuroendocrine","PRRT","clinician"],"related":["lutathera","netter-1","radioembolisation-tare","prrt","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Professor of Diagnostic Radiology; Chief, Nuclear Medicine and Molecular Imaging; Director, Radiopharmaceutical Therapeutics, Oregon Health & Science University","specialisms":["neuroendocrine tumour theranostics","PRRT","radioembolisation dosimetry"],"profiles":[{"label":"OHSU provider profile","url":"https://www.ohsu.edu/providers/erik-s-mittra-md-phd"}],"papers":[{"title":"Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced Midgut Neuroendocrine Tumors: Results from a Substudy of the Phase III NETTER-1 Trial","journal":"Journal of Nuclear Medicine","year":2025,"doi":"10.2967/jnumed.124.268903"},{"title":"Prognostic Utility of 90Y Radioembolization Dosimetry Based on Fusion 99mTc-Macroaggregated Albumin-99mTc-Sulfur Colloid SPECT","journal":"Journal of Nuclear Medicine","year":2013,"url":"https://pubmed.ncbi.nlm.nih.gov/24136932/"}],"route":"/people/erik-mittra/"}
{"id":"amir-iravani","kind":"person","name":"Amir Iravani","aka":[],"tldr":"A nuclear medicine physician-scientist who worked on the practice-changing TheraP and LuPSMA trials in Australia and has moved through Fred Hutchinson to UCLA in 2026 to build a new hospital theranostics programme.","summary":"Amir Iravani trained at Melbourne's Peter MacCallum Cancer Centre, where he was a co-investigator on the LuPSMA phase 2 trial and the TheraP randomised phase 2 trial (177Lu-PSMA-617 versus cabazitaxel), including work on PSMA and FDG PET as predictive and prognostic biomarkers. He later became Theranostics Clinical Director at Fred Hutchinson Cancer Center and Associate Professor of Radiology at the University of Washington, where he studied how PSMA/FDG dual-tracer selection criteria (TheraP-style versus VISION-style) affect outcomes with 177Lu-PSMA-617.\n\nIn July 2026 he joined UCLA Health as Director of the Theranostics Program and Vice Chair of Clinical Research in the newly established Department of Nuclear Medicine and Theranostics, tasked with expanding clinical trials and research collaborations in precision radiopharmaceutical care.","asOf":"2026-09-22","links":[{"label":"UCLA Health news release, September 2026","url":"https://www.uclahealth.org/news/release/nuclear-medicine-physician-scientist-dr-amir-iravani-joins"},{"label":"Becker's Hospital Review coverage","url":"https://www.beckershospitalreview.com/radiology/ucla-health-taps-fred-hutch-theranostics-leader/"}],"tags":["PSMA","theranostics","clinician"],"related":["therap","pluvicto","ucla-jonsson","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Associate Professor and Vice Chair of Clinical Research, Director of the Theranostics Program, Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine at UCLA (from July 2026; previously Theranostics Clinical Director, Fred Hutchinson Cancer Center, and Associate Professor of Radiology, University of Washington, 2022-2026)","specialisms":["PSMA radioligand therapy trials","dosimetry","dual-tracer (PSMA/FDG) patient selection"],"profiles":[{"label":"UW Radiology profile (2022-2026)","url":"https://rad.uw.edu/people/airavani"},{"label":"UCLA Health announcement, September 2026","url":"https://www.uclahealth.org/news/release/nuclear-medicine-physician-scientist-dr-amir-iravani-joins"}],"papers":[{"title":"[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial","journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00237-3"},{"title":"[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study","journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30198-0"},{"title":"PET-Based TheraP Eligibility and Outcomes of VISION-Eligible Patients with Metastatic Castration-Resistant Prostate Cancer Who Received 177Lu-PSMA-617","journal":"Journal of Nuclear Medicine","year":2025,"doi":"10.2967/jnumed.124.268578"}],"route":"/people/amir-iravani/"}
{"id":"rodney-hicks","kind":"person","name":"Rodney J. Hicks","aka":[],"tldr":"An Australian nuclear medicine pioneer who built Peter MacCallum Cancer Centre's molecular imaging and therapy service into a world-renowned unit over three decades, and now runs an independent theranostics centre in Melbourne.","summary":"Rodney Hicks directed cancer imaging and later the Centre for Molecular Imaging and Therapeutic Nuclear Medicine at Melbourne's Peter MacCallum Cancer Centre for around three decades, building a nuclear medicine service that helped pioneer clinical PET/CT in Australia and later 177Lu-PSMA-617 radioligand therapy. He was a senior author on the single-centre LuPSMA phase 2 trial and contributed to the proPSMA randomised trial of PSMA PET-CT for staging high-risk prostate cancer, and to methods for single-time-point SPECT/CT dosimetry of 177Lu-PSMA-617 therapy.\n\nAfter leaving Peter Mac in 2021, he founded the Melbourne Theranostic Innovation Centre (MTIC), where he is Executive Chairman and Chief Medical Officer, delivering theranostics clinical and research services in partnership with industry, while retaining a professorial appointment at the University of Melbourne.","asOf":"2026-09-22","links":[{"label":"Melbourne Theranostic Innovation Centre","url":"https://www.mtic.net.au/mtic-team/professor-rodney-hicks"},{"label":"proPSMA trial, The Lancet 2020","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30314-7/fulltext"}],"tags":["PSMA","theranostics","clinician"],"related":["propsma","paper-propsma-hofman-lancet-2020","pluvicto","peter-mac","amir-iravani","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Founder, Executive Chairman and Chief Medical Officer, Melbourne Theranostic Innovation Centre; Professor of Medicine, University of Melbourne (previously Director, Centre for Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, until 2021)","specialisms":["theranostics programme building","neuroendocrine tumour PET","PSMA radioligand therapy dosimetry"],"profiles":[{"label":"Melbourne Theranostic Innovation Centre team page","url":"https://www.mtic.net.au/mtic-team/professor-rodney-hicks"},{"label":"Discovery Medicine biography","url":"https://www.discoverymedicine.com/Rodney-J-Hicks/about/"}],"papers":[{"title":"[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study","journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30198-0"},{"title":"Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study","journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7"},{"title":"Radiation Dosimetry in 177Lu-PSMA-617 Therapy Using a Single Posttreatment SPECT/CT Scan: A Novel Methodology to Generate Time- and Tissue-Specific Dose Factors","journal":"Journal of Nuclear Medicine","year":2020,"doi":"10.2967/jnumed.119.233411"}],"route":"/people/rodney-hicks/"}
{"id":"dale-bailey","kind":"person","name":"Dale L. Bailey","aka":[],"tldr":"An Australian medical physicist who helped prove that SPECT scans, not just PET scans, can measure exact amounts of radioactivity in the body, which underpins accurate dosing of radioactive cancer treatments.","summary":"Dale Bailey has worked in nuclear medicine medical physics for more than 35 years and holds joint appointments as Principal Medical Physics Specialist at Sydney's Royal North Shore Hospital and Professor in the Faculty of Medicine and Health at the University of Sydney. With Kathy Willowson, he authored widely cited reviews establishing quantitative SPECT/CT as a technique for measuring absolute radioactivity concentration (kBq/mL) comparable in principle to quantitative PET, work that underlies modern post-therapy dosimetry for lutetium-177 and other therapeutic radionuclides.\n\nHe directs the Sydney Vital Northern Translational Cancer Research Centre and has developed methodology for calibrating and validating PET and SPECT scanners for quantitative multicentre clinical trials using non-standard radionuclides such as iodine-124 and iodine-131. His methods work is closely aligned with, and has fed into, the EANM/SNMMI physics and dosimetry standards used across the radiopharmaceutical field.","asOf":"2026-09-22","links":[{"label":"University of Sydney CV","url":"https://www.sydney.edu.au/AcademicProfiles/profile/resource?urlid=dale.bailey&type=cv"},{"label":"Quantitative SPECT/CT review, EJNMMI 2014","url":"https://pubmed.ncbi.nlm.nih.gov/24037503/"}],"tags":["physics","dosimetry","SPECT"],"related":["spect-ct","radioligand-dosimetry","in-vivo-dosimetry","i-124","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Principal Medical Physics Specialist, Department of Nuclear Medicine, Royal North Shore Hospital, Sydney; Professor, Faculty of Medicine and Health, University of Sydney","specialisms":["quantitative SPECT/CT","radionuclide dosimetry","PET/SPECT camera calibration"],"profiles":[{"label":"University of Sydney academic profile / CV","url":"https://www.sydney.edu.au/AcademicProfiles/profile/resource?urlid=dale.bailey&type=cv"},{"label":"Google Scholar","url":"https://scholar.google.com.au/citations?user=0Mq8GUMAAAAJ&hl=en"}],"papers":[{"title":"An evidence-based review of quantitative SPECT imaging and potential clinical applications","journal":"Journal of Nuclear Medicine","year":2013,"doi":"10.2967/jnumed.112.111476"},{"title":"Quantitative SPECT/CT: SPECT joins PET as a quantitative imaging modality","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2014,"doi":"10.1007/s00259-013-2542-4"},{"title":"A Method for Validating PET and SPECT Cameras for Quantitative Clinical Imaging Trials Using Novel Radionuclides","journal":"Journal of Nuclear Medicine","year":2025,"doi":"10.2967/jnumed.124.268578"}],"route":"/people/dale-bailey/"}
{"id":"michael-lassmann","kind":"person","name":"Michael Lassmann","aka":[],"tldr":"A German medical physicist who has led the physics section of Würzburg's nuclear medicine department for three decades and helped set the international standards used to calculate radiation doses from radioactive cancer treatments.","summary":"Michael Lassmann has worked as a medical physics expert in the Department of Nuclear Medicine at University Hospital Würzburg since 1988, was appointed head of the department's physics section in 1994, and holds a full professorship on the university's medical faculty. Between 2001 and 2008 he chaired the EANM Dosimetry Committee and continues to serve as a senior advisor to it; in 2017 he received the SNMMI Loevinger-Berman Award, nuclear medicine's leading dosimetry prize.\n\nHis research spans internal dosimetry for peptide receptor radionuclide therapy and radioiodine therapy, bone-marrow dosimetry methods, and biodosimetry for radiation protection. He is a co-author of the EANM/SNMMI joint procedure guideline for 177Lu-labelled PSMA-targeted radioligand therapy and of the PSMA-I&T theranostic first-in-human studies, and has continued this line of work through his successor Johannes Tran-Gia's Heisenberg professorship in multimodal imaging and theranostics at Würzburg.","asOf":"2026-09-22","links":[{"label":"University Hospital Würzburg profile","url":"https://www.ukw.de/nuklearmedizin/team/nuklearmedizin-detail/name/lassmann-michael/"},{"label":"Lassmann receives 2017 Loevinger-Berman Award","url":"https://jnm.snmjournals.org/content/jnumed/58/8/14N.full.pdf"}],"tags":["physics","dosimetry"],"related":["radioligand-dosimetry","prrt","lu177-radioligand-therapy","richard-baum","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"role":"Head of Medical Physics, Department of Nuclear Medicine, University Hospital Würzburg","specialisms":["internal dosimetry","radiation protection","PRRT and radioiodine dosimetry"],"profiles":[{"label":"University Hospital Würzburg staff page (German)","url":"https://www.ukw.de/nuklearmedizin/team/nuklearmedizin-detail/name/lassmann-michael/"},{"label":"ORCID","url":"https://orcid.org/0000-0002-2556-1977"},{"label":"DFG GEPRIS researcher profile","url":"https://gepris.dfg.de/gepris/person/15130779"}],"papers":[{"title":"Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2023,"doi":"10.1007/s00259-023-06255-8"},{"title":"68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies","journal":"Journal of Nuclear Medicine","year":2015,"doi":"10.2967/jnumed.115.158550"}],"orcid":"0000-0002-2556-1977","route":"/people/michael-lassmann/"}
{"id":"alpha-therapy-roadmap","kind":"roadmap","name":"Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline","aka":[],"tldr":"Alpha particles carry much more energy over a much shorter distance than the beta particles used in Lutathera and Pluvicto, so they can be more powerful against small clusters of cancer cells. The first alpha drug was approved in 2013; a wave of alpha versions of existing beta drugs is now in late-stage testing, and the isotopes are still scarce.","summary":"Alpha-particle therapy began clinically with radium-223 dichloride, approved by the FDA on 15 May 2013 for bone metastases in prostate cancer after the ALSYMPCA trial, though radium-223 is a bone-seeker rather than a targeted radioligand. The targeted-alpha era proper starts with Kratochwil and colleagues at Heidelberg and the Joint Research Centre Karlsruhe, who treated the first patients with 225Ac-PSMA-617 in 2014 and reported complete responses in two heavily pretreated men with metastatic castration-resistant prostate cancer in 2016, followed by empirical dose-finding in a larger series in 2017.\n\nThat compassionate-use experience seeded a pipeline of sponsor-run trials repeating the beta-to-alpha substitution across targets: 225Ac-DOTATATE (RYZ101, RayzeBio/BMS) in the ACTION-1 trial for neuroendocrine tumours progressing after 177Lu-DOTATATE; 225Ac-PSMA-I&T (FPI-2265, Fusion Pharmaceuticals/AstraZeneca) in AlphaBreak for prostate cancer after 177Lu-PSMA; 225Ac-PSMA-617 (AAA817, Novartis) in a phase 3 programme; and 212Pb-DOTAMTATE (AlphaMedix, RadioMedix/Orano Med/Sanofi), whose phase 2 ALPHAMEDIX-02 study reported that it met all primary efficacy endpoints in October 2025. Every one of these programmes is capacity-constrained: actinium-225 in particular is scarce, and lead-212 and actinium-225 production are both being scaled by companies such as TerraPower Isotopes and Orano Med.\n\nThe unresolved questions are whether alpha activity will translate into a survival benefit large enough for approval once the phase 3 readouts arrive (2026-2028 on current registry estimates), whether the added myelotoxicity and xerostomia seen in compassionate-use series are tolerable at scale, and whether supply can grow fast enough to support first-line or earlier-line use rather than remaining a last-resort option after beta radioligand therapy fails.","asOf":"2026-09-22","links":[{"label":"FDA: Alsympca (radium-223 dichloride) approval, May 2013","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203971Orig1s000TOC.cfm"},{"label":"Kratochwil et al., 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy (J Nucl Med 2016)","url":"https://pubmed.ncbi.nlm.nih.gov/27390158/"},{"label":"RayzeBio/ClinicalTrials.gov: ACTION-1 (NCT05477576)","url":"https://clinicaltrials.gov/study/NCT05477576"},{"label":"Sanofi: AlphaMedix (212Pb-DOTAMTATE) ALPHAMEDIX-02 phase 2 results, October 2025","url":"https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053"},{"label":"TerraPower Isotopes: Bellwether Laboratory groundbreaking, May 2026","url":"https://www.terrapower.com/TerraPower-Isotopes-Breaks-Ground-on-Worlds-Largest-Actinium-225-Manufacturing-Facility-in-Philadelphia"}],"tags":[],"related":["lu-177","ac-225","ra-223","pb-212"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","actinium-225-supply","radioligand-therapy","prrt"],"targets":[],"drugs":["radium-223","ryz101","fpi-2265","ac225-psma","alphamedix"],"companies":["rayzebio","fusion-pharma","novartis","orano-med","radiomedix","terrapower-isotopes"],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca","action-1","alphabreak","alphamedix-02"],"people":["clemens-kratochwil","uwe-haberkorn"],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"2013","title":"Radium-223: the first alpha emitter approved","description":"The FDA approves radium-223 dichloride on 15 May 2013 for symptomatic bone metastases in castration-resistant prostate cancer, based on the ALSYMPCA trial (median overall survival 14.9 vs 11.3 months). Radium-223 is a bone-seeking calcium mimetic rather than a receptor-targeted ligand, but it establishes that an alpha emitter can be given systemically and safely.","refs":["radium-223","alsympca","paper-alsympca-radium-223-nejm-2013"],"status":"historic"},{"era":"2014-2017","title":"First-in-human targeted alpha therapy: 225Ac-PSMA-617","description":"Clinical investigation of 225Ac-PSMA-617 begins in 2014 at Heidelberg University Hospital with the Joint Research Centre Karlsruhe. Kratochwil et al. report complete biochemical and imaging responses in two heavily pretreated men with mCRPC in 2016 (J Nucl Med), then empirical dose-finding (100 kBq/kg every 8 weeks) in a larger series in 2017, establishing the first targeted-alpha treatment protocol in humans.","refs":["clemens-kratochwil","uwe-haberkorn"],"status":"historic"},{"era":"2018-2023","title":"Sponsor-run alpha programmes multiply","description":"Compassionate-use experience is followed by company-sponsored trials repeating the beta-to-alpha substitution across targets and companies: RYZ101 (225Ac-DOTATATE) enters ACTION-1 for GEP-NETs progressing after 177Lu-SSA therapy; FPI-2265 (225Ac-PSMA-I&T) enters AlphaBreak for mCRPC after 177Lu-PSMA; Novartis begins a phase 3 programme for AAA817 (225Ac-PSMA-617); and RadioMedix/Orano Med complete enrolment of the phase 2 ALPHAMEDIX-02 trial of 212Pb-DOTAMTATE in 2023.","refs":["action-1","alphabreak","alphamedix-02","rayzebio","fusion-pharma","novartis","orano-med","radiomedix"],"status":"historic"},{"era":"2024-2026","title":"Supply scales and the first phase 2 readouts land","description":"TerraPower Isotopes announces it is producing actinium-225 at commercial scale via weekly production runs from October 2024. 212Pb-DOTAMTATE receives FDA Breakthrough Therapy designation in 2024, and the ALPHAMEDIX-02 phase 2 study reports in October 2025 that it met all primary efficacy endpoints (ORR 60% in PRRT-naive patients), the first positive alpha-PRRT phase 2 readout in neuroendocrine tumours.","refs":["terrapower-isotopes","alphamedix-02","orano-med"],"status":"current"},{"era":"2026-2029","title":"Phase 3 readouts and a step-change in actinium-225 capacity","description":"ACTION-1, AlphaBreak and the AAA817 phase 3 programme are all due to reach their primary completion dates between late 2026 and 2028, which will determine whether alpha radioligands can be filed for approval as a post-beta salvage option. TerraPower Isotopes breaks ground on a $450m Philadelphia facility in May 2026 intended to increase global actinium-225 production capacity twentyfold.","refs":["action-1","alphabreak","novartis","terrapower-isotopes"],"status":"emerging"},{"era":"2029+","title":"Speculative: alpha therapy in earlier lines","description":"If phase 3 trials read out positively and actinium-225 and lead-212 supply scales as planned, alpha radioligands could move from post-beta salvage into earlier lines, including hormone-sensitive prostate cancer, and combine with PARP inhibitors or immunotherapy. This depends on both an approval and a resolved supply chain; neither is confirmed as of this record's `asOf` date.","refs":["targeted-alpha-therapy","idea-alpha-first-mhspc","idea-alpha-after-adc"],"status":"speculative"}],"watch":[{"item":"ACTION-1 (RYZ101, RayzeBio/BMS) phase 3 primary completion","expected":"Primary Completion (Estimated): 2026-12","source":"https://clinicaltrials.gov/study/NCT05477576","refs":["action-1","rayzebio"]},{"item":"AlphaBreak (FPI-2265, Fusion Pharmaceuticals) phase 2 primary completion","expected":"Estimated Completion: July 23, 2026","source":"https://www.ancora.ai/en/detailsradiopharm/NCT06402331","refs":["alphabreak","fusion-pharma"]},{"item":"AAA817 (Novartis, PSMAcTION, NCT06780670) phase 3 primary completion","expected":"Primary completion date: Jun 27, 2028 (Anticipated)","source":"https://www.allclinicaltrials.com/study/NCT06780670","refs":["novartis"]},{"item":"TerraPower Isotopes' Philadelphia cGMP actinium-225 facility begins production","expected":"Production of cGMP actinium-225 beginning in 2029","source":"https://www.terrapower.com/TerraPower-Isotopes-announces-cGMP-manufacturing-facility","refs":["terrapower-isotopes"]}],"route":"/roadmaps/alpha-therapy-roadmap/"}
{"id":"isotope-supply-roadmap","kind":"roadmap","name":"Isotope supply roadmap: reactor dependence → non-uranium production → accelerator-made actinium","aka":[],"tldr":"The radioactive ingredients that make theranostics work come from a small number of ageing nuclear reactors, generators and accelerators around the world. A shortage anywhere in that chain delays cancer scans and treatments; new non-uranium and accelerator-based production lines are being built to fix that, but they take years and hundreds of millions of dollars.","summary":"For decades the world's molybdenum-99 (the parent of technetium-99m, the workhorse of conventional nuclear medicine) came almost entirely from a handful of ageing research reactors using highly enriched uranium targets, concentrated in Canada, the Netherlands, Belgium, France and South Africa. When Canada's NRU reactor and the Netherlands' HFR both went offline for repairs in 2009-2010, the resulting shortage disrupted nuclear medicine services worldwide and triggered a policy response.\n\nThe US response, formalised in the American Medical Isotope Production Act of 2012, funded non-uranium domestic production. NorthStar Medical Radioisotopes' RadioGenix System, producing molybdenum-99 without highly enriched uranium via neutron capture at the University of Missouri Research Reactor, received FDA approval in February 2018, the first domestic Mo-99 production in roughly three decades. Lutetium-177 demand then rose sharply once Lutathera (2018) and Pluvicto (2022) were approved, straining the same reactor capacity and the enriched ytterbium-176 supply used for no-carrier-added production.\n\nThe newest constraint is actinium-225 for targeted alpha therapy, historically harvested in gram quantities from thorium-229 stockpiles. TerraPower Isotopes announced commercial-scale, weekly actinium-225 production in October 2024 using a natural decay method from thorium-229 recovered from US Department of Energy uranium-233 stocks, and in 2026 broke ground on a $450 million Philadelphia facility intended to increase global capacity twentyfold, with production expected from 2029. Whether reactor, cyclotron and accelerator capacity can keep pace with a growing radioligand pipeline, without a repeat of the 2009-2010 shortage, is the open question this roadmap tracks.","asOf":"2026-09-22","links":[{"label":"DOE/NNSA: FDA approval of domestically-produced, non-uranium based Mo-99, February 2018","url":"https://www.energy.gov/articles/doennsa-partnership-us-healthcare-industry-results-fda-approval-domestically-produced-non"},{"label":"TerraPower Isotopes: reaches market-scale production of actinium-225, October 2024","url":"https://www.terrapower.com/tpi-brings-actinium-225-to-market"},{"label":"TerraPower Isotopes: Bellwether Laboratory groundbreaking, May 2026","url":"https://www.terrapower.com/TerraPower-Isotopes-Breaks-Ground-on-Worlds-Largest-Actinium-225-Manufacturing-Facility-in-Philadelphia"},{"label":"NorthStar: FDA approves additional Mo-99 filling lines, February 2020","url":"https://www.itnonline.com/content/fda-approves-additional-molybdenum-99-mo-99-filling-lines-northstar-medical-radioisotopes"}],"tags":[],"related":["tc-99m","mo-99","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain","actinium-225-supply","cyclotron-isotope-production","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["northstar-medical-radioisotopes","shine-technologies","terrapower-isotopes","orano-med","nordion","ire","ntp-radioisotopes","ansto","nusano"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1960s-2008","title":"Reactor-dependent, HEU-based supply","description":"Global molybdenum-99 supply concentrates in a small number of ageing, mostly HEU-fuelled research reactors (Canada's NRU, the Netherlands' HFR, Belgium's BR2, France's OSIRIS, South Africa's SAFARI-1), each serving large multi-country markets with no domestic US production.","refs":["research-reactor-isotope-production"],"status":"historic"},{"era":"2009-2010","title":"The global Mo-99 shortage","description":"NRU (Chalk River) and HFR both go offline for unplanned repairs at overlapping times, causing a worldwide shortage of molybdenum-99/technetium-99m that disrupts nuclear medicine imaging and prompts a US and international policy response to diversify supply.","refs":["research-reactor-isotope-production"],"status":"historic"},{"era":"2012-2018","title":"Non-HEU domestic Mo-99 production","description":"The American Medical Isotope Production Act (2012) directs the US Department of Energy/NNSA to fund non-HEU Mo-99 production. NorthStar Medical Radioisotopes' RadioGenix System, using neutron-capture production of Mo-99 at the University of Missouri Research Reactor, receives FDA approval on 8 February 2018, the first domestic, non-uranium Mo-99 production since the 1980s.","refs":["northstar-medical-radioisotopes"],"status":"historic"},{"era":"2018-2024","title":"Lutetium-177 demand outpaces capacity","description":"Approvals of Lutathera (2018) and Pluvicto (2022) sharply increase demand for reactor-produced lutetium-177, straining both irradiation capacity and the enriched ytterbium-176 supply used for no-carrier-added Lu-177 production; multiple national reactor operators (ANSTO, IRE, NTP Radioisotopes) expand production lines.","refs":["therapy-isotope-supply-chain","pluvicto","lutathera"],"status":"current"},{"era":"2024-2026","title":"Accelerator-made actinium-225 reaches commercial scale","description":"TerraPower Isotopes announces commercial-scale, weekly actinium-225 production from October 2024, using a natural decay method from thorium-229 recovered from US Department of Energy uranium-233 stockpiles in partnership with Isotek. In March 2026 the company announces a second, much larger facility in Philadelphia.","refs":["terrapower-isotopes","actinium-225-supply"],"status":"current"},{"era":"2026-2029","title":"Building twentyfold actinium-225 capacity","description":"TerraPower Isotopes breaks ground on its $450m Bellwether Laboratory in Philadelphia in May 2026, intended to increase global actinium-225 production capacity twentyfold alongside expansion at its Everett, Washington site; the Pennsylvania state government contributes grant funding. Production is expected to begin in 2029.","refs":["terrapower-isotopes"],"status":"emerging"},{"era":"2029+","title":"Speculative: a resilient, diversified isotope supply","description":"Proposals under discussion include Western enrichment of ytterbium-176 to add a second Lu-177 supplier, a coordinated international reserve and shared schedule for medical isotope reactors, regional radiopharmacy hubs with harmonised transport rules for short-lived isotopes, and a global isotope supply observatory that forecasts shortages before they happen.","refs":["idea-reg-yb176-enrichment-capacity","idea-reg-medical-isotope-reactor-reserve","idea-reg-regional-radiopharmacy-hubs","idea-reg-isotope-supply-observatory","idea-reg-legacy-radium-recovery-ac225"],"status":"speculative"}],"watch":[{"item":"NorthStar RadioGenix expansion and additional Mo-99 filling lines","expected":"FDA approval of two additional Mo-99 filling lines, announced 18 February 2020","source":"https://www.itnonline.com/content/fda-approves-additional-molybdenum-99-mo-99-filling-lines-northstar-medical-radioisotopes","refs":["northstar-medical-radioisotopes"]},{"item":"TerraPower Isotopes' Philadelphia cGMP actinium-225 facility begins production","expected":"Production of cGMP actinium-225 beginning in 2029","source":"https://www.terrapower.com/TerraPower-Isotopes-announces-cGMP-manufacturing-facility","refs":["terrapower-isotopes"]}],"route":"/roadmaps/isotope-supply-roadmap/"}
{"id":"dosimetry-roadmap","kind":"roadmap","name":"Dosimetry roadmap: MIRD schema → fixed dosing → personalised, image-based dose","aka":[],"tldr":"Working out how much radiation a treatment actually delivers to a tumour and to healthy organs, rather than just giving everyone the same fixed amount, could let doctors treat some patients more and some less. The tools to do this patient by patient exist and are used in some specialist centres, but most approved radioligand therapies are still given at one fixed dose to everyone.","summary":"Internal radiation dosimetry has a formal history: the Society of Nuclear Medicine's Medical Internal Radiation Dose (MIRD) Committee was formed in 1965, and its 1968 MIRD Pamphlet No. 1 (Loevinger and Berman) introduced the absorbed-fraction and S-value formalism that still underlies software such as OLINDA. For decades this framework was applied mainly to diagnostic radiopharmaceutical dose estimates rather than to individualising therapy.\n\nPersonalised, image-based dosimetry for peptide receptor radionuclide therapy (PRRT) was developed and tested prospectively from the early 2010s, principally by Swedish groups: Sandström et al. and Garske-Román et al. at Uppsala, and Sundlöv et al. at Lund, used SPECT/CT-based kidney dosimetry to vary the number of 177Lu-DOTATATE cycles per patient up to a fixed renal biologically effective dose (27 Gy, with a 40 Gy option in low-risk patients) rather than a fixed four-cycle course. Despite this evidence base, the pivotal trials that led to approval, NETTER-1 for Lutathera (FDA, January 2018) and VISION for Pluvicto (FDA, March 2022), used fixed activities and a fixed number of cycles, and the resulting labels do not require patient-specific dosimetry for in-label use.\n\nThe current step is guideline consolidation: the joint EANM/SNMMI procedure guideline for 177Lu-PSMA radioligand therapy (2023) states plainly that fixed dosing was how the drug was approved and that dosimetry is not mandatory in-label, while EANM's 2022 dosimetry-committee recommendations and its 2024 guidance for first-in-human studies push in the opposite direction, calling for patient-specific absorbed-dose calculation as standard practice, especially early in a new drug's development. The emerging and speculative steps are quantitative SPECT/CT and total-body PET made fast and automated enough for routine clinical dosimetry, and trials that prospectively randomise dosimetry-guided dosing against the fixed-activity standard of care.","asOf":"2026-09-22","links":[{"label":"From the MIRD Committee: history and founding, 1965 (J Nucl Med)","url":"https://jnm.snmjournals.org/content/jnumed/50/2/25N.full.pdf"},{"label":"Sundlöv et al., individualised 177Lu-DOTATATE treatment based on kidney dosimetry (Eur J Nucl Med Mol Imaging 2017)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5506097/"},{"label":"Joint EANM/SNMMI procedure guideline for 177Lu-PSMA-RLT (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"}],"tags":[],"related":["lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","spect-ct","total-body-pet-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry","gray-unit"],"trials":["netter-1","vision"],"people":["clemens-kratochwil","ken-herrmann"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1965-1968","title":"The MIRD schema","description":"The Society of Nuclear Medicine forms the Medical Internal Radiation Dose (MIRD) Committee in 1965. Its 1968 MIRD Pamphlet No. 1 (Loevinger and Berman) introduces the absorbed-fraction and S-value formalism for internal dosimetry, replacing older exposure-based (roentgen) methods and forming the basis of modern dosimetry software.","refs":["dosimetry"],"status":"historic"},{"era":"2012-2017","title":"Prospective personalised PRRT dosimetry trials","description":"Swedish groups develop and prospectively test image-based, patient-specific PRRT dosing: Sandström and Garske-Román's Uppsala cohort of 200 patients caps 177Lu-DOTATATE at a 23 Gy renal dose rather than a fixed cycle count, and Sundlöv's Lund phase 2 trial (NCT01456078) individualises cycles up to a 27 Gy renal biologically effective dose, reporting the approach as feasible and safe.","refs":["prrt","sstr2","idea-net-dosimetry-prrt"],"status":"historic"},{"era":"2018-2022","title":"Fixed-activity dosing wins regulatory approval","description":"Despite the personalised-dosimetry evidence base, the pivotal trials that gained approval both use fixed dosing: NETTER-1 (Lutathera, FDA January 2018) gives 7.4 GBq every 8 weeks for 4 doses, and VISION (Pluvicto, FDA March 2022) gives 7.4 GBq every 6 weeks for up to 6 doses, with dosimetry collected in a VISION sub-study of only 29 patients rather than used to set the dose.","refs":["netter-1","vision","lutathera","pluvicto"],"status":"historic"},{"era":"2022-2024","title":"Guidelines diverge on whether dosimetry should be mandatory","description":"EANM's dosimetry committee publishes recommendations for 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands (2022). The joint EANM/SNMMI procedure guideline for 177Lu-PSMA radioligand therapy (2023) states that '[177Lu]Lu-PSMA-617 was approved using fixed standard treatment activities, and patient individual dosimetry is not mandatory for in-label use', while acknowledging significant inter-patient variability. EANM's 2024 guidance document for first-in-human studies and early-phase trials calls for patient-specific absorbed-dose calculation as standard in that earlier setting.","refs":["radioligand-dosimetry","in-vivo-dosimetry"],"status":"current"},{"era":"2024-2028","title":"Emerging: faster quantitative imaging for routine dosimetry","description":"Work continues on shortening and simplifying SPECT/CT-based kidney and bone-marrow dosimetry protocols (for example, reducing the number of post-therapy imaging time points needed) and on total-body PET platforms whose sensitivity could make same-day, whole-body quantitative dosimetry practical outside specialist academic centres.","refs":["spect-ct","total-body-pet-screening","idea-total-body-pet-dosimetry"],"status":"emerging"},{"era":"2028+","title":"Speculative: dosimetry-personalised dosing as standard of care","description":"If ongoing and future randomised trials show that dosimetry-guided cycle number or activity improves outcomes or reduces toxicity compared with fixed dosing, regulators could require or incentivise individualised dosing for new and existing radioligand therapies rather than leaving it as an optional academic practice.","refs":["idea-net-dosimetry-prrt"],"status":"speculative"}],"watch":[{"item":"Joint EANM/SNMMI procedure guideline for 177Lu-PSMA-RLT, next revision","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/","refs":["radioligand-dosimetry"]}],"route":"/roadmaps/dosimetry-roadmap/"}
{"id":"sstr-theranostics-roadmap","kind":"roadmap","name":"SSTR theranostics roadmap: octreotide scintigraphy → 68Ga-DOTATATE → 177Lu-DOTATATE → alpha","aka":[],"tldr":"Neuroendocrine tumours were the proving ground for the whole idea of theranostics: find a receptor on the tumour, image it with a low-dose radioactive scan, then treat with a matched higher-dose version of the same molecule. That sequence took thirty years to build and is now being extended with more powerful alpha-particle versions.","summary":"The somatostatin-receptor pathway is where theranostics as a field began. Indium-111 pentetreotide (OctreoScan), approved by the FDA on 2 June 1994, was the first peptide-based radiopharmaceutical approved for any indication, imaging somatostatin receptor 2 (SSTR2) on neuroendocrine tumours by gamma-camera scintigraphy. Gallium-68 dotatate (Netspot), approved 1 June 2016, replaced planar scintigraphy with quantitative PET, giving markedly better sensitivity for localising these often small, slow-growing tumours.\n\nThe therapeutic half of the pair, lutetium-177 dotatate (Lutathera), was approved by the FDA on 26 January 2018 on the strength of the NETTER-1 trial, becoming the first FDA-approved peptide receptor radionuclide therapy (PRRT) and confirming that the diagnostic-therapeutic pairing translates into a survival and progression-free-survival benefit, not just better pictures. The label was extended to first-line use in higher-grade (grade 2/3) tumours in 2024 on the strength of the NETTER-2 trial (72% reduction in risk of progression or death versus high-dose octreotide), and to adolescent patients (12 years and older) in April 2024, the first FDA-approved radiopharmaceutical for that age group.\n\nThe current frontier is alpha-emitting versions of the same pharmacophore for patients whose disease progresses after beta-emitting PRRT: 225Ac-DOTATATE (RYZ101) is in the phase 3 ACTION-1 trial, and 212Pb-DOTAMTATE (AlphaMedix) reported in October 2025 that its phase 2 ALPHAMEDIX-02 trial met all primary efficacy endpoints in both PRRT-naive and PRRT-exposed patients. A further extension under investigation is SSTR2-expressing meningioma, a non-oncological-in-the-classical-sense but SSTR2-driven tumour, where 68Ga-DOTATATE PET has been used since 2015 to delineate disease and 225Ac-DOTATATE (RYZ101) is now in an early-phase trial for progressive or recurrent intracranial meningioma.","asOf":"2026-09-22","links":[{"label":"FDA: Netspot (gallium Ga 68 dotatate) approval, June 2016","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208547Orig1s000Approv.pdf"},{"label":"FDA: Lutathera (lutetium Lu 177 dotatate) approval for GEP-NETs, January 2018","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-treatment-gep-nets"},{"label":"Novartis: NETTER-2 phase 3 results, first-line PRRT, January 2024","url":"https://www.novartis.com/us-en/news/media-releases/novartis-lutathera-significantly-reduced-risk-disease-progression-or-death-72-first-line-treatment-patients-advanced-gastroenteropancreatic-neuroendocrine-tumors"},{"label":"Sanofi: AlphaMedix (212Pb-DOTAMTATE) ALPHAMEDIX-02 phase 2 results, October 2025","url":"https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053"}],"tags":[],"related":["ga-68","in-111","lu-177","ac-225","pb-212"],"indications":["neuroendocrine","pancreatic-net","small-intestinal-net","meningioma"],"sections":[],"technologies":["sstr-pet","prrt","targeted-alpha-therapy"],"targets":["sstr2"],"drugs":["lutathera","ga68-dotatate","ryz101","alphamedix","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1","action-1","alphamedix-02"],"people":[],"bottlenecks":[],"keyPapers":["paper-netter-1-nejm-2017","paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1994","title":"OctreoScan: the first peptide radiopharmaceutical","description":"The FDA approves indium-111 pentetreotide (OctreoScan, Mallinckrodt/Curium) on 2 June 1994 for scintigraphic localisation of neuroendocrine tumours bearing somatostatin receptors, the first radiolabelled peptide ever approved and the foundation of the theranostic principle in nuclear medicine.","refs":["neuroendocrine"],"status":"historic"},{"era":"2016","title":"68Ga-DOTATATE: PET replaces scintigraphy","description":"The FDA approves Netspot (a kit for gallium-68 dotatate injection, Advanced Accelerator Applications) on 1 June 2016 as the first gallium-68 PET agent, giving markedly better sensitivity than OctreoScan for localising somatostatin-receptor-positive neuroendocrine tumours.","refs":["ga68-dotatate","sstr-pet"],"status":"historic"},{"era":"2018","title":"Lutathera: the first approved PRRT","description":"The FDA approves lutetium Lu 177 dotatate (Lutathera) on 26 January 2018 for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, based on the NETTER-1 trial (79% reduction in risk of progression or death versus high-dose octreotide LAR), the first FDA-approved peptide receptor radionuclide therapy.","refs":["lutathera","netter-1","paper-netter-1-nejm-2017"],"status":"historic"},{"era":"2024","title":"NETTER-2 moves PRRT to first line","description":"The FDA expands the Lutathera label in 2024 to first-line use in newly diagnosed grade 2/3 advanced GEP-NETs, based on the NETTER-2 trial (72% reduction in risk of progression or death versus high-dose octreotide LAR alone), and separately approves Lutathera for pediatric patients 12 years and older in April 2024, the first FDA-approved radiopharmaceutical for that age group.","refs":["paper-netter-2-lancet-2024","lutathera"],"status":"historic"},{"era":"2022-2026","title":"Alpha-emitting SSTR radioligands after beta PRRT","description":"225Ac-DOTATATE (RYZ101) enters the phase 3 ACTION-1 trial for GEP-NETs progressing after 177Lu-DOTATATE/TOC. 212Pb-DOTAMTATE (AlphaMedix) receives FDA Breakthrough Therapy designation in 2024 and reports in October 2025 that its phase 2 ALPHAMEDIX-02 trial met all primary efficacy endpoints, with a 60% objective response rate in PRRT-naive patients.","refs":["action-1","alphamedix-02","ryz101","alphamedix"],"status":"current"},{"era":"2025-2028","title":"Emerging: SSTR2 theranostics in meningioma","description":"68Ga-DOTATATE PET, used since 2015 to delineate SSTR2-positive meningioma tissue from tumour-free tissue, is now the imaging companion for a therapeutic extension: 225Ac-DOTATATE (RYZ101) enters a trial for progressive or recurrent intracranial meningioma (grades 1-3) at Ohio State, testing whether the SSTR theranostic pairing extends beyond classic neuroendocrine tumours.","refs":["meningioma","sstr2"],"status":"emerging"},{"era":"2028+","title":"Speculative: antagonist ligands and earlier lines","description":"SSTR antagonist radioligands, which bind more receptor sites than the agonists (octreotide, DOTATATE) used to date, are proposed to increase tumour dose further. If alpha-emitting SSTR therapies read out positively, the sequence could extend to first-line use ahead of somatostatin analogues, and to indications such as SSTR-expressing breast cancer now in early trials.","refs":["idea-net-antagonist-ligands"],"status":"speculative"}],"watch":[{"item":"ACTION-1 (RYZ101) phase 3 primary completion","expected":"Primary Completion (Estimated): 2026-12","source":"https://clinicaltrials.gov/study/NCT05477576","refs":["action-1"]},{"item":"RYZ101 for progressive/recurrent intracranial meningioma, Ohio State trial","source":"https://clinicaltrials.gov/study/NCT07150806","refs":["meningioma"]}],"route":"/roadmaps/sstr-theranostics-roadmap/"}
{"id":"psma-theranostics-roadmap","kind":"roadmap","name":"PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha","aka":[],"tldr":"Prostate-specific membrane antigen was found on prostate cancer cells in 1987. It took until 2020-2022 for scans and treatments that target it to reach approval, but once they did, PSMA PET and Pluvicto changed how metastatic prostate cancer is staged and treated, and the same target is now being tried earlier in the disease and with more powerful alpha particles.","summary":"Prostate-specific membrane antigen (PSMA) was first identified in 1987 when Horoszewicz and Murphy raised the monoclonal antibody 7E11-C5 against the LNCaP prostate cancer cell line; Heston and Fair's group at Memorial Sloan Kettering cloned the PSMA gene in 1993. The first PSMA-targeted imaging agent to reach approval, indium-111 capromab pendetide (ProstaScint), was approved by the FDA on 28 October 1996, but bound only an intracellular epitope and had limited clinical impact.\n\nThe modern era begins with small-molecule PSMA ligands: Eder and colleagues at the German Cancer Research Center (DKFZ) Heidelberg synthesised the gallium-68-labelled HBED-CC compound that became PSMA-11 in 2012, building on first-in-human work from 2011. It took until 1 December 2020 for the FDA to approve 68Ga-PSMA-11 (jointly, as separate applications from UCSF and UCLA), the first PSMA PET agent approved in the US, followed by the first commercially distributable PSMA PET agent, Pylarify (piflufolastat F 18), on 26 May 2021. On the therapy side, Kratochwil's Heidelberg group had already shown in 2016 that the corresponding alpha-emitting ligand, 225Ac-PSMA-617, could produce complete responses; the beta-emitting version, 177Lu-PSMA-617 (Pluvicto), was approved by the FDA on 23 March 2022 for post-chemotherapy mCRPC, based on the VISION trial (a 38% reduction in risk of death).\n\nThe label then moved earlier: on 28 March 2025 the FDA expanded Pluvicto's indication, based on the PSMAfore trial, to PSMA-positive mCRPC patients who have progressed on one androgen receptor pathway inhibitor and are considered appropriate to delay chemotherapy, removing the prior-taxane requirement and roughly tripling the eligible US population. The alpha-emitting analogue of Pluvicto, 225Ac-PSMA-617 (AAA817, Novartis), and a second alpha PSMA ligand, FPI-2265 (225Ac-PSMA-I&T, Fusion Pharmaceuticals), are both now in phase 3 programmes for patients whose disease has progressed on 177Lu-PSMA, the next planned step in the sequence.","asOf":"2026-09-22","links":[{"label":"FDA: Ga 68 PSMA-11 injection approval (UCSF/UCLA), December 2020","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212643Orig1s000Approv.pdf"},{"label":"Lantheus: FDA approval of Pylarify, May 2021","url":"https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-us-fda-approval-pylarifyr-piflufolastat-f-18"},{"label":"FDA: Pluvicto (lutetium Lu 177 vipivotide tetraxetan) approval summary, March 2022 (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10159870/"},{"label":"FDA: Pluvicto label expansion based on PSMAfore, March 2025","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication"}],"tags":[],"related":["f-18","ga-68","in-111","lu-177","ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["psma-pet","lu177-radioligand-therapy","targeted-alpha-therapy"],"targets":["psma"],"drugs":["ga68-psma-11","pylarify","pluvicto","illuccix","locametz","lu177-psma-it","ac225-psma"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","alphabreak"],"people":["clemens-kratochwil","uwe-haberkorn","michael-morris","thomas-hope","hofman-michael"],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021","paper-propsma-hofman-lancet-2020"],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1987-1996","title":"PSMA discovered; first imaging agent approved","description":"Horoszewicz, Kawinski and Murphy raise the 7E11-C5 monoclonal antibody against PSMA in 1987; Heston and Fair's group at Memorial Sloan Kettering clone the PSMA gene in 1993. The FDA approves the first PSMA-targeted imaging agent, indium-111 capromab pendetide (ProstaScint, Cytogen), on 28 October 1996, though the antibody binds an intracellular epitope and offers limited sensitivity.","refs":["prostate"],"status":"historic"},{"era":"2011-2012","title":"Small-molecule PSMA ligands and first-in-human PET","description":"The Heidelberg group at the German Cancer Research Center (DKFZ) reports first-in-human imaging with a gallium-68-labelled small-molecule PSMA inhibitor in 2011; Eder and colleagues publish the synthesis of the HBED-CC-chelated compound that becomes PSMA-11 in 2012, replacing antibody-based imaging with fast, high-contrast small-molecule PET.","refs":["psma-pet","uwe-haberkorn"],"status":"historic"},{"era":"2016","title":"225Ac-PSMA-617: alpha therapy proof of concept","description":"Kratochwil, Bruchertseifer and colleagues report complete biochemical and imaging responses with 225Ac-PSMA-617 in two heavily pretreated patients with mCRPC (J Nucl Med, 2016), the first demonstration that a PSMA-targeted alpha emitter could produce deep responses where beta therapy and other options had failed.","refs":["clemens-kratochwil","ac225-psma"],"status":"historic"},{"era":"2020-2022","title":"PSMA PET and Pluvicto reach approval","description":"The FDA approves 68Ga-PSMA-11 on 1 December 2020 (UCSF and UCLA applications), the first PSMA PET agent approved in the US; Pylarify (piflufolastat F 18, Lantheus) follows on 26 May 2021 as the first commercially distributed PSMA PET agent. Pluvicto (177Lu-PSMA-617, Novartis) is approved 23 March 2022 for PSMA-positive mCRPC after androgen receptor pathway inhibition and taxane chemotherapy, based on VISION (38% reduction in risk of death), the first FDA-approved targeted radioligand therapy for prostate cancer.","refs":["ga68-psma-11","pylarify","pluvicto","vision","paper-vision-nejm-2021"],"status":"historic"},{"era":"2025","title":"Pluvicto moves to an earlier line","description":"The FDA expands the Pluvicto label on 28 March 2025, based on the PSMAfore trial, to adults with PSMA-positive mCRPC who have progressed on at least one androgen receptor pathway inhibitor and are considered appropriate to delay taxane chemotherapy, removing the prior-taxane requirement and roughly tripling the eligible US patient population.","refs":["psmafore","pluvicto"],"status":"current"},{"era":"2024-2028","title":"Alpha-emitting PSMA ligands after 177Lu-PSMA","description":"Two alpha-emitting PSMA ligands are in phase 2/3 development for patients progressing after 177Lu-PSMA therapy: FPI-2265 (225Ac-PSMA-I&T, Fusion Pharmaceuticals/AstraZeneca) in AlphaBreak, and AAA817 (225Ac-PSMA-617, Novartis) in a phase 3 programme including PSMAcTION (NCT06780670) and a combination trial with an androgen receptor pathway inhibitor (NCT06855277).","refs":["alphabreak","ac225-psma"],"status":"emerging"},{"era":"2028+","title":"Speculative: PSMA-directed therapy at diagnosis","description":"Ideas under discussion include PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent disease, alpha-emitting PSMA therapy at first metastatic diagnosis rather than after multiple prior lines, and using PSMA PET tumour volume as a formally qualified imaging biomarker for trials.","refs":["idea-psma-pet-guided-mdt","idea-alpha-first-mhspc","idea-tr2-psma-volume-qualification"],"status":"speculative"}],"watch":[{"item":"AAA817 + ARPI vs standard of care in PSMA-positive mCRPC, phase 3 primary completion","expected":"Primary Completion (Estimated): 2028-09-29","source":"https://clinicaltrials.gov/study/NCT06855277","refs":["novartis"]},{"item":"AAA817 vs standard of care after 177Lu-PSMA progression (PSMAcTION), primary completion","expected":"Primary completion date: Jun 27, 2028 (Anticipated)","source":"https://www.allclinicaltrials.com/study/NCT06780670","refs":["novartis"]},{"item":"AlphaBreak (FPI-2265) phase 2 primary completion","expected":"Estimated Completion: July 23, 2026","source":"https://www.ancora.ai/en/detailsradiopharm/NCT06402331","refs":["alphabreak","fusion-pharma"]}],"route":"/roadmaps/psma-theranostics-roadmap/"}
{"id":"neuro-imaging-roadmap","kind":"roadmap","name":"Neuro-oncology imaging roadmap: FDG PET → amino acid PET → SSTR2 theranostics in meningioma","aka":[],"tldr":"Ordinary sugar-based PET scans do not work well in the brain because healthy brain tissue itself uses a lot of sugar. Nuclear medicine had to develop tracers that light up brain tumours specifically, first amino acid tracers for gliomas and then a receptor tracer that also opens the door to a matched radioactive treatment for meningioma.","summary":"FDG PET has a structural limitation in the brain: normal grey matter has high baseline glucose uptake, so FDG contrast between tumour and healthy brain tissue is poor, unlike its performance in most body cancers. This drove development from the 1980s onward of radiolabelled amino acid tracers, principally 11C-methionine and later 18F-FET, which exploit the increased amino acid transport of tumour cells against a low physiological background in normal brain.\n\nThese tracers were gradually adopted into formal guidance: the PET-RANO working group and EANO published evidence-based recommendations for PET imaging in gliomas in 2016, followed by the joint EANM/EANO/RANO/SNMMI practice guideline (version 1.0) for glioma PET imaging with radiolabelled amino acids and FDG, published in 2019, standardising acquisition and interpretation (for example, a tumour-to-brain ratio threshold of 1.6-1.8 for 18F-FET). An updated RANO/EANO policy review in 2025 strengthened several of these recommendations, including for delineating tumour extent and distinguishing recurrence from treatment-related change.\n\nA parallel and largely separate strand targets meningioma, a tumour that (unlike most gliomas) reliably overexpresses somatostatin receptor 2 (SSTR2). Rachinger et al. (2015) showed that 68Ga-DOTATATE PET uptake correlates with SSTR2 expression and outperforms MRI sensitivity (90% vs 79%) for discriminating meningioma from tumour-free tissue, and it is now used for surgical and radiotherapy planning, particularly at the skull base. Because meningioma expresses the same target as neuroendocrine tumours, it has become a candidate for the same theranostic pairing: a phase 1/2 trial of the alpha emitter 225Ac-DOTATATE (RYZ101) in progressive or recurrent intracranial meningioma opened at Ohio State, testing whether the SSTR theranostic model developed for neuroendocrine tumours extends into neuro-oncology.","asOf":"2026-09-22","links":[{"label":"Rachinger et al., increased 68Ga-DOTATATE uptake discriminates meningioma and tumour-free tissue (J Nucl Med 2015)","url":"https://pubmed.ncbi.nlm.nih.gov/25635133/"},{"label":"Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for glioma PET, version 1.0 (2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6351513/"},{"label":"Update to the RANO working group and EANO recommendations for PET imaging in gliomas (Lancet Oncology 2025)","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00193-7/fulltext"},{"label":"ClinicalTrials.gov: RYZ101 for progressive/recurrent intracranial meningioma (NCT07150806)","url":"https://clinicaltrials.gov/study/NCT07150806"}],"tags":[],"related":["f-18","ga-68","c-11","ac-225"],"indications":["glioblastoma","meningioma"],"sections":[],"technologies":["pet","pet-ct","fdg-pet","sstr-pet","astatine-211-alpha-therapy"],"targets":["sstr2"],"drugs":["fludeoxyglucose-f18","ga68-dotatate","ryz101"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1980s-1990s","title":"FDG's limits in the brain drive amino acid PET","description":"FDG PET is limited in neuro-oncology by high physiological glucose uptake in normal grey matter, which reduces tumour-to-background contrast. This drives clinical development of radiolabelled amino acid tracers, principally 11C-methionine, which show much better contrast against normal brain from the 1980s onward.","refs":["fdg-pet","glioblastoma"],"status":"historic"},{"era":"2000s-2016","title":"18F-FET and the first evidence-based PET guidance for glioma","description":"O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET), an 18F-labelled amino acid tracer with a longer half-life than 11C-methionine, is adopted widely in Europe through the 2000s and 2010s. The PET-RANO working group and EANO publish the first evidence-based recommendations for the clinical use of PET imaging in gliomas in Neuro-Oncology in 2016.","refs":["glioblastoma"],"status":"historic"},{"era":"2015","title":"68Ga-DOTATATE PET for meningioma","description":"Rachinger et al. show, using spatially precise neuronavigated tissue sampling during surgery, that 68Ga-DOTATATE PET uptake correlates with SSTR2 expression and detects meningioma tissue with higher sensitivity than MRI (90% vs 79%), establishing SSTR2 PET as a tool for meningioma delineation, particularly in the skull base and after treatment.","refs":["meningioma","sstr2","ga68-dotatate"],"status":"historic"},{"era":"2019-2025","title":"Joint practice guidelines standardise glioma PET","description":"The joint EANM/EANO/RANO/SNMMI practice guideline (version 1.0) for imaging gliomas with PET using radiolabelled amino acids and FDG is published in 2019, standardising acquisition protocols and uptake thresholds (for example, an 18F-FET tumour-to-brain ratio of 1.6-1.8). An updated RANO/EANO policy review in 2025 strengthens the recommendation level for several uses, including delineating glioma extent and distinguishing recurrence from treatment-related change.","refs":["glioblastoma"],"status":"current"},{"era":"2020-2026","title":"68Ga-DOTATATE PET in routine meningioma management","description":"SSTR2 PET with 68Ga-DOTATATE or DOTATOC becomes an established adjunct to MRI for meningioma treatment planning, particularly for delineating disease extent at the skull base, detecting bony invasion, and distinguishing residual tumour from post-surgical or post-radiation change.","refs":["meningioma","sstr2"],"status":"current"},{"era":"2025-2028","title":"Emerging: SSTR2 theranostics extends into meningioma therapy","description":"A phase 1/2 trial of the alpha emitter 225Ac-DOTATATE (RYZ101) for progressive or recurrent intracranial meningioma (WHO grades 1-3) opens at Ohio State, using 68Ga-DOTATATE PET to select and follow patients, testing whether the diagnostic-therapeutic SSTR2 pairing developed for neuroendocrine tumours can extend into a tumour type managed mainly by surgery and radiotherapy.","refs":["meningioma"],"status":"emerging"},{"era":"2028+","title":"Speculative: broader receptor and alpha-emitter use in brain tumours","description":"If SSTR2 theranostics in meningioma shows benefit, other brain and skull-base tumours with a defined receptor target could follow the same diagnostic-therapeutic pairing, and locoregional alpha-emitter delivery (for example convection-enhanced delivery of astatine-211 conjugates, under early investigation for glioma) could extend targeted radiotherapy to tumours where systemic dosing is limited by the blood-brain barrier.","refs":["astatine-211-alpha-therapy"],"status":"speculative"}],"watch":[{"item":"RYZ101 for progressive/recurrent intracranial meningioma, Ohio State trial","source":"https://clinicaltrials.gov/study/NCT07150806","refs":["meningioma"]}],"route":"/roadmaps/neuro-imaging-roadmap/"}
{"id":"caix","kind":"target","name":"CAIX (carbonic anhydrase IX)","aka":["CA9","G250 antigen","MN antigen"],"tldr":"A protein that clear cell kidney cancer makes almost all the time because of a gene fault. It helps the tumour survive in low-oxygen conditions, and antibodies that stick to it can be used to find or treat the cancer.","summary":"Carbonic anhydrase IX is a transmembrane enzyme with an extracellular catalytic domain that helps regulate intracellular and extracellular pH, allowing tumour cells to survive an acidic, hypoxic microenvironment. Its expression is switched on by the HIF-1 transcription factor: in clear cell renal cell carcinoma (ccRCC), loss-of-function mutation or deletion of the VHL tumour-suppressor gene (found in roughly 75-95% of ccRCC cases) leaves HIF-1α constitutively active even without hypoxia, so CAIX is expressed diffusely and strongly on almost all ccRCC cells, in contrast to normal kidney, which does not express it.\n\nThis expression pattern (near-ubiquitous in ccRCC, essentially absent in normal renal parenchyma and in non-clear-cell kidney tumours) is what makes CAIX attractive: it is a differential diagnostic marker for ccRCC as well as a therapeutic target. The chimeric monoclonal antibody girentuximab (cG250) binds a conformational epitope on the catalytic domain, internalises via clathrin-coated vesicles and recycles rather than being degraded, giving long intracellular retention. Because girentuximab is a full antibody, tumour-to-background contrast builds slowly and imaging is typically read several days after injection.\n\nAs a target, CAIX's strength is its consistency and specificity in ccRCC; its weakness for antibody-based approaches is slow pharmacokinetics (days, not hours) and the fact that HIF-2α-driven, VHL-independent disease later in progression can show falling CAIX expression, which has been linked to worse prognosis. Small-molecule and peptide CAIX ligands (for example 68Ga-DPI-4452) have since been developed to give same-day imaging with high tumour-to-background contrast.","asOf":"2026-09-22","links":[{"label":"PMC review: CAIX in renal cell carcinoma, implications for imaging and therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7582814/"},{"label":"PMC: application of CAIX-targeted radiotracers in ccRCC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12976585/"},{"label":"Spandidos: monoclonal antibody G250 targeting CAIX, internalisation and epitope","url":"https://www.spandidos-publications.com/10.3892/ijo.2014.2658/download"},{"label":"JNM editorial: kick-starting molecular theranostics in renal cell carcinoma (VHL/HIF, girentuximab, 68Ga-DPI-4452)","url":"https://jnm.snmjournals.org/content/65/5/744"}],"tags":["renal cell carcinoma","hypoxia","antibody target"],"related":["girentuximab-zr89","caix-pet","rcc","hif-vhl","idea-caix-theranostics","nct06750419","nct07197580","telix","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CA9","biology":"A transmembrane carbonic anhydrase whose extracellular catalytic domain hydrates CO2 to bicarbonate and protons, helping tumour cells regulate pH and survive hypoxia. Its expression is switched on by the HIF-1 pathway, so it is expressed at very high, uniform density in VHL-mutant clear cell renal cell carcinoma while normal kidney does not express it.","whereFound":["Clear cell renal cell carcinoma: overexpressed in >90-95% of cases, driven by VHL/HIF-1 pathway loss","Normal kidney parenchyma: essentially absent","Some hypoxic non-renal tumours (expression follows tumour hypoxia rather than a fixed tissue pattern)","Normal gastrointestinal tract: low-level physiological expression"],"targetClass":"enzyme","prevalence":[],"route":"/targets/caix/"}
{"id":"nis-symporter","kind":"target","name":"NIS (sodium-iodide symporter)","aka":["Sodium/iodide cotransporter","SLC5A5"],"tldr":"A protein in the thyroid that pulls iodine out of the blood to make thyroid hormone. It is the reason radioactive iodine can find and treat thyroid cancer almost anywhere in the body.","summary":"NIS is a 13-transmembrane-domain glycoprotein on the basolateral membrane of thyroid follicular cells that actively co-transports two sodium ions with one iodide ion, using the electrochemical sodium gradient generated by Na+/K+-ATPase, as the first step of thyroid hormone synthesis. Its expression in the thyroid is driven by thyroid-stimulating hormone (TSH) acting through the cAMP pathway, which is why thyroid-stimulating hormone withdrawal or recombinant human TSH (thyrotropin alfa) is used clinically to maximise iodide uptake before radioiodine scanning or therapy.\n\nMore than 70% of differentiated (papillary and follicular) thyroid cancers retain enough NIS expression to concentrate iodide, which is the biological basis of whole-body radioiodine scanning and I-131 therapy for remnant ablation and metastatic disease. NIS is also expressed, at lower levels, in several extrathyroidal tissues: salivary glands, gastric mucosa, lactating breast, lacrimal glands, choroid plexus and placenta. Uptake in salivary glands and stomach is well below thyroid levels and the absorbed dose in these tissues is small relative to the thyroid, but it is still the mechanism behind the sialadenitis (dry mouth, taste change) and, less often, gastritis seen after high-activity I-131 therapy.\n\nAs a target, NIS is close to ideal for differentiated thyroid cancer: high density, non-internalising simple ion transport, and near-total tissue restriction outside a few low-uptake sites. Its main practical limitation is that a minority of thyroid cancers dedifferentiate and lose NIS expression (radioiodine-refractory disease), and normal-tissue uptake in salivary gland and stomach still causes most of the non-thyroid toxicity of I-131 therapy.","asOf":"2026-09-22","links":[{"label":"PMC: modulation of NIS expression in salivary gland tissue and I-131 uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3752512/"},{"label":"PMC: the sodium iodide symporter (NIS) - regulation and approaches to therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3408573/"},{"label":"PMC: sodium/iodide symporter - molecular physiology and preclinical applications (tissue distribution table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5739519/"},{"label":"MedlinePlus Genetics: SLC5A5 gene","url":"https://medlineplus.gov/genetics/gene/slc5a5/"}],"tags":["thyroid","ion transporter","theranostics"],"related":["radioactive-iodine","radioiodine-therapy","thyroid","thyrotropin-alfa","radioiodine-term","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC5A5","biology":"A basolateral membrane glycoprotein that actively co-transports two sodium ions with one iodide ion into thyroid follicular cells, the first step of thyroid hormone synthesis, driven by TSH via the cAMP pathway. Because most differentiated thyroid cancer retains this transporter, it is the biological basis for diagnostic and therapeutic use of radioactive iodine.","whereFound":["Thyroid follicular cells: high, TSH-driven expression; basis of normal thyroid hormone synthesis","Differentiated thyroid cancer: retained in >70% of papillary and follicular carcinomas","Salivary gland striated ducts: moderate expression, clinically relevant because of I-131 sialadenitis","Gastric mucosa (basolateral): moderate expression, secretes iodide into gastric juice","Lactating mammary gland, lacrimal gland, choroid plexus, placenta: lower-level physiological expression"],"targetClass":"other","prevalence":[],"route":"/targets/nis-symporter/"}
{"id":"norepinephrine-transporter","kind":"target","name":"Norepinephrine transporter (NET)","aka":["NET","Noradrenaline transporter"],"tldr":"A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.","summary":"The norepinephrine transporter is a 12-transmembrane-domain protein of presynaptic sympathetic neurons and adrenal medullary chromaffin cells that terminates noradrenergic signalling by taking norepinephrine back into the cell (uptake-1), an active, sodium- and chloride-dependent, ATP-driven process roughly 50-fold more efficient than passive diffusion. Once inside, norepinephrine (and NET's synthetic analogue metaiodobenzylguanidine, MIBG) can be stored in secretory vesicles via the vesicular monoamine transporters (VMAT1/2) or remain in the cytoplasm.\n\nTumours that arise from sympathetic neural crest precursors - neuroblastoma, phaeochromocytoma and paraganglioma - retain NET expression at high frequency (around 90% of neuroblastomas are NET-positive), and expression correlates with MIBG avidity on imaging. Radioiodinated MIBG (123I for diagnosis, 131I for therapy) is taken up through NET, giving both a diagnostic scan and, at therapeutic activities, a targeted radiotherapy. Other transporters (OCT1-3, MATE1/2-K) contribute to non-specific uptake into liver, salivary gland and heart and to renal clearance, and drugs that block NET (tricyclic antidepressants, some stimulants) must be stopped before MIBG scanning or therapy because they blunt tumour uptake.\n\nAs a target, NET's strength is high, tumour-restricted expression in an otherwise hard-to-image tumour family, plus intracellular retention via VMAT once inside the cell. Its main limitations are heterogeneous expression (MYCN-amplified, poorly differentiated neuroblastomas tend to have lower NET expression and are less MIBG-avid) and competition from other transporters that reduce specificity and complicate dosimetry.","asOf":"2026-09-22","links":[{"label":"DMD: clinical applications and roles of transporters in disposition, tumour targeting and tissue toxicity of MIBG","url":"https://dmd.aspetjournals.org/content/50/9/1218"},{"label":"JNM (SNMMI supplement): norepinephrine transporter as a target for imaging and therapy","url":"https://jnm.snmjournals.org/content/58/Supplement_2/39S"},{"label":"PMC: 'Nothing but NET' - NET expression and efficacy of 131I-MIBG therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4237663/"}],"tags":["neuroendocrine","paediatric","transporter"],"related":["i131-mibg","iobenguane-i-131","mibg-theranostics","pheochromocytoma-paraganglioma","neuroblastoma","neuroblastoma-high-risk","metastatic-ppgl","hereditary-ppgl","idea-mfbg-pet-replaces-mibg","nct04724369","paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","i-123","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC6A2","biology":"A presynaptic membrane transporter that takes norepinephrine back into sympathetic neurons and adrenal chromaffin cells after release, an active sodium- and chloride-dependent process. Tumours arising from sympathetic neural crest precursors (neuroblastoma, phaeochromocytoma, paraganglioma) retain this transporter at high frequency, allowing the norepinephrine analogue MIBG to be carried into tumour cells for imaging and therapy.","whereFound":["Neuroblastoma: NET-positive in roughly 90% of tumours; MYCN-amplified tumours tend to have lower expression","Phaeochromocytoma and paraganglioma: NET expressed in chromaffin-derived tumour cells, uptake reinforced by VMAT storage","Normal sympathetic nerve terminals and adrenal medulla: physiological expression"],"targetClass":"other","prevalence":[],"route":"/targets/norepinephrine-transporter/"}
{"id":"amyloid-beta","kind":"target","name":"Amyloid beta plaques","aka":["Aβ","beta-amyloid neuritic plaques"],"tldr":"Sticky clumps of protein that build up in the brain in Alzheimer's disease. PET scans using tracers that bind these clumps can show a doctor how much amyloid is present, well before it would show up on a brain biopsy.","summary":"Amyloid beta is a peptide, cleaved from the amyloid precursor protein, that misfolds and aggregates into extracellular neuritic plaques, one of the two neuropathological hallmarks of Alzheimer's disease (the other being tau neurofibrillary tangles). PET tracers such as 18F-florbetapir bind fibrillar amyloid aggregates with nanomolar affinity (Kd approximately 3.7 nM for florbetapir) and do not appreciably bind tau, so they read out plaque burden rather than tangle burden.\n\nFlorbetapir (Amyvid) was FDA-approved in 2012 for PET imaging to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease; its label was updated in June 2025 to add selection of patients for amyloid-targeting therapy, reflecting the arrival of anti-amyloid antibody drugs whose eligibility and monitoring depend on amyloid PET or blood biomarkers. Other approved 18F amyloid tracers include florbetaben (Neuraceq) and flutemetamol (Vizamyl); all three are stilbene or benzothiazole derivatives related to the original 11C-Pittsburgh compound B.\n\nAs an imaging target, amyloid's strength is that a negative scan has high negative predictive value (sparse or no plaque makes an Alzheimer's diagnosis unlikely), which is clinically decisive. Its main limitation is specificity for a diagnosis: a positive scan indicates plaque is present but this can also occur in cognitively normal older adults and in other neurodegenerative conditions, so a positive result does not by itself confirm Alzheimer's disease, and none of the approved tracers is validated to monitor treatment response or to predict conversion to dementia.","asOf":"2026-09-22","links":[{"label":"FDA label: Amyvid (florbetapir F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf"},{"label":"Eli Lilly: FDA approves updated Amyvid label for amyloid-targeting therapy selection (25 June 2025)","url":"https://investor.lilly.com/news-releases/news-release-details/fda-approves-updated-label-lillys-amyvid-florbetapir-f-18"},{"label":"PMC: the role of amyloid PET in imaging neurodegenerative disorders","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9165727/"},{"label":"CMS national coverage determination memo: beta-amyloid PET in dementia","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=265"}],"tags":["neurology","Alzheimer's disease","protein aggregate"],"related":["tau-protein","f-18","c-11"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A peptide cleaved from the amyloid precursor protein that misfolds and aggregates into extracellular neuritic plaques, one of the two defining pathologies of Alzheimer's disease. PET tracers bind fibrillar amyloid aggregates with high affinity, giving an in-vivo readout of plaque burden that was previously only obtainable at autopsy.","whereFound":["Alzheimer's disease: neuritic plaques throughout association cortex; presence and density scored on amyloid PET","Cognitively normal older adults: a minority show plaque on amyloid PET without dementia","Cerebral amyloid angiopathy and some other neurodegenerative conditions: variable vascular and parenchymal amyloid"],"targetClass":"other","prevalence":[],"route":"/targets/amyloid-beta/"}
{"id":"tau-protein","kind":"target","name":"Tau protein (neurofibrillary tangles)","aka":["PHF-tau","aggregated tau","NFTs"],"tldr":"A protein that normally helps hold nerve cells together but, in Alzheimer's disease, twists into tangles inside the cells. A PET tracer called flortaucipir binds these tangles so doctors can see how far the disease has spread in the brain.","summary":"Tau is a microtubule-associated protein that, in Alzheimer's disease, becomes abnormally hyperphosphorylated and aggregates intracellularly into paired helical filaments that form neurofibrillary tangles (NFTs) - one of the two pathologies (with amyloid beta plaques) required for a neuropathological diagnosis of Alzheimer's disease. Tangles accumulate and spread through the brain in a stereotyped anatomical sequence (Braak staging), which is why tau PET, unlike amyloid PET, can track disease stage and distribution rather than simple positive/negative status.\n\nFlortaucipir F18 (Tauvid) binds aggregated PHF-tau with a dissociation constant of 0.57 nM in vitro and shows negligible binding to beta-amyloid, so it reports tangle pathology specifically. It was FDA-approved in May 2020, the first and to date only approved tau PET tracer, for estimating the density and distribution of NFTs in adults with cognitive impairment being evaluated for Alzheimer's disease; it is explicitly not indicated for chronic traumatic encephalopathy, because non-Alzheimer's tauopathies show different tau conformations that the tracer does not reliably detect. Some off-target binding to monoamine oxidase A/B occurs, seen in the choroid plexus, striatum and brainstem, and is excluded from image interpretation.\n\nAs a target, tau's strength is that its regional distribution tracks clinical stage and correlates better with cognitive decline than amyloid burden does. Its main limitation is that flortaucipir's sensitivity is lower in earlier-stage disease (the pivotal studies enrolled mostly terminally ill patients with advanced NFT pathology), and it cannot distinguish Alzheimer's tau from other tauopathies.","asOf":"2026-09-22","links":[{"label":"FDA label: Tauvid (flortaucipir F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212123s031lbl.pdf"},{"label":"FDA integrated review, NDA 212123 (mechanism of action, pivotal trial data)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212123Orig1s000IntegratedR.pdf"},{"label":"PMC: Tauvid, the first FDA-approved PET tracer for imaging tau pathology in Alzheimer's disease","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7911942/"},{"label":"Eli Lilly: FDA approval of Tauvid (28 May 2020)","url":"https://investor.lilly.com/node/43256/pdf"}],"tags":["neurology","Alzheimer's disease","protein aggregate"],"related":["amyloid-beta","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A microtubule-associated protein that becomes hyperphosphorylated and aggregates intracellularly into paired helical filaments forming neurofibrillary tangles, the second defining pathology of Alzheimer's disease. Tangles spread through the brain in a stereotyped anatomical sequence that correlates with clinical stage, distinguishing tau imaging from the simple positive/negative readout of amyloid imaging.","whereFound":["Alzheimer's disease: neurofibrillary tangles accumulate in a stereotyped pattern (Braak staging), correlating with cognitive impairment stage","Other tauopathies (progressive supranuclear palsy, Pick's disease, chronic traumatic encephalopathy): different tau conformations, not reliably detected by flortaucipir"],"targetClass":"other","prevalence":[],"route":"/targets/tau-protein/"}
{"id":"dopamine-transporter","kind":"target","name":"Dopamine transporter (DAT)","aka":["DAT"],"tldr":"A protein on the ends of brain cells that make dopamine, which recycles the dopamine after it has done its job. A scan using a tracer that sticks to this protein can show whether those brain cells are dying, which happens in Parkinson's disease.","summary":"The dopamine transporter sits on the axon terminals of presynaptic nigrostriatal dopaminergic neurons, which project from the substantia nigra to the striatum (caudate and putamen), and terminates dopaminergic signalling by taking dopamine back into the neuron after release. Because DAT density on the neuron surface tracks the number of intact nigrostriatal terminals, loss of DAT signal on imaging is a marker of neurodegeneration rather than a direct marker of disease-specific pathology.\n\nIoflupane I-123 (DaTscan/DATSCAN), a radioiodinated cocaine analogue, binds reversibly to DAT (Ki approximately 0.62 nM) and is imaged by SPECT 3-6 hours after injection, concentrating in the striatum in proportion to transporter density. It is FDA- and EMA-approved as an adjunct for striatal DAT visualisation in adults with suspected parkinsonian syndromes and suspected dementia with Lewy bodies, chiefly to help distinguish essential tremor (normal DAT scan) from Parkinsonian syndromes (reduced striatal DAT), and probable dementia with Lewy bodies from Alzheimer's disease.\n\nAs a target, DAT's strength is a clean anatomical readout (striatal uptake) that reliably separates presynaptic neurodegeneration from tremor of other causes. Its main limitation is lack of specificity between the parkinsonian syndromes themselves: DaTscan cannot distinguish idiopathic Parkinson's disease from multiple system atrophy or progressive supranuclear palsy, since all three cause nigrostriatal terminal loss. A range of common drugs (stimulants, some antidepressants, benztropine) bind DAT with high affinity and can interfere with image interpretation, so they typically need to be stopped before scanning.","asOf":"2026-09-22","links":[{"label":"FDA label: DATSCAN (ioflupane I 123 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022454s010lbl.pdf"},{"label":"FDA medical review, NDA 022454 (mechanism of action)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022454sOrig1s000MedR.pdf"},{"label":"PMC: clinical utility of dopamine transporter SPECT imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3812862/"}],"tags":["neurology","Parkinson's disease","transporter"],"related":["i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC6A3","biology":"A presynaptic membrane transporter on nigrostriatal dopaminergic neuron terminals that recycles dopamine after synaptic release. Its density in the striatum reflects the number of intact dopaminergic terminals, so loss of transporter signal is a marker of the neurodegeneration that occurs in Parkinsonian syndromes and dementia with Lewy bodies.","whereFound":["Substantia nigra pars compacta neuron terminals in the striatum: high physiological expression, lost with nigrostriatal degeneration","Parkinson's disease, multiple system atrophy, progressive supranuclear palsy: reduced striatal DAT signal (not distinguishable from each other by DAT imaging alone)","Essential tremor and dementia unrelated to Lewy body disease: normal DAT signal, used to rule out parkinsonian degeneration"],"targetClass":"other","prevalence":[],"route":"/targets/dopamine-transporter/"}
{"id":"bone-hydroxyapatite","kind":"target","name":"Bone mineral (hydroxyapatite)","aka":["Hydroxyapatite","bone mineral matrix"],"tldr":"The hard mineral that makes up bone. Certain radioactive drugs stick to this mineral wherever bone is being actively rebuilt, which is how bone scans find fractures, infection and cancer that has spread to bone, and how some treatments deliver radiation straight to bone metastases.","summary":"Bone is a composite of collagen protein and hydroxyapatite, a crystalline calcium phosphate mineral (Ca5(PO4)3OH). Bisphosphonates - and the older diphosphonates such as methylene diphosphonate (MDP) and hydroxymethylene diphosphonate (HDP/HMDP) - bind hydroxyapatite with high affinity through a P-C-P backbone that chelates surface calcium ions in a bidentate arrangement; when labelled with technetium-99m, the resulting Tc-99m-MDP or Tc-99m-HDP complex accumulates on bone in proportion to local blood flow and osteoblastic activity (new bone formation provides more, smaller hydroxyapatite crystals with greater surface area for binding), which is the basis of conventional bone scintigraphy.\n\nA related but chemically distinct mechanism is direct ionic exchange: 18F-fluoride ions substitute for hydroxyl groups in the hydroxyapatite lattice to form fluoroapatite, giving even faster, higher-contrast bone-turnover imaging on PET than Tc-99m bone scans. On the therapy side, the same hydroxyapatite affinity is exploited by bone-seeking radionuclide therapies: samarium-153 lexidronam (a Sm-153-EDTMP bisphosphonate complex) and radium-223 dichloride (a calcium mimetic incorporated directly into the mineral at sites of osteoblastic activity) both concentrate in areas of high bone turnover, including osteoblastic bone metastases, to deliver localised radiation for pain palliation or, for radium-223, a survival benefit in castration-resistant prostate cancer with bone metastases.\n\nAs a target, hydroxyapatite's strength is that bone-turnover tracers and therapies go wherever remodelling is happening, with no receptor saturation or internalisation step required (bone-seeking agents work by chemisorption or ionic exchange, not receptor binding). Its central weakness is a lack of disease specificity: fractures, arthritis, Paget's disease and infection all increase osteoblastic activity and light up alongside malignancy, so bone scans are sensitive but not specific, and specificity depends entirely on the clinical and radiological context.","asOf":"2026-09-22","links":[{"label":"StatPearls: bone scan (mechanism of Tc-99m MDP/HDP binding to hydroxyapatite)","url":"https://www.ncbi.nlm.nih.gov/books/NBK531486/"},{"label":"MDPI: bisphosphonates as radiopharmaceuticals - DOTAZOL review of bone-targeting chemistry","url":"https://www.mdpi.com/1422-0067/25/1/462"},{"label":"Applied Radiation and Isotopes review: targeted delivery to bone using bisphosphonate ligands","url":"https://ame.nd.edu/research-legacy/faculty-research-labs/rroeder/publications/publication-pdf/2016%20ADDR%20Cole.pdf"},{"label":"JNM: kinetics of bone-seeking radiotracers (Tc-99m-diphosphonate vs 18F-fluoride)","url":"https://jnm.snmjournals.org/content/jnumed/early/2013/03/11/jnumed.112.114298.full.pdf"}],"tags":["bone","mineral","palliation"],"related":["samarium-153-lexidronam","radium-223","phosphorus-32","spect","bone-metastases","f-18","tc-99m","ra-223","sm-153"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"The crystalline calcium phosphate mineral phase of bone, bound to a collagen matrix. Bisphosphonates and fluoride ions bind or exchange with this mineral at sites of active bone turnover through chemisorption or ionic substitution respectively, concentrating radiotracers or radionuclide therapy wherever bone remodelling, including reactive new bone at metastases, is occurring.","whereFound":["Sites of active bone remodelling generally: fractures, degenerative and inflammatory bone disease, Paget's disease, infection","Osteoblastic bone metastases (prostate, breast and other cancers): increased uptake reflecting reactive new bone formation","Normal growing skeleton: high uptake at epiphyseal growth plates and osteochondral junctions"],"targetClass":"other","prevalence":[],"route":"/targets/bone-hydroxyapatite/"}
{"id":"glut-hexokinase","kind":"target","name":"GLUT1 / hexokinase (glucose metabolism)","aka":["GLUT1","SLC2A1","hexokinase II","HK2"],"tldr":"The two-step system cells use to pull in and lock up glucose for energy. Many cancers rely on this system much more heavily than normal tissue, and a radioactive sugar look-alike called FDG exploits it to light up tumours on a PET scan.","summary":"Glucose enters cells through facilitative glucose transporters (GLUTs), of which GLUT1 is the most widely distributed, and is then immediately phosphorylated by hexokinase (chiefly hexokinase II, HK2, in tumours) to glucose-6-phosphate, trapping it inside the cell for glycolysis. Malignant cells characteristically upregulate both GLUT1 and HK2 to sustain the Warburg effect - a high rate of glycolysis even when oxygen is available, driven by oncogenic signalling (PI3K/AKT, MYC, RAS, loss of p53) and by hypoxia acting through HIF-1α, which transcriptionally activates GLUT1 and glycolytic enzymes.\n\n18F-fludeoxyglucose (FDG) is a glucose analogue that is carried into cells by GLUT1 (and GLUT3) exactly as glucose is, and phosphorylated by hexokinase to FDG-6-phosphate; because this metabolite lacks the 2'-hydroxyl group needed for further glycolytic processing and most tumours have low glucose-6-phosphatase activity to reverse the reaction, FDG-6-phosphate becomes metabolically trapped and accumulates in proportion to glycolytic flux. This is read out on PET as the standardised uptake value (SUV), the basis of FDG-PET staging, restaging and treatment response assessment across most solid tumours and lymphomas.\n\nAs a target, GLUT1/hexokinase's strength is near-universal upregulation across a very wide range of cancers, giving FDG-PET its broad utility as a single default oncology tracer. Its central weakness is specificity: any tissue with high glucose demand - brain, myocardium, active skeletal muscle, brown fat, healing wounds, infection and inflammation - also accumulates FDG strongly, so a positive scan requires anatomical and clinical correlation rather than being cancer-specific by itself; hyperglycaemia at the time of injection also competes with FDG uptake and reduces sensitivity.","asOf":"2026-09-22","links":[{"label":"PMC: roles of GLUT-1 and HK-II expression in tumour biology and FDG uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6508962/"},{"label":"PMC: mechanisms underlying FDG uptake in cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5120247/"},{"label":"StatPearls: fludeoxyglucose (18F) mechanism of action","url":"https://www.ncbi.nlm.nih.gov/books/NBK557653/"},{"label":"PMC: imaging cancer metabolism, underlying biology and pitfalls of FDG-PET","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6126440/"}],"tags":["metabolism","glycolysis","pan-cancer"],"related":["fludeoxyglucose-f18","fdg-pet","suv","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC2A1","biology":"Glucose enters cells through facilitative glucose transporters (chiefly GLUT1) and is then phosphorylated by hexokinase (chiefly hexokinase II in tumours), trapping it inside the cell. Cancer cells characteristically upregulate both proteins to sustain high glycolytic flux even in the presence of oxygen (the Warburg effect), which is what the glucose analogue FDG exploits for PET imaging.","whereFound":["Most solid tumours and lymphomas: GLUT1 and hexokinase II upregulated in proportion to glycolytic rate, the basis of FDG-PET","Brain (grey matter), myocardium, active skeletal muscle, brown adipose tissue: high physiological glucose uptake, a source of false-positive or confounding FDG signal","Sites of infection and inflammation: activated leukocytes also take up FDG avidly, another source of non-specific uptake"],"targetClass":"enzyme","prevalence":[],"route":"/targets/glut-hexokinase/"}
{"id":"integrin-avb3","kind":"target","name":"Integrin αvβ3","aka":["Integrin alpha-v beta-3","vitronectin receptor"],"tldr":"A docking protein on the surface of cells that are building new blood vessels, including the blood vessels a growing tumour needs. Peptides that mimic the docking sequence (RGD) can be radiolabelled to see where this new blood-vessel growth, or the tumour cells themselves, are most active.","summary":"Integrin αvβ3 is a heterodimeric transmembrane adhesion receptor that binds extracellular matrix proteins - vitronectin, fibronectin, fibrinogen - through their exposed arginine-glycine-aspartate (RGD) amino acid motif. It is minimally expressed on quiescent, resting blood vessel endothelium but becomes strongly upregulated on activated endothelial cells during angiogenesis, where it is required for the migration, survival and maturation of newly forming vessels, and it is also directly overexpressed on the tumour cells themselves in a range of solid cancers (including glioma, melanoma and some carcinomas), where it promotes invasion and metastasis.\n\nRadiolabelled cyclic RGD peptides (starting with 18F-Galacto-RGD, the first tracer used in patients, and followed by 68Ga-, 64Cu- and 99mTc-labelled RGD monomers, dimers and tetramers) bind αvβ3 and have been used in PET and SPECT imaging as a non-invasive biomarker of tumour angiogenesis, for patient selection ahead of anti-angiogenic therapy and for monitoring treatment response. Multimeric RGD constructs improve binding avidity through a polyvalency effect and show higher, more persistent tumour uptake than monomeric RGD.\n\nAs a target, αvβ3's strength is its sharp induction on angiogenic endothelium, giving genuine biological contrast between growing and quiescent vasculature. Its central weakness for imaging purposes is that αvβ3 is not exclusively expressed on new tumour vessels - it is also present on the tumour cells, on macrophages, and in non-malignant angiogenic settings such as atherosclerotic plaque and post-infarction myocardium - so a static PET signal cannot on its own distinguish tumour-cell expression from vascular expression, and genetic knockout studies suggest angiogenesis can still proceed without αvβ3, which has limited the target's use as a stand-alone therapeutic target despite active imaging interest.","asOf":"2026-09-22","links":[{"label":"PMC: PET imaging of integrin αvβ3 expression","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3086612/"},{"label":"PMC: clinical application of radiolabeled RGD peptides for PET imaging of angiogenesis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4679356/"},{"label":"PMC: RGD-binding integrins revisited - review of imaging targets including αvβ3","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8038522/"},{"label":"PMC: PET radiopharmaceuticals for imaging integrin expression","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4072020/"}],"tags":["angiogenesis","integrin","RGD peptide"],"related":["f-18","ga-68","tc-99m","cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A heterodimeric transmembrane adhesion receptor that binds RGD-motif extracellular matrix proteins such as vitronectin and fibronectin. It is minimally expressed on quiescent blood vessels but strongly upregulated on activated endothelial cells during tumour angiogenesis, and is also directly overexpressed on some tumour cells, where it promotes invasion and migration.","whereFound":["Tumour neovasculature (activated endothelial cells during angiogenesis): strongly upregulated versus quiescent vessels","Tumour cells directly in glioma, melanoma and some carcinomas: overexpression linked to invasion and metastasis","Atherosclerotic plaque and post-myocardial-infarction myocardium: upregulated on macrophages and activated endothelium, a non-oncological imaging application","Quiescent normal vasculature: low or absent expression"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/integrin-avb3/"}
{"id":"cck2-receptor","kind":"target","name":"CCK2 receptor (gastrin receptor)","aka":["CCK2R","CCK-B receptor","gastrin receptor"],"tldr":"A docking site for the hormone gastrin, found at very high numbers on medullary thyroid cancer cells. Minigastrin-like radioactive drugs can bind it to find or treat that cancer, though they also light up the stomach because the same receptor lines it normally.","summary":"CCK2R is a G-protein-coupled receptor for the hormones gastrin and cholecystokinin, expressed physiologically in the gastric mucosa where it regulates acid secretion, and in parts of the central nervous system. It is overexpressed at very high incidence and density in medullary thyroid carcinoma (MTC) - historically detected indirectly through the pentagastrin stimulation test - and also occurs in a substantial minority of small-cell lung cancers, astrocytomas, stromal ovarian cancers, gastrointestinal stromal tumours and some gastroenteropancreatic neuroendocrine tumours.\n\nRadiolabelled analogues of minigastrin, which retains the C-terminal receptor-binding tetrapeptide sequence (Trp-Met-Asp-Phe-NH2) common to gastrin and CCK, have been developed for both imaging (111In-, 99mTc-, or 68Ga-labelled minigastrin analogues, including Demogastrin 2 and MGS5) and therapy (90Y- or 177Lu-labelled minigastrin, such as 177Lu-PP-F11N). In patients with metastatic MTC, CCK2R-targeted imaging has detected more lesions than somatostatin receptor imaging, reflecting the low SSTR expression typical of MTC.\n\nAs a target, CCK2R's strength is very high density (over 90% of MTCs) and no competing standard-of-care radiotracer. Its central weakness, which has so far limited therapeutic use, is that the stomach expresses CCK2R physiologically and receives a comparable or higher radiation dose than the tumour with agonist-based minigastrin analogues, making the stomach dose-limiting; kidney and bone-marrow toxicity have also constrained early therapy trials, and receptor antagonist-based ligands (for example those built on nastorazepide) are being explored as an alternative with potentially better tumour-to-stomach ratios.","asOf":"2026-09-22","links":[{"label":"PMC: radiolabeled CCK/gastrin peptides for imaging and therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3205271/"},{"label":"JNM: CCK2 receptor agonist 177Lu-PP-F11N for medullary thyroid carcinoma therapy - dosimetry","url":"https://jnm.snmjournals.org/content/61/4/520"},{"label":"PMC: cholecystokinin-2 receptor targeting with radiolabeled peptides (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7116483/"},{"label":"Theranostics: nastorazepide-based CCK2R antagonist radioligands","url":"https://www.thno.org/v16p8447.htm"}],"tags":["neuroendocrine","thyroid","GPCR"],"related":["thyroid","sclc","ga-68","tc-99m","in-111","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A G-protein-coupled receptor for gastrin and cholecystokinin that physiologically regulates gastric acid secretion. It is overexpressed at very high density in medullary thyroid carcinoma and in a substantial minority of small-cell lung cancer, astrocytoma and other tumours, providing a target for minigastrin-based radiopeptides.","whereFound":["Medullary thyroid carcinoma: expressed at high density in over 90% of cases","Small-cell lung cancer: expressed in roughly half of cases","Astrocytoma, stromal ovarian cancer, gastrointestinal stromal tumours, some gastroenteropancreatic neuroendocrine tumours: variable expression","Normal gastric mucosa: physiological expression, the dose-limiting normal-tissue site for minigastrin therapy"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/cck2-receptor/"}
{"id":"upar","kind":"target","name":"uPAR (urokinase plasminogen activator receptor)","aka":["uPAR","PLAUR"],"tldr":"A protein that helps cancer cells break through surrounding tissue and spread. Higher amounts on a tumour are linked to more aggressive disease, and a PET tracer built on a small peptide can measure how much of it a tumour has.","summary":"uPAR is a glycosylphosphatidylinositol-anchored cell-surface receptor for urokinase-type plasminogen activator (uPA); the uPA/uPAR system focuses proteolytic activity (activation of plasmin, which degrades extracellular matrix) at the cell surface, driving tumour cell invasion, matrix remodelling and metastasis. uPAR overexpression is an established biomarker of tumour aggressiveness across several common cancers, including prostate, breast, bladder and glioma, and correlates with independent prognostic information beyond PSA and Gleason score in prostate cancer.\n\nThe PET ligand 68Ga-NOTA-AE105 (and the earlier 64Cu-DOTA-AE105), based on the high-affinity peptide antagonist AE105, has been evaluated in first-in-human and phase 2 studies in prostate cancer, breast cancer, bladder cancer and glioma. In localised prostate cancer, tumour SUVmax on 68Ga-NOTA-AE105 PET correlated significantly with Gleason score (Spearman ρ = 0.55), and a SUVmax cut-off achieved 96% sensitivity for detecting Gleason score ≥3+4, raising the possibility of uPAR PET reducing the number of repeat biopsies needed in active surveillance. In glioma, uPAR-PET uptake was associated with worse overall and progression-free survival.\n\nAs a target, uPAR's strength is a genuine link to tumour aggressiveness and metastatic potential across multiple tumour types, giving it prognostic as well as localising value. Its main limitation to date is that all published clinical PET data come from small studies run predominantly by one research group, so multicentre validation is still needed, and no uPAR-targeted therapeutic radioligand has reached clinical use.","asOf":"2026-09-22","links":[{"label":"JNM: uPAR PET/MRI (68Ga-NOTA-AE105) and Gleason score correlation in prostate cancer","url":"https://jnm.snmjournals.org/content/62/3/354"},{"label":"PMC: PET imaging of uPAR in prostate cancer (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5118403/"},{"label":"JNM: first-in-human study of 68Ga-NOTA-AE105 for uPAR PET imaging","url":"https://jnm.snmjournals.org/content/58/3/379"},{"label":"EJNMMI Research: phase 2 trial of 68Ga-NOTA-AE105 uPAR PET in glioma, survival correlation","url":"https://ejnmmires.springeropen.com/articles/10.1186/s13550-024-01164-9"}],"tags":["invasion","prostate cancer","prognostic biomarker"],"related":["prostate","nct06474806","ga-68","cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PLAUR","biology":"A GPI-anchored cell-surface receptor for urokinase-type plasminogen activator that focuses proteolytic activity at the cell surface, activating plasmin to degrade extracellular matrix and drive tumour invasion and metastasis. Its overexpression is an established biomarker of tumour aggressiveness in prostate, breast, bladder cancer and glioma.","whereFound":["Prostate cancer: uPAR expression correlates with Gleason score and aggressiveness","Glioma: uPAR-PET uptake associated with tumour grade and worse survival","Breast cancer and urinary bladder cancer: uPAR overexpression linked to invasive and metastatic potential","Normal tissue: low background expression, contributing to good image contrast"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/upar/"}
{"id":"mesothelin","kind":"target","name":"Mesothelin (MSLN)","aka":["MSLN"],"tldr":"A protein normally found only on the thin lining of the chest and abdomen, but made in large amounts by mesothelioma and by most pancreatic and many ovarian cancers. Because healthy organs barely make it, it is an attractive handle for antibody-based imaging and treatment.","summary":"Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface glycoprotein whose normal expression is restricted to mesothelial cells lining the pleura, pericardium and peritoneum. Its physiological function is not fully established, but it binds CA-125/MUC16, an interaction implicated in the peritoneal spread of ovarian cancer, and its overexpression has been linked to activation of NF-κB, MAPK and PI3K signalling that promotes proliferation, invasion and resistance to apoptosis.\n\nMesothelin is essentially absent from normal pancreas but is expressed in close to 100% of pancreatic ductal adenocarcinomas and virtually all epithelioid (though not sarcomatoid) mesotheliomas, and in a substantial majority of ovarian carcinomas (particularly serous subtype) and roughly half of lung adenocarcinomas, giving a wide tumour-to-normal-tissue contrast that has made it a target for antibody-drug conjugates (for example DMOT4039A/anetumab), immunotoxins (SS1P, LMB-100), CAR-T therapy and radiolabelled antibodies. 89Zr-labelled anti-mesothelin antibody immunoPET (for example 89Zr-MMOT0530A) has visualised pancreatic and ovarian cancer lesions in patients, with higher mean tumour SUVmax in ovarian than pancreatic lesions, plausibly reflecting the dense desmoplastic stroma that limits antibody penetration in pancreatic tumours. A thorium-227-labelled anti-mesothelin antibody-chelator conjugate (BAY2287411) has been tested in a first-in-human alpha-therapy trial in mesothelin-expressing tumours.\n\nAs a target, mesothelin's strength is a genuinely restricted normal-tissue expression pattern combined with near-universal expression in several hard-to-treat cancers. Its main limitations are that, as an antibody target, achieving good tumour penetration in stroma-rich tumours such as pancreatic adenocarcinoma is harder than in mesothelioma or ovarian cancer, and mesothelin is also shed from the cell surface into blood and ascites, which can act as an antigen sink for circulating antibody-based agents.","asOf":"2026-09-22","links":[{"label":"PMC: mesothelin-targeted cancer immunotherapy (expression table across tumour types)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2265108/"},{"label":"PMC: mesothelin as a biomarker for targeted therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6708176/"},{"label":"Clinical Cancer Research: immunoPET with anti-mesothelin antibody (89Zr-MMOT0530A) in pancreatic and ovarian cancer","url":"https://aacrjournals.org/clincancerres/article/22/7/1642/121738/ImmunoPET-with-Anti-Mesothelin-Antibody-in"},{"label":"MDPI Cancers: mesothelin as an immunotherapeutic target, including BAY2287411 thorium-227 conjugate","url":"https://www.mdpi.com/2072-6694/14/6/1550"}],"tags":["mesothelioma","pancreatic cancer","ovarian cancer","antibody target"],"related":["zr-89","th-227"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MSLN","biology":"A GPI-anchored cell-surface glycoprotein normally restricted to mesothelial cells lining the pleura, pericardium and peritoneum, whose interaction with CA-125/MUC16 has been implicated in the peritoneal spread of ovarian cancer. It is overexpressed in nearly all pancreatic ductal adenocarcinomas and epithelioid mesotheliomas and in most serous ovarian carcinomas, while normal organ parenchyma is negative.","whereFound":["Malignant pleural mesothelioma (epithelioid subtype): expressed in essentially all cases, absent in sarcomatoid mesothelioma","Pancreatic ductal adenocarcinoma: expressed in close to 100% of cases, absent in normal pancreas and chronic pancreatitis","Ovarian cancer (mainly serous subtype): expressed in roughly 70-100% of cases","Lung adenocarcinoma: expressed in a substantial minority of cases","Normal tissue: limited to mesothelial cells of pleura, pericardium and peritoneum"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/mesothelin/"}
{"id":"her3","kind":"target","name":"HER3 (ERBB3)","aka":["ERBB3","erb-b2 receptor tyrosine kinase 3"],"tldr":"A receptor on the surface of most lung cancer cells that helps tumours resist treatment. Drugs aimed at it exist, but measuring how much of it a tumour carries has so far failed to predict who benefits.","summary":"HER3 is a member of the epidermal growth factor receptor family with impaired intrinsic kinase activity, signalling instead through heterodimerisation with HER2 and EGFR and driving the PI3K-AKT pathway. It is widely expressed in epithelial cancers and is upregulated after EGFR tyrosine-kinase inhibitor treatment, which is why it became a target for antibody-drug conjugates in EGFR-mutant lung cancer. One published series reported HER3 expression in 83% of non-small cell lung cancers, with overexpression in 42% of a 45-patient cohort, more often than HER2.\n\nThe target's problem is measurement, not prevalence. Reviews state that there are no validated HER3 immunohistochemistry assays and no standardised scoring thresholds for predicting benefit, and the sponsor's own biomarker analyses of patritumab deruxtecan report no relationship between efficacy and HER3 protein expression by immunohistochemistry. An mRNA-based alternative developed by the SOLTI group found activity across a wide range of ERBB3 expression, again suggesting limited predictive value.\n\nFor molecular imaging this matters directly. Three antibody PET tracers have been built against HER3 (64Cu-patritumab, 89Zr-GSK2849330 and 89Zr-lumretuzumab) and all three belong to therapeutic programmes that were discontinued or lost momentum; in one published study no correlation between tumour uptake and ex-vivo immunohistochemistry could be determined. A single imaging trial is currently recruiting, 89Zr-patritumab deruxtecan at the Netherlands Cancer Institute with Daiichi Sankyo, on the rationale that HER3 expression can be assessed non-invasively including at sites that are difficult to biopsy.","asOf":"2026-09-23","links":[{"label":"HER3 expression in non-small cell lung cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"},{"label":"No relationship between HER3-DXd efficacy and HER3 immunohistochemistry, Nature Communications 2024","url":"https://www.nature.com/articles/s41467-024-50056-y"},{"label":"No validated HER3 assays or scoring thresholds (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12758208/"},{"label":"NCT06222489: 89Zr-patritumab deruxtecan PET/CT","url":"https://clinicaltrials.gov/study/NCT06222489"}],"tags":["adc-target","resistance","lung"],"related":["her2","opp-her3-imaging-crossover","cu-64","zr-89"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB3","hgnc":"HGNC:3431","ensembl":"ENSG00000065361","uniprot":"P21860","entrez":"2065","biology":"A receptor tyrosine kinase of the EGFR family with negligible intrinsic catalytic activity, which signals by heterodimerising with HER2 or EGFR to activate PI3K-AKT. Its expression rises after EGFR inhibition, making it a mechanism of acquired resistance as well as a target.","whereFound":["Non-small cell lung cancer: reported in 83% of cases, with overexpression in 42% of one 45-patient cohort","Breast cancer, including after endocrine and HER2-directed therapy","Colorectal and other epithelial cancers","Upregulated in tumours progressing on EGFR tyrosine-kinase inhibitors"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"nsclc","pct":83,"measure":"immunohistochemistry, any expression, published series","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"}],"route":"/targets/her3/"}
{"id":"cldn18-2","kind":"target","name":"Claudin-18.2","aka":["CLDN18.2","claudin 18 isoform 2","CLDN18"],"tldr":"A protein that seals the gaps between stomach lining cells. It stays on many stomach cancers as they spread, and two approved treatments are given only to patients whose biopsy shows it.","summary":"Claudin-18 splice variant 2 is a tight-junction protein of the gastric mucosa whose epitope becomes accessible on tumour cells as normal tissue architecture breaks down, making it an unusually tractable target in a cancer with few. It is the selection biomarker for zolbetuximab, approved in the US, EU, Japan and China for CLDN18.2-positive, HER2-negative gastric and gastro-oesophageal junction adenocarcinoma, and in June 2026 China approved satricabtagene autoleucel, a CLDN18.2 CAR-T, in the same biomarker-defined population.\n\nPositivity depends entirely on where the threshold is set. Across 4,507 patients screened for the SPOTLIGHT and GLOW trials, 38.4% were positive at the label threshold of moderate-to-strong membranous staining in at least 75% of tumour cells, and the sponsor reports approximately 35% positivity in Chinese patients with advanced disease. Selection is performed with the VENTANA CLDN18 (43-14A) RxDx assay.\n\nThe assay's failure mode is sampling, and it has been quantified. Against whole-tumour-section ground truth a single representative biopsy gave 58.8% sensitivity, rising to 76.5% with six to eight biopsies, and a minimum of six endoscopic biopsies was needed to keep false negatives acceptably low; 18% of tumours were discordant between the primary and a matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate at 91% overall accuracy. That is the gap three Chinese groups are now trying to close with PET: 68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L) each have a published first-in-human pilot of 11 to 17 patients.","asOf":"2026-09-23","links":[{"label":"CLDN18.2 positivity across pooled SPOTLIGHT and GLOW screening","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"Single-biopsy sensitivity against whole-section truth, Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"Multi-laboratory ring trial of CLDN18.2 immunohistochemistry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"First-in-human CLDN18.2 PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"label":"Gastric cancer biomarker testing review, naming the approved companion assay","url":"https://www.cancerbiomed.org/content/22/3/212"}],"tags":["adc-target","car-t-target","companion diagnostic","gastric"],"related":["opp-cldn18-2-imaging-gastric","her2","ga-68","i-124"],"indications":["gastric-oesophageal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CLDN18","hgnc":"HGNC:2039","ensembl":"ENSG00000066405","uniprot":"P56856","entrez":"51208","biology":"A tight-junction protein restricted to gastric mucosa in healthy tissue, whose extracellular loop becomes exposed on malignant cells when epithelial polarity is lost. Expression is retained in metastases often enough to make it a systemic therapeutic target.","whereFound":["Gastric and gastro-oesophageal junction adenocarcinoma: 38.4% positive at the 75%-of-cells threshold across 4,507 screened patients","Pancreatic adenocarcinoma, at lower frequency","Normal gastric mucosa, where the epitope is not accessible to antibodies"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"gastric-oesophageal-cancer","pct":"38.4","measure":"moderate-to-strong membranous staining in at least 75% of tumour cells, pooled SPOTLIGHT and GLOW screening","source":"https://link.springer.com/article/10.1007/s10120-024-01518-1"}],"route":"/targets/cldn18-2/"}
{"id":"alpha-synuclein","kind":"target","name":"Alpha-synuclein","aka":["a-synuclein","SNCA","alpha synuclein aggregates"],"tldr":"The protein that clumps inside brain cells in Parkinson's disease and related conditions. Nobody can yet see those clumps in a living person, which is why these diseases are still diagnosed by watching the patient.","summary":"Alpha-synuclein is a small presynaptic protein whose misfolded, aggregated forms define the synucleinopathies: Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Unlike amyloid and tau, which both have approved PET agents, no small molecule targeting misfolded alpha-synuclein has been approved by the FDA as a PET radiopharmaceutical, and the inability to quantify these aggregates in vivo limits accurate clinical diagnosis across the whole group.\n\nThe target is hard for physical reasons. The aggregates are intracellular and, in Parkinson's disease, present at far lower density than cortical amyloid plaques, and the protein has several conformational strains. The most advanced tracer, [18F]ACI-12589 from AC Immune, demonstrated this precisely in a 42-participant study published in Nature Communications in 2023: binding statistically separated multiple system atrophy patients from healthy controls and from other neurodegenerative disorders, with clear signal in cerebellar white matter and middle cerebellar peduncles, but showed limited binding in Parkinson's disease despite binding post-mortem Parkinson's tissue.\n\nThe competing measurement has already succeeded. Seed amplification assays on cerebrospinal fluid are reported at 87.7% sensitivity and 96.3% specificity for Parkinson's disease in the PPMI cohort, with a pooled meta-analysis across biomatrices at 0.86 and 0.92. What those assays cannot do is localise or quantify pathology, or measure whether a drug reduced it, and they are markedly less reliable in multiple system atrophy. That residual is where an imaging agent would have to earn its place.","asOf":"2026-09-23","links":[{"label":"[18F]ACI-12589 first-in-human, Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"label":"No approved small-molecule alpha-synuclein PET agent","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13121216/"},{"label":"Alpha-synuclein cannot currently be assessed accurately in vivo","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8466155/"},{"label":"Seed amplification assays: past, present and future roles","url":"https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm"},{"label":"Conference report: PET signal only in multiple system atrophy","url":"https://www.alzforum.org/news/conference-coverage/first-field-synuclein-pet-only-multiple-system-atrophy"}],"tags":["neurology","protein aggregate","unmet need"],"related":["tau-protein","amyloid-beta","opp-alpha-synuclein-pet-parkinsons","f-18"],"indications":["parkinsonian-syndromes"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SNCA","hgnc":"HGNC:11138","ensembl":"ENSG00000145335","uniprot":"P37840","entrez":"6622","biology":"A 140-amino-acid presynaptic protein involved in vesicle trafficking, which misfolds into beta-sheet-rich oligomers and fibrils that accumulate as Lewy bodies in neurons or as glial cytoplasmic inclusions in multiple system atrophy. The aggregates are intracellular, conformationally heterogeneous and, in Parkinson's disease, present at low density.","whereFound":["Parkinson's disease: Lewy bodies and Lewy neurites in neurons","Dementia with Lewy bodies: cortical Lewy pathology","Multiple system atrophy: glial cytoplasmic inclusions, the one form a tracer has so far detected in vivo","Not a cancer target; the imaging rationale is neurological"],"targetClass":"other","prevalence":[],"route":"/targets/alpha-synuclein/"}
{"id":"tpbg-5t4","kind":"target","name":"5T4 (trophoblast glycoprotein)","aka":["5T4","TPBG","5T4 oncofetal antigen","WAIF1"],"tldr":"A protein the placenta makes during pregnancy that many cancers switch back on while most healthy adult tissue does not. Antibody-drug conjugates against it have been tested in patients, and since 2024 the first radiolabelled versions have reached people in China.","summary":"5T4, encoded by TPBG (HGNC:12004), is a 72 kD heavily N-glycosylated membrane protein with leucine-rich repeats, first found by searching for surface molecules shared between human trophoblast and cancer cells. It is expressed by many different cancers but rarely in normal adult tissue, and its expression is linked to epithelial-mesenchymal transition, CXCL12/CXCR4 chemotaxis and a tumour-initiating phenotype (Stern and Harrop, Cancer Immunol Immunother 2017).\n\nThe target was validated clinically as an antibody-drug conjugate first. Pfizer's PF-06263507, an anti-5T4 IgG1 carrying monomethylauristatin-F, was given to 26 patients in a first-in-human trial (NCT01891669): the maximum tolerated dose was 4.34 mg/kg, ocular toxicity caused the dose-limiting events, and no objective responses were seen in patients who were not selected for 5T4 expression. In mesothelioma, 5T4 was expressed in 10 of 12 cell lines and most biopsies, and antibodies and ADCs against it internalise into lysosomes.\n\nRadiopharmaceutical work is recent and largely Chinese. A humanised single-domain antibody, [68Ga]Ga-NOTA-H006, went from camel immunisation to a pilot clinical study at Huashan Hospital, Fudan University, registered as NCT06162988, and mapped 5T4-positive lesions in patients with a mean effective dose of 0.034 mSv/MBq (EJNMMI 2025). An [18F]AlF-RESCA-H006 version was built for pancreatic adenocarcinoma, and a full-antibody theranostic pair, [89Zr]Zr-DFO-HB5 for imaging with [177Lu]Lu- and [161Tb]Tb-DOTA-HB5 for therapy, slowed tumour growth in two colorectal cancer xenograft models (J Med Chem 2026). A 2026 systematic review lists 5T4 with CEACAM5, TROP2, GPC3 and ROR1 as oncofetal surface antigens in advanced prostate cancer, including neuroendocrine and castration-resistant disease.\n\nThe open question is patient selection: the only ADC trial enrolled unselected patients and saw no responses, which is the gap a 5T4 imaging agent could close.","asOf":"2026-09-24","links":[{"label":"HGNC: TPBG gene record (HGNC:12004)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12004"},{"label":"He et al., EJNMMI 2025: [68Ga]Ga-NOTA-H006 preclinical and pilot clinical study (PMID 39377811)","url":"https://pubmed.ncbi.nlm.nih.gov/39377811/"},{"label":"Liang et al., J Med Chem 2026: [89Zr]Zr-DFO-HB5 immuno-PET and 161Tb vs 177Lu therapy in colorectal cancer (PMID 41984171)","url":"https://pubmed.ncbi.nlm.nih.gov/41984171/"},{"label":"Kong et al., Mol Pharm 2025: [18F]AlF-RESCA-H006 for pancreatic adenocarcinoma (PMID 40443260)","url":"https://pubmed.ncbi.nlm.nih.gov/40443260/"},{"label":"Shapiro et al., Invest New Drugs 2017: first-in-human anti-5T4 ADC PF-06263507 (PMID 28070718)","url":"https://pubmed.ncbi.nlm.nih.gov/28070718/"},{"label":"Harbi et al., EJNMMI Res 2026: oncofetal surface antigens in prostate cancer and radioligand targeting (PMID 41832388)","url":"https://pubmed.ncbi.nlm.nih.gov/41832388/"},{"label":"ClinicalTrials.gov NCT06162988: PET imaging of 68Ga-NOTA-H006 in malignancy","url":"https://clinicaltrials.gov/study/NCT06162988"}],"tags":["oncofetal antigen","antibody target","ADC-validated","China"],"related":["immuno-pet","zr-89","lu-177","tb-161","ga-68","radioligand-therapy","trop2","ceacam5","gpc3","f-18"],"indications":["colorectal-cancer","pancreatic-cancer","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TPBG","biology":"A heavily glycosylated leucine-rich-repeat membrane protein shared by trophoblast and cancer cells. It favours non-canonical over canonical Wnt signalling, potentiates CXCL12/CXCR4 chemotaxis and marks cells moving through epithelial-mesenchymal transition, and antibodies bound to it are internalised to lysosomes.","whereFound":["Placental trophoblast: the tissue in which it was discovered","Many carcinomas, including colorectal, pancreatic, lung and breast, with low expression in most normal adult tissue","Mesothelioma: 10 of 12 cell lines and most biopsy specimens positive, with variable intensity","Advanced prostate cancer, including neuroendocrine and castration-resistant forms (systematic review 2026)"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/tpbg-5t4/"}
{"id":"sortilin","kind":"target","name":"Sortilin (SORT1)","aka":["SORT1","Neurotensin receptor 3","NTSR3","Gp95"],"tldr":"A receptor that pulls molecules into cells and is found at high levels in several cancers, including ovarian, endometrial and triple-negative breast cancer. A peptide-drug conjugate against it is in a phase 1 trial, and the first radioactive pair (one version for scans, one for treatment) was published in 2026.","summary":"Sortilin, encoded by SORT1 (HGNC:11186), is a sorting receptor that carries bound ligands such as neurotensin and progranulin into cells. That internalising function is what drug developers exploit. Theratechnologies built TH19P01, a peptide that needs sortilin to enter cells, and conjugated it to docetaxel as TH1902 (sudocetaxel zendusortide). In their preclinical work, high sortilin expression correlated with shorter survival in triple-negative breast cancer, more than 75% of clinically annotated ovarian and endometrial tumours showed high sortilin by immunohistochemistry, and TH1902 outperformed unconjugated docetaxel in xenografts without causing neutropenia. The phase 1 trial in advanced solid tumours, NCT04706962, started in March 2021 and is listed as active, not recruiting.\n\nThe radiopharmaceutical side is new. In March 2026 a Peking University group labelled the anti-sortilin antibody latozinemab to make [89Zr]Zr-DFO-latozinemab for PET and [177Lu]Lu-DOTA-latozinemab for therapy. Melanoma tissue showed high sortilin (mean H-score 189.79); the PET agent gave high-contrast tumour images peaking at 72 hours; the lutetium conjugate reached 39.08% injected dose per gram in tumour at 72 hours; and 11.1 MBq significantly slowed tumour growth. The authors describe it as the first sortilin-directed theranostic pair.\n\nWhat is missing is anything between a full antibody with multi-day kinetics and the peptide carrying a chemotherapy payload: no small-molecule or peptide sortilin radioligand, and no human imaging data, has been published.","asOf":"2026-09-24","links":[{"label":"HGNC: SORT1 gene record (HGNC:11186)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11186"},{"label":"Gao et al., J Med Chem 2026: 89Zr/177Lu radioimmunoconjugates targeting SORT1 (PMID 41773941)","url":"https://pubmed.ncbi.nlm.nih.gov/41773941/"},{"label":"Currie et al., Cancers 2022: TH1902 against sortilin-positive ovarian and endometrial cancers (PMID 35454785)","url":"https://pubmed.ncbi.nlm.nih.gov/35454785/"},{"label":"Demeule et al., Cancer Sci 2021: TH1902 for sortilin-positive triple-negative breast cancer (PMID 34314556)","url":"https://pubmed.ncbi.nlm.nih.gov/34314556/"},{"label":"ClinicalTrials.gov NCT04706962: TH1902 in patients with advanced solid tumours","url":"https://clinicaltrials.gov/study/NCT04706962"}],"tags":["internalising receptor","peptide-drug conjugate","theranostic pair"],"related":["peptide-drug-conjugate","zr-89","lu-177","immuno-pet","radioimmunotherapy","breast-triple-negative"],"indications":["breast-triple-negative"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SORT1","biology":"A type I membrane sorting receptor of the VPS10P family that binds neurotensin, progranulin and other ligands and carries them into the cell, which makes it an internalising gateway for conjugated drugs or radionuclides.","whereFound":["Ovarian and endometrial cancer: high expression in more than 75% of clinically annotated tumours (Theratechnologies immunohistochemistry series)","Triple-negative breast cancer: high expression associated with shorter survival, particularly with nodal metastases","Melanoma: high expression on tissue microarray (mean H-score 189.79) and upregulated in transcriptional data across several cancers","Normal brain and other tissues, where it traffics neurotrophins and lysosomal cargo"],"targetClass":"surface-antigen","prevalence":[],"route":"/targets/sortilin/"}
{"id":"bradykinin-b1-receptor","kind":"target","name":"Bradykinin B1 receptor (B1R)","aka":["B1R","BDKRB1","BKR1","B1BKR"],"tldr":"A receptor that healthy tissue barely makes but inflammation and many cancers switch on. Gallium-68 and fluorine-18 peptides built from B1R-blocking drugs give sharp PET images in mice, but no B1R tracer has been given to a patient.","summary":"The bradykinin B1 receptor, encoded by BDKRB1 (HGNC:1029), is a G-protein-coupled receptor that is overexpressed in a variety of cancers while being essentially absent from healthy tissue, which is what first drew imaging groups to it.\n\nMost of the published radiochemistry comes from BC Cancer in Vancouver. In a 2015 Journal of Nuclear Medicine study, three gallium-68-labelled peptides derived from the B1R antagonists B9858 and B9958 bound the receptor with nanomolar affinity (Ki 1.1 to 16.0 nM), cleared through the kidneys, and at one hour showed only kidneys, bladder and B1R-positive tumours on PET; the best, 68Ga-P04158 and 68Ga-Z02090, reached 19.6 and 14.4% injected dose per gram in tumour. The same group then made 68Ga- and 18F-labelled derivatives of the more peptidase-stable antagonist R954, with tumour uptake around 8.5 to 9.3% injected dose per gram at one hour. Those studies used cells engineered to express human B1R. In 2024 a Showa Pharmaceutical University group showed that an indium-111 R954 derivative also tracks B1R expressed naturally in glioblastoma cells, with uptake that followed B1R levels and was blocked by unlabelled R954.\n\nA search of ClinicalTrials.gov on 24 September 2026 found no registered B1R imaging or therapy trial. The gaps are a first-in-human study and evidence of which human tumours carry enough receptor to image or treat.","asOf":"2026-09-24","links":[{"label":"HGNC: BDKRB1 gene record (HGNC:1029)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1029"},{"label":"Lin et al., J Nucl Med 2015: three 68Ga-labelled [des-Arg10]kallidin derivatives for B1R PET (PMID 25745086)","url":"https://pubmed.ncbi.nlm.nih.gov/25745086/"},{"label":"Kuo et al., Mol Pharm 2017: 68Ga- and 18F-labelled R954 derivatives for B1R PET (PMID 28094956)","url":"https://pubmed.ncbi.nlm.nih.gov/28094956/"},{"label":"Shukuri et al., Pharmaceuticals 2024: 111In-R954 derivative detects endogenous B1R in glioblastoma xenografts (PMID 39065752)","url":"https://pubmed.ncbi.nlm.nih.gov/39065752/"}],"tags":["GPCR","peptide receptor","preclinical only","unmet need"],"related":["ga-68","f-18","in-111","pet","glioblastoma","grpr"],"indications":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"BDKRB1","biology":"An inducible G-protein-coupled receptor for des-Arg kinins. It is barely expressed in healthy tissue but upregulated by inflammation and in many tumours, and antagonist peptides such as B9858, B9958 and R954 bind it with nanomolar affinity, which is the basis of the radiolabelled derivatives.","whereFound":["A variety of cancers, with limited or no expression in healthy tissue (BC Cancer radiochemistry series)","Glioblastoma cell lines: U87MG expresses more than U251MG, and radiotracer uptake follows that difference","Inflamed tissue, where expression is induced"],"targetClass":"other","prevalence":[],"route":"/targets/bradykinin-b1-receptor/"}
{"id":"dlg4-psd95","kind":"target","name":"DLG4 (PSD-95)","aka":["PSD-95","PSD95","SAP90","postsynaptic density protein 95","DLG4"],"tldr":"The main scaffold protein on the receiving side of brain synapses. Losing synapses tracks memory decline in Alzheimer's disease, but today's synapse PET scans only see the sending side (SV2A). No tracer for PSD-95 has been published, so the receiving side cannot yet be imaged.","summary":"DLG4 (HGNC:2903) encodes postsynaptic density protein 95, the scaffold that anchors glutamate receptors in the postsynaptic density of excitatory synapses. Synapse loss is an early event in Alzheimer's disease and is closely linked to cognitive decline, and PSD-95 is one of the proteins that falls. In post-mortem brain from the Banner Sun Health Research Institute, PSD-95 was lower in every region studied in Alzheimer's dementia than in controls without dementia (not significant in the hippocampus), and PSD-95 levels correlated with tangle and plaque density and with Mini Mental State Examination scores. In cerebrospinal fluid, a Massachusetts General Hospital study of two cohorts (178 and 156 people) found PSD-95 raised in Alzheimer's disease but not specific to it.\n\nSynaptic density PET today images the presynaptic vesicle protein SV2A with tracers such as 11C-UCB-J, used for example to follow synapse loss in animal models. A PubMed search on 24 September 2026 for PSD-95 or DLG4 together with PET, SPECT, radioligand or radiotracer returned 17 records, and none described a radioligand that binds PSD-95 itself.\n\nThat absence is the point of this record. PSD-95 is an intracellular scaffold rather than a receptor, so a tracer would need to cross the blood-brain barrier and the cell membrane and bind a protein-protein interaction domain, which is harder than binding a vesicle protein. The unmet need is a postsynaptic counterpart to SV2A PET that could separate loss of receiving sites from loss of transmitting sites.","asOf":"2026-09-24","links":[{"label":"HGNC: DLG4 gene record (HGNC:2903)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2903"},{"label":"Serrano et al., Int J Mol Sci 2024: presynaptic and postsynaptic proteins against pathology in Alzheimer's disease (PMID 38542104)","url":"https://pubmed.ncbi.nlm.nih.gov/38542104/"},{"label":"Kivisäkk et al., Alzheimers Res Ther 2022: PSD-95, SNAP-25 and neurogranin in CSF (PMID 35461266)","url":"https://pubmed.ncbi.nlm.nih.gov/35461266/"},{"label":"PubMed search used for the absence statement: PSD-95/DLG4 with PET, SPECT, radioligand or radiotracer","url":"https://pubmed.ncbi.nlm.nih.gov/?term=%28%22PSD-95%22%5Btiab%5D+OR+PSD95%5Btiab%5D+OR+DLG4%5Btiab%5D%29+AND+%28PET%5Btiab%5D+OR+radioligand%5Btiab%5D+OR+radiotracer%5Btiab%5D+OR+radiolabeled%5Btiab%5D+OR+radiolabelled%5Btiab%5D+OR+SPECT%5Btiab%5D%29"}],"tags":["neurology","synaptic density","no tracer yet","unmet need"],"related":["alzheimers-disease","amyloid-beta","tau-protein","pet","c-11"],"indications":["alzheimers-disease"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"DLG4","biology":"A membrane-associated guanylate kinase scaffold in the postsynaptic density of excitatory synapses. Its PDZ domains bind NMDA-receptor subunits and other partners, so its level is a proxy for the number of postsynaptic sites.","whereFound":["Excitatory synapses throughout the brain, concentrated in the postsynaptic density","Reduced across cortical regions in Alzheimer's dementia in post-mortem brain","Detectable in cerebrospinal fluid, raised in Alzheimer's disease and in some inflammatory, vascular and other neurodegenerative conditions"],"targetClass":"other","prevalence":[],"route":"/targets/dlg4-psd95/"}
{"id":"dota-chelation","kind":"technology","name":"DOTA chelation","aka":["DOTA","1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid"],"tldr":"DOTA is a small ring-shaped molecule that grips a radioactive metal atom tightly inside its cage, so the metal stays attached to the drug instead of drifting off into the body.","summary":"DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is a twelve-membered tetraaza macrocycle with four pendant carboxylate arms that together provide an octadentate (four nitrogen, four oxygen) cage for trivalent and some divalent radiometals. Complex formation proceeds through a diprotonated intermediate in which the metal sits outside the macrocyclic cavity, coordinated only to the four acetate arms; the rate-determining step is loss of the last ring-nitrogen proton, which lets the metal drop into the fully encapsulated, kinetically inert 'in-cage' geometry. Once formed at room temperature the complex does not revert, but formation itself is slow and usually needs heating (often 80-95°C) and, for large ions such as Ac3+, is inefficient because DOTA's cavity is sized for smaller lanthanide-like ions.\n\nThis chemistry underpins the majority of clinically used radiometal agents: 68Ga- and 177Lu-DOTATATE/DOTATOC, 90Y- and 177Lu-DOTA-conjugated peptides, and experimental 225Ac and 213Bi constructs. Its main practical strengths are extreme in vivo kinetic inertness (once formed, the metal essentially never leaves under physiological conditions) and a very large body of manufacturing and regulatory precedent. Its main limitations are the elevated temperature and time needed for labelling, which complicates heat-sensitive biomolecules such as antibodies, and its comparatively poor match to large ions like Ac3+, which has driven the search for alternative chelators such as macropa.","asOf":"2026-09-22","links":[{"label":"Price & Orvig, Chem Soc Rev 2014: Matching chelators to radiometals for radiopharmaceuticals","url":"https://doi.org/10.1039/C3CS60304K"},{"label":"One ring to bind them all? Review on DOTA complexes with medically relevant radiometals","url":"https://www.research.unipd.it/handle/11577/3611078"},{"label":"Mechanism and energetics of 90Y-DOTA complexation (J. Am. Chem. Soc. 1999)","url":"https://pubs.acs.org/doi/10.1021/ja983706q"},{"label":"Metal Chelating Agents for Medicinal Radionuclides (UBC open thesis, background on DOTA kinetics)","url":"https://open.library.ubc.ca/media/stream/pdf/24/1.0392203/4"}],"tags":["chemistry","chelator"],"related":["macropa-chelation","sarcophagine-chelation","radioligand-dosimetry","prrt","targeted-alpha-therapy","ga-68","lu-177","ac-225","y-90","bi-213"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production","radiopharmacy-network"],"notes":[],"principle":"A twelve-membered tetraaza macrocycle with four pendant carboxylate arms wraps around a metal ion, first binding it loosely outside the ring cavity, then, as the last ring-nitrogen proton is lost, letting the metal drop fully inside the cage to form an octadentate, kinetically inert complex that does not release the metal under physiological conditions.","strengths":[],"limitations":[],"since":"1980s (macrocyclic chelator chemistry); adapted to radiometals through the 1990s-2000s","route":"/technologies/dota-chelation/"}
{"id":"macropa-chelation","kind":"technology","name":"Macropa chelation","aka":["H2macropa","bp18c6"],"tldr":"Macropa is a newer ring-shaped molecule built specifically to grip large radioactive metal atoms, such as the alpha-emitter actinium-225, quickly and at room temperature, which older molecules like DOTA cannot do well.","summary":"Macropa (N,N'-bis[(6-carboxy-2-pyridyl)methyl]-4,13-diaza-18-crown-6) is an 18-membered diaza-crown-6 macrocycle with two pendant picolinate arms, first reported by Thiele et al. in 2017. Unlike DOTA, whose rigid octadentate cavity favours small lanthanide-sized ions, macropa shows 'reverse size selectivity': it binds large ions (Ac3+, Pb2+, La3+, Ra2+) markedly more tightly than small ones, matching Ac3+'s large 1.12 Å ionic radius. In side-by-side testing, macropa complexed essentially all of a 26 kBq 225Ac spike within 5 minutes at room temperature at submicromolar ligand concentration, whereas DOTA complexed only around 10% under the same conditions and required 80°C to go to completion.\n\nBifunctional derivatives (macropa-NCS) have been conjugated to antibodies (trastuzumab, the GPC3-targeting antibody codrituzumab/GC33) and to the PSMA-targeting small molecule RPS-070, and the resulting 225Ac complexes were stable for 7-8 days against human serum and excess La3+ challenge. Rigidified analogues (H2BZmacropa, H2BZ2macropa) trade some thermodynamic stability for improved synthetic access. Macropa also complexes 212Pb, 133La, 213Bi, 223Ra and 224Ra with varying efficiency, making it one of two chelators (alongside DOTA) most discussed for 225Ac-based targeted alpha therapy as of 2026; it does not solve the separate daughter-recoil problem that follows 225Ac decay.","asOf":"2026-09-22","links":[{"label":"Thiele et al., Angew. Chem. Int. Ed. 2017: An eighteen-membered macrocyclic ligand for actinium-225 targeted alpha therapy","url":"https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/anie.201709532"},{"label":"Kadassery et al., Bioconjugate Chem 2022: H2BZmacropa-NCS, a bifunctional chelator for 225Ac TAT","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9362842/"},{"label":"Equilibrium thermodynamics of macropa complexes with radiopharmaceutical metals (Inorg. Chem. 2023)","url":"https://pubs.acs.org/doi/10.1021/acs.inorgchem.3c01983"},{"label":"Advancing chelation strategies for large metal ions for nuclear medicine (UC eScholarship dissertation)","url":"https://escholarship.org/content/qt8hr5w9j2/qt8hr5w9j2.pdf"}],"tags":["chemistry","chelator","alpha therapy"],"related":["dota-chelation","alpha-daughter-redistribution","targeted-alpha-therapy","ac225-psma","ac-225","ra-223","pb-212","bi-213","ra-224"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production"],"notes":[],"principle":"An 18-membered diaza-crown-6 macrocycle with two picolinate arms has a cavity sized for large metal ions, so it shows 'reverse size selectivity' and binds large ions such as Ac3+, Pb2+ and La3+ far more tightly and far faster (minutes, at room temperature) than it binds small lanthanide-sized ions, the opposite preference to DOTA.","strengths":[],"limitations":[],"since":"2017 (first report); bifunctional NCS derivative and antibody conjugates 2019-2022","route":"/technologies/macropa-chelation/"}
{"id":"sarcophagine-chelation","kind":"technology","name":"Sarcophagine chelation","aka":["Sar","cage amine chelator","MeCOSar"],"tldr":"Sarcophagine is a cage-shaped molecule that locks copper atoms inside so tightly that the copper cannot escape once the imaging or treatment dose is made, even inside the body.","summary":"Sarcophagine ('sar', 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) is a hexaazamacrobicyclic cage-amine ligand, developed originally by Sargeson and colleagues, whose fully encapsulating three-dimensional cage confers exceptional kinetic inertness on its copper(II) complexes. Because the copper ion is enclosed rather than merely chelated at a macrocycle rim, sarcophagine complexes form rapidly (typically 5-20 minutes) at room temperature across a broad pH range (4-9) and resist demetalation and reduction to Cu+ far more effectively than open-chain or single-ring chelators such as DTPA or NOTA. The bifunctional derivative MeCOSar (methyl-carboxylate sarcophagine) is the most widely used variant for peptide and antibody conjugation.\n\nSarcophagine chelation is the basis of the clinical 64Cu/67Cu-SARTATE and 64Cu/67Cu-SAR-bisPSMA agents and of numerous 64Cu-labelled antibody constructs (including sarcophagine-trastuzumab and sarcophagine-cetuximab conjugates for PET imaging), where head-to-head comparisons have shown less than 6% loss of 64Cu from sarcophagine-antibody conjugates in serum over 48 hours, matching or beating NOTA. A drawback of first-generation sarcophagines (SarAr) is that the residual positive charge on the copper-cage complex increases kidney retention of labelled antibody fragments; charge-modified analogues (AmBaSar, and dibromomaleimide-linked variants) reduce this off-target renal uptake while retaining the fast, room-temperature labelling that makes sarcophagines attractive for 64Cu (and increasingly 67Cu) theranostic pairs.","asOf":"2026-09-22","links":[{"label":"Development of multi-functional chelators based on sarcophagine for 64Cu chelation (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6270798/"},{"label":"Comparison of bifunctional chelators including sarcophagine for 64Cu-rituximab labelling (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4756438/"},{"label":"Potential theranostics of breast cancer with copper-64/67-sarcophagine-trastuzumab (Chem. Sci. 2025)","url":"https://pubs.rsc.org/en/content/articlehtml/2025/sc/d4sc06969b"},{"label":"IAEA: Copper-64 radiopharmaceuticals - production, quality control and clinical applications","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1961_web.pdf"}],"tags":["chemistry","chelator","copper-64"],"related":["dota-chelation","radioimmunotherapy","pretargeted-radioimmunotherapy","cu-64","cu-67"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production"],"notes":[],"principle":"A three-dimensional hexaazamacrobicyclic cage fully encloses a copper ion on all sides, rather than gripping it at a ring rim, so the metal cannot demetalate or be reduced away in vivo; the closed cage also lets complexation happen in minutes at room temperature across a wide pH range.","strengths":[],"limitations":[],"since":"1980s (cage-amine ligand chemistry by Sargeson); bifunctional MeCOSar-NHS for bioconjugation from mid-2000s","route":"/technologies/sarcophagine-chelation/"}
{"id":"pretargeted-radioimmunotherapy","kind":"technology","name":"Pretargeted radioimmunotherapy","aka":["PRIT","pretargeting"],"tldr":"Instead of attaching radioactivity directly to a slow-moving antibody, doctors first inject the antibody alone, let it find the tumour and clear from the blood over some days, then inject a small fast-clearing radioactive tag that clicks onto the antibody only where it has stuck to the tumour.","summary":"Pretargeted radioimmunotherapy decouples the tumour-targeting antibody from the radionuclide, injecting them separately so that they combine in vivo. The generic sequence is: (1) administer an unlabelled or non-radioactive antibody derivative that carries a bio-orthogonal handle; (2) wait, typically 24-72 hours, for the antibody to accumulate at the tumour and clear from the circulation; (3) inject a small, rapidly clearing radiolabelled ligand; (4) allow it to ligate specifically to the antibody handle at the tumour, while any unbound radioligand is excreted quickly, sharply reducing radiation exposure to blood, marrow and other normal tissue compared with a directly labelled antibody. Four mechanistic platforms have been developed historically: streptavidin-biotin, bispecific antibodies that bind both a tumour antigen and a radiolabelled hapten (including the clinically advanced anti-tumour x anti-HSG bispecific/IMP288 peptide-hapten system), complementary oligonucleotide hybridisation (including morpholino, MORF/cMORF, backbones), and bio-orthogonal click chemistry using the inverse electron-demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO).\n\nThe bispecific-antibody/hapten route has the most extensive clinical experience, including phase I optimisation trials in colorectal cancer and CD38-bispecific pretargeting in multiple myeloma and B-cell malignancies. Click-chemistry pretargeting is the most recent and modular approach: preclinical work with the huA33 colorectal antibody and 177Lu-DOTA-PEG-tetrazine achieved tumour activity concentrations of roughly 21% injected dose per gram at a 24-hour antibody-to-radioligand interval, with a calculated effective dose of about 0.054 mSv/MBq, and 'masking agents' that inactivate residual circulating TCO have been used to further sharpen the dosimetric profile. Limitations include the added logistical complexity of two sequential injections, the need for very fast blood clearance of the radioligand to avoid background dose, and, for click chemistry, in vivo stability of the TCO/tetrazine handles.","asOf":"2026-09-22","links":[{"label":"Pretargeted imaging and therapy (J Nucl Med 2017 mini-review)","url":"https://jnm.snmjournals.org/content/58/10/1553"},{"label":"Current landscape in clinical pretargeted radioimmunotherapy (PMC 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8882889/"},{"label":"Towards optimisation of click-mediated pretargeted radioimmunotherapy (Mol. Pharm. 2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7047588/"},{"label":"Pretargeting for imaging and therapy in oncological nuclear medicine (EJNMMI review 2017)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5824696/"}],"tags":["chemistry","radioimmunotherapy","click chemistry"],"related":["radioimmunotherapy","sarcophagine-chelation","b7h3","cd20","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["radioimmunotherapy","sarcophagine-chelation"],"notes":[],"principle":"The tumour-targeting antibody and the radionuclide are injected separately: the antibody carries a chemical handle and is given time to accumulate at the tumour and clear from blood, then a small, fast-clearing radiolabelled partner molecule is injected and binds specifically to the handle wherever the antibody has settled, while unbound radioligand is rapidly excreted.","strengths":[],"limitations":[],"since":"Concept introduced 1985 (Reardan et al.); first clinical bispecific-antibody trials from the early 1990s; IEDDA click-chemistry pretargeting from 2010","route":"/technologies/pretargeted-radioimmunotherapy/"}
{"id":"albumin-binder-ligands","kind":"technology","name":"Albumin-binder ligands","aka":["albumin-binding moiety","Evans blue conjugate","IPBA conjugate"],"tldr":"Attaching a small chemical 'hook' that grips the body's own albumin protein makes a radioactive drug stay in the bloodstream for longer, so more of it reaches the tumour before it is cleared out through the kidneys.","summary":"Small-molecule and peptide radioligands (such as PSMA-617) are cleared from the blood within minutes to a few hours, which limits the fraction of injected activity that can diffuse into and bind tumour tissue before excretion. Conjugating an albumin-binding moiety, most commonly a truncated Evans blue (EB) dye derivative or 4-(p-iodophenyl)butyric acid (IPBA/IP), to the targeting ligand allows reversible, non-covalent binding to circulating serum albumin (biological half-life around 19 days), which extends the ligand's effective blood half-life from minutes to several hours without permanently trapping the radionuclide.\n\nIn preclinical work, Evans-blue-modified PSMA-617 (EB-PSMA-617) showed markedly extended blood retention compared with unmodified PSMA-617 and produced higher tumour uptake and greater therapeutic efficacy at lower administered activity in mouse models; a single low dose eliminated PSMA-positive tumours in one widely cited study. Albumin-binder chemistry generalises across chelator and radionuclide (86Y/90Y/177Lu-DOTA-EB-PSMA-617; 64Cu-PSMA-CM using an MPA albumin-binding moiety) and across targets (SSTR, GRPR ligands). The main design trade-off is pharmacokinetic: too strong an albumin interaction raises blood and normal-organ (especially bone marrow) dose and can worsen the therapeutic index, so linker length, albumin-binding affinity and total charge are tuned empirically for each ligand; increased kidney or hepatobiliary retention has also been reported for some albumin-binder designs and must be balanced against the gain in tumour dose.","asOf":"2026-09-22","links":[{"label":"Wang et al.: Single low-dose injection of Evans blue modified PSMA-617 radioligand therapy (Bioconjugate Chem 2018)","url":"https://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.8b00556"},{"label":"Albumin-binding PSMA ligands: implications for expanding the therapeutic window (J Nucl Med 2019)","url":"https://jnm.snmjournals.org/content/60/5/656"},{"label":"Development of an albumin-based PSMA probe with prolonged circulation, PMC 2020","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7773938/"}],"tags":["chemistry","pharmacokinetics","PSMA"],"related":["dota-chelation","radioligand-therapy","psma","cu-64","y-86","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["dota-chelation"],"notes":[],"principle":"A small chemical moiety with affinity for serum albumin (such as a truncated Evans blue dye or 4-(p-iodophenyl)butyric acid) is attached to the radioligand; it binds albumin reversibly, piggy-backing on the protein's long circulating half-life so the ligand stays in the bloodstream, and therefore available to bind the tumour, for hours instead of minutes.","strengths":[],"limitations":[],"since":"First albumin-binder radioligand conjugates reported around 2010; PSMA-EB conjugates from 2018","route":"/technologies/albumin-binder-ligands/"}
{"id":"radiohybrid-chemistry","kind":"technology","name":"Radiohybrid (rh) chemistry","aka":["rhPSMA","SiFA chemistry","silicon fluoride acceptor"],"tldr":"A radiohybrid molecule carries two possible attachment points, one for a fast PET-friendly radioactive fluorine tag and one for a radioactive metal used for treatment, so the imaging and treatment versions of the drug are chemically identical twins.","summary":"Radiohybrid (rh) ligands, developed by Wester and colleagues at the Technical University of Munich, combine a silicon-fluoride-acceptor (SiFA) group with a metal chelator (typically DOTA, DOTAGA or TRAP) within a single molecule. Only one of the two binding sites carries a radioactive isotope at a time: the SiFA silicon-fluorine bond can be radiolabelled with 18F by rapid isotopic exchange (19F/18F IE, complete in around 5 minutes at room temperature owing to a low, roughly 15.7 kcal/mol, activation barrier), while the chelator can instead be loaded with a radiometal such as 68Ga, 177Lu or 225Ac. This produces chemically near-identical diagnostic (18F/natMetal) and therapeutic (19F/radiometal) 'twins' with matched pharmacokinetics, avoiding the small structural differences that can arise between separately designed PET and radiometal tracers for the same target.\n\nThe lead compound 18F-rhPSMA-7 (and its isomer rhPSMA-7.3) showed imaging quality comparable to or better than 68Ga-PSMA-11 in clinical studies of low-PSA prostate cancer recurrence, and was developed into the FDA-approved diagnostic agent flotufolastat F-18. Laboratory-scale radiolabelling achieves radiochemical yields around 58% ± 9% and molar activities of 12-60 GBq/µmol within under 20 minutes, and the reaction is compatible with cartridge-based purification suited to automated GMP synthesis modules. The SiFA moiety's lipophilicity must be offset by adding a hydrophilic chelator or linker (or newer hydrophilic SiFA variants), and to date SiFA groups are the only chemistry used to build radiohybrids, so the concept has mainly been demonstrated for PSMA and minigastrin/CCK2R ligands rather than across the whole radioligand class.","asOf":"2026-09-22","links":[{"label":"Wurzer et al.: Radiohybrid ligands, a novel tracer concept exemplified by 18F- or 68Ga-labeled rhPSMA inhibitors (J Nucl Med 2020)","url":"https://jnm.snmjournals.org/content/61/5/735"},{"label":"PMC full text of the rhPSMA radiohybrid ligand paper","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7198388/"},{"label":"Recent advances in the clinical translation of silicon fluoride acceptor (SiFA) chemistry (Pharmaceuticals 2021)","url":"https://www.mdpi.com/1424-8247/14/7/701"}],"tags":["chemistry","PET","PSMA"],"related":["dota-chelation","psma-pet","f-18","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["dota-chelation","cyclotron-isotope-production"],"notes":[],"principle":"A single molecule carries two independent labelling sites, a silicon-fluoride-acceptor group that exchanges its stable fluorine-19 for radioactive fluorine-18 in minutes at room temperature, and a metal chelator; loading one site with a radioisotope while the other holds a non-radioactive isotope produces chemically matched diagnostic (18F) and therapeutic (radiometal) twins with identical pharmacokinetics.","strengths":[],"limitations":[],"since":"First reported 2019-2020 (rhPSMA); flotufolastat F-18 FDA approval 2025","route":"/technologies/radiohybrid-chemistry/"}
{"id":"mo99-tc99m-generators","kind":"technology","name":"Molybdenum-99/technetium-99m generators","aka":["Mo-99/Tc-99m generator","technetium cow"],"tldr":"A shielded column device lets hospitals 'milk' the world's most-used medical radioisotope, technetium-99m, fresh every day from a longer-lived parent isotope that is shipped to them from a reactor.","summary":"Technetium-99m (half-life about 6 hours, too short to transport far) is generated on demand from its parent molybdenum-99 (half-life about 66 hours) using column chromatography. Fission-produced 99Mo, as molybdate (MoO4^2-), is adsorbed onto an acid-washed alumina (Al2O3) column, typically 2-10 g of alumina, inside a lead-shielded housing. As 99Mo decays it forms pertechnetate (TcO4^-), which, carrying only a single negative charge, binds the alumina far more weakly than molybdate. Passing sterile 0.9% saline through the column selectively elutes sodium pertechnetate while molybdate stays bound, typically recovering more than 80% of the theoretical available 99mTc per elution ('milking'). Because 99mTc regenerates continuously from ongoing 99Mo decay, transient equilibrium is reached roughly 23-24 hours after the previous elution, which is when generators are normally milked for maximum yield.\n\nEluate quality is governed by US NRC 10 CFR 35.204 (99Mo breakthrough limit of 0.15 microcurie of 99Mo per millicurie of 99mTc at administration) and by aluminium-ion breakthrough limits (commonly under 10 microgram/mL), both checked at every elution because aluminium interferes with downstream cold-kit labelling, especially sulfur colloid. A generator is used for around one to two weeks before its 99Mo activity decays away, after which it is stored for roughly ten half-lives (about 28 days) before disposal as low-level waste. This generator underpins essentially all Tc-99m-based bone, cardiac, renal, hepatobiliary and sentinel-node imaging performed worldwide.","asOf":"2026-09-22","links":[{"label":"IAEA: Non-HEU production technologies for molybdenum-99 and technetium-99m","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1589_web.pdf"},{"label":"Mo99-Tc99m generator (StatPearls, NCBI Bookshelf)","url":"https://www.ncbi.nlm.nih.gov/sites/books/NBK565854/?report=printable"},{"label":"Tc-99m generator QC: Mo-99 breakthrough testing and NRC 10 CFR 35.204 limit","url":"https://www.diagnosticradphys.com/physicspulse/nuclear-medical-physics/tc-99m-generator-quality-control/"}],"tags":["generator","technetium","supply chain"],"related":["radionuclide-generators-kits","cold-kit-formulation","spect","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["research-reactor-isotope-production"],"notes":[],"principle":"The longer-lived parent isotope molybdenum-99 is bound tightly to an alumina column as molybdate; as it decays it forms pertechnetate, which carries a different charge and binds the alumina far more weakly, so flushing the column with saline selectively washes out the fresh technetium-99m daughter while the molybdenum parent stays behind to keep decaying and regenerating more daughter.","strengths":[],"limitations":[],"since":"Generator system developed at Brookhaven National Laboratory, 1957-1960s; in routine clinical use since the 1960s-70s","route":"/technologies/mo99-tc99m-generators/"}
{"id":"ge68-ga68-generators","kind":"technology","name":"Germanium-68/gallium-68 generators","aka":["68Ge/68Ga generator","GalliaPharm"],"tldr":"A compact column loaded with a long-lasting parent isotope lets a PET radiopharmacy produce fresh gallium-68, used in scans such as PSMA and DOTATATE PET, on demand without needing a cyclotron.","summary":"The 68Ge/68Ga generator holds parent germanium-68 (half-life 270.8-271 days) fixed on a solid-phase column, commonly TiO2, SiO2, SnO2 or hydrous stannic-oxide-type matrices, and yields daughter gallium-68 (half-life 67.7-68 minutes) by elution with dilute hydrochloric acid (typically 0.05-0.1 M HCl). Because 68Ge has a nine-month half-life, a single generator supplies clinically useful 68Ga for roughly a year, sufficient for hundreds of elutions, without requiring an on-site cyclotron. Regulatory eluate specifications (Ph. Eur. monograph 2464) require 68Ge breakthrough of no more than 0.001% of eluted activity; generators are typically eluted at least once per working day and pre-eluted with 5x4-10 mL washes after breaks of 72-96 hours to keep breakthrough within limits.\n\nEluate volumes (4-10 mL) are usually too dilute for direct high-specific-activity radiolabelling, so cation- or anion-exchange fractionation/concentration steps are commonly used before adding the eluate to a peptide precursor (for example DOTATATE or PSMA-11) at 90-95°C for 10-20 minutes to form the 68Ga complex. In routine operation, elution yields around 60-85% of theoretical maximum activity have been reported over hundreds of elutions per generator-year, with radiochemical purity of finished 68Ga-DOTATOC/68Ga-PSMA products typically exceeding 95-99%. The approach underlies most 68Ga-DOTATATE (NETSPOT-type kits) and 68Ga-PSMA-11 production worldwide and is complementary to cyclotron-based 68Ga production, which is increasingly used where generator throughput or supply is constrained.","asOf":"2026-09-22","links":[{"label":"EMA EPAR: GalliaPharm 68Ge/68Ga generator public assessment report","url":"https://www.ema.europa.eu/en/documents/assessment-report/galliapharm-epar-public-assessment-report_en.pdf"},{"label":"Good practices for 68Ga radiopharmaceutical production (EJNMMI Radiopharm. Chem. 2022)","url":"https://link.springer.com/article/10.1186/s41181-022-00180-1"},{"label":"The 68Ge/68Ga generator for enhancing productivity: multi-year performance data (PMC 2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13096388/"}],"tags":["generator","gallium-68","PET"],"related":["sstr-pet","psma-pet","cyclotron-isotope-production","radionuclide-generators-kits","ga-68","ge-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cold-kit-formulation"],"notes":[],"principle":"The nine-month half-life parent germanium-68 is fixed on a solid-phase column (titanium, tin or silicon oxide); eluting the column with dilute hydrochloric acid selectively washes off the freshly formed gallium-68 daughter while germanium-68 stays bound, so the same column keeps supplying fresh gallium-68 for about a year without needing a cyclotron on site.","strengths":[],"limitations":[],"since":"First 68Ge/68Ga generator systems developed in 1961; modern GMP-grade generators from the 2000s-2010s","route":"/technologies/ge68-ga68-generators/"}
{"id":"sr82-rb82-generators","kind":"technology","name":"Strontium-82/rubidium-82 generators","aka":["82Sr/82Rb generator","CardioGen-82","RUBY-FILL"],"tldr":"A generator produces a very short-lived radioactive potassium-like tracer on demand at the bedside, allowing a heart PET scan to be finished in minutes without needing an on-site cyclotron.","summary":"Rubidium-82 chloride is a potassium analogue used for PET myocardial perfusion imaging: its uptake into myocardium is proportional to blood flow via active Na+/K+-ATPase transport, with a single-capillary extraction fraction above 50%. Because 82Rb's physical half-life is only about 75 seconds, it cannot be shipped and must be produced at the point of use from its parent strontium-82 (half-life about 25-26 days), which is itself accelerator-produced by proton bombardment of a rubidium target and shipped to hospitals loaded on a generator column (commonly a hydrous stannic (tin) oxide matrix, 90-150 mCi/3.3-5.6 GBq of 82Sr at calibration). Elution with additive-free 0.9% saline yields rubidium-82 chloride injection; the very short daughter half-life allows the column to be re-eluted roughly every 10 minutes, supporting rapid sequential rest/stress imaging of many patients per day.\n\nCommercial systems (Bracco's CardioGen-82, approved in the US in 1989, and the newer Jubilant DraxImage RUBY-FILL) are used with dedicated infusion systems; the FDA label specifies adult rest/stress doses of 1,110-2,220 MBq (30-60 mCi) per component, imaging started 60-120 seconds after infusion, and mandatory testing of strontium-82 and strontium-85 breakthrough in the eluate. A generator remains usable for about 28-42 days depending on loaded activity. Comparative studies have found RUBY-FILL's 82Rb production efficiency roughly 7% higher than CardioGen-82's over a generator's working life, with both requiring daily quality assurance for breakthrough and elution accuracy.","asOf":"2026-09-22","links":[{"label":"FDA label: CardioGen-82 (rubidium Rb 82 generator), 2024 revision","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/019414s034lbl.pdf"},{"label":"Story of rubidium-82 and advantages for myocardial perfusion PET imaging (PMC 2015)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4566054/"},{"label":"Rubidium-82 generator yield and efficiency for PET perfusion imaging: comparative study (PMC 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7599151/"}],"tags":["generator","cardiac PET","rubidium-82"],"related":["pet-ct","quantitative-imaging-biomarkers","rb-82"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production","pet-ct"],"notes":[],"principle":"A generator column holds accelerator-produced strontium-82 (half-life about 25 days); eluting it with saline washes off the potassium-like daughter rubidium-82, whose 75-second half-life is far too short to ship, so it must be produced fresh at the bedside immediately before each heart scan and can be re-eluted roughly every 10 minutes.","strengths":[],"limitations":[],"since":"82Rb PET clinical studies from the 1980s; CardioGen-82 FDA approval 1989","route":"/technologies/sr82-rb82-generators/"}
{"id":"automated-synthesis-modules","kind":"technology","name":"Automated synthesis modules","aka":["TRACERlab","FASTlab","cassette-based radiosynthesizer"],"tldr":"A shielded robotic 'chemistry-in-a-box' machine mixes and purifies radioactive drugs behind thick walls, so staff never have to handle dangerous, highly radioactive liquids by hand.","summary":"Automated synthesis modules are enclosed, remotely operated instruments that carry out the radiolabelling reaction, purification and final formulation of PET and, increasingly, radiometal-based radiopharmaceuticals inside a hot cell, keeping the operator away from the high starting activities (multi-GBq to tens of Ci) typically used. Two broad module designs dominate: fixed-tubing systems (for example GE HealthCare's TRACERlab FX series) that give flexibility for method development and often include an integrated HPLC purification step, and cassette-based, single-use systems (for example FASTlab/FASTlab 2, Trasis AllinOne, Eckert & Ziegler modular-lab, Siemens Explora) that pre-package reagents and cartridges into a disposable cassette to reduce cross-contamination risk, shorten changeover time and ease GMP validation.\n\nA typical fully automated run traps cyclotron-delivered [18F]fluoride on an anion-exchange (QMA) cartridge, dries it, reacts it with the labelling precursor, then purifies the product by solid-phase extraction or HPLC and reformulates it for injection, all within roughly 15-45 minutes and commonly achieving radiochemical yields of 20-80% (radiotracer-dependent) and radiochemical purity above 95%. Modern platforms (e.g. FASTlab 2) also support radiometal-based syntheses (61/64Cu, 68Ga, 89Zr, 177Lu) on the same open, cassette-driven architecture. Because the chemistry, cleaning and dispensing sequence is programmed and logged, these modules are central to current Good Manufacturing Practice compliance and to reducing operator radiation dose, but they add capital cost and require dedicated cassette/reagent supply chains for each new tracer.","asOf":"2026-09-22","links":[{"label":"GE HealthCare: PET radiochemistry (FASTlab 2, TRACERlab product overview)","url":"https://www.gehealthcare.com/en-us/products/molecular-imaging/pet-radiochemistry"},{"label":"Automation of the radiosynthesis of six different 18F-labelled radiopharmaceuticals on the AllinOne module (PMC 2016)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5843816/"},{"label":"Simplified and highly-reliable automated production of [18F]FSPG for clinical studies, comparing TRACERlab and FASTlab (PMC 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10366059/"}],"tags":["manufacturing","PET","GMP"],"related":["hot-cells-and-shielding","pet-tracer-manufacturing","radiopharmaceutical-gmp-release","cyclotron-isotope-production","f-18","ga-68","cu-64","zr-89","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production","hot-cells-and-shielding"],"notes":[],"principle":"A programmable, remotely operated instrument inside a hot cell moves reagents through tubing or a pre-packed disposable cassette to trap the radioisotope, run the labelling reaction, purify the product by solid-phase extraction or HPLC, and reformulate it for injection, all without an operator's hands ever touching the high-activity solution.","strengths":[],"limitations":[],"since":"First-generation automated PET synthesis modules from the late 1990s-2000s; cassette-based systems (FASTlab, AllinOne) from the 2010s","route":"/technologies/automated-synthesis-modules/"}
{"id":"hot-cells-and-shielding","kind":"technology","name":"Hot cells and radiation shielding","aka":["hot cell","L-block","radiopharmacy shielding"],"tldr":"Radioactive drugs are made and handled behind thick walls of lead, tungsten or concrete inside sealed, negative-pressure boxes with built-in robot arms, so the radiation stays contained and staff outside stay safe.","summary":"A hot cell is a sealed, negative-pressure, lead- or lead-and-steel-shielded enclosure, commonly fitted with leaded-glass viewing windows, mechanical manipulator arms or gloved arm-ports, HEPA/charcoal filtration and an integrated dose calibrator, used to contain the synthesis, dispensing and quality control of radiopharmaceuticals at activities that would otherwise give unacceptable doses to staff. Shielding thickness is calculated from the photon energy of the radionuclides handled and the required dose-reduction factor, expressed in half-value layers (HVL) or tenth-value layers (TVL): a few millimetres of lead attenuates the 140 keV gammas of Tc-99m, while the 511 keV annihilation photons from F-18 or other positron emitters need much thicker, dedicated high-density shielding (lead HVL around 4-5 mm at 511 keV, tenth-value layer around 15 mm), and Lu-177 and Ac-225 handling for therapeutic radiopharmacy needs shielding tailored to their specific gamma and bremsstrahlung emissions.\n\nSource-side shielding (L-blocks, tungsten syringe and vial 'pig' shields, shielded transport containers) is generally more efficient than adding thickness to room walls, because it shields at the point of highest dose rate; tungsten's higher density (19.3 g/cm3 vs lead's 11.3 g/cm3) allows more compact shields where space near the operator is constrained, while lead remains the more economical choice for large, fixed room barriers. PET/F-18 radiopharmacies, I-131 therapy areas and Lu-177/Ac-225 handling suites each need shielding, ventilation and workflow (receipt, storage, dispensing, waste) sized to their specific radionuclide mix, and every hot cell installation is verified by a post-construction radiation survey against the physicist's calculated design goals before use.","asOf":"2026-09-22","links":[{"label":"Nuclear medicine hot lab design and safety, half-value-layer/tenth-value-layer shielding calculations","url":"https://www.diagnosticradphys.com/physicspulse/medical-health-physics/nuclear-medicine-hot-lab-design/"},{"label":"Design and construction of a radiochemistry laboratory: hot cell and shielded-trench case study (Pharmaceuticals 2024)","url":"https://www.mdpi.com/1424-8247/17/6/680"},{"label":"Robatel Technologies: radiopharmaceutical hot cells and casks, isotope-specific shielding overview","url":"https://robateltech.com/radiopharmaceutical-hot-cells-casks/"}],"tags":["radiation safety","manufacturing","GMP"],"related":["automated-synthesis-modules","radiopharmaceutical-gmp-release","gamma-probes-dose-calibrators","f-18","tc-99m","lu-177","ac-225","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["automated-synthesis-modules"],"notes":[],"principle":"Dense materials (lead, tungsten, concrete) placed between the radioactive source and people attenuate the emitted photons exponentially with thickness; the required thickness is calculated from the isotope's photon energy and the desired dose reduction, and is applied first at the source (syringe and vial shields, sealed hot-cell walls) because shielding close to a small source is far more efficient than shielding a whole room.","strengths":[],"limitations":[],"since":"Hot cell technology adapted from radiochemistry/nuclear industry practice through the 1960s-1980s; PET-specific high-density shielding from the 1990s-2000s","route":"/technologies/hot-cells-and-shielding/"}
{"id":"quantitative-spect","kind":"technology","name":"Quantitative SPECT","aka":["qSPECT","SPECT/CT quantification"],"tldr":"Modern gamma-camera scans can now be turned into maps of exactly how much radioactivity (in becquerels) sits in each part of the body, not just a picture, which is what lets doctors calculate a real radiation dose to a tumour or organ.","summary":"Conventional SPECT reconstructs relative counts per pixel; quantitative SPECT (qSPECT) converts those counts into absolute activity concentration, expressed in becquerels per millilitre (Bq/mL), by combining CT-based attenuation correction, scatter correction and collimator/detector resolution-recovery within an iterative reconstruction (typically ordered-subset expectation maximisation) and then applying a system-specific calibration factor. Attenuation correction requires a co-registered CT-derived attenuation map covering the full photon path length; scatter correction commonly uses dual- or triple-energy-window methods, with the choice of scatter-correction weighting shown to materially affect quantitative accuracy (activity underestimation of roughly 8-22% has been reported when using default rather than object-optimised scatter weighting). Cross-calibration between the gamma camera and an independent, traceable radionuclide (dose) calibrator, verified with a uniform cylindrical phantom, is required before patient images can be trusted quantitatively.\n\nThe 2022 EANM practice guideline for quantitative SPECT/CT recommends accuracy targets of 5-10% for diagnostic and about 5% for therapeutic radionuclides, and specifies phantom-based validation of recovery coefficients for small-volume accuracy (partial-volume effects remain the dominant source of negative bias for small lesions even with full correction). With these corrections in place, reconstructed qSPECT images at 24-iteration-equivalent settings can achieve activity-concentration accuracy within about 10% of true values for spheres down to roughly 11-12 mL. Quantitative SPECT is the imaging foundation for post-therapy dosimetry of 177Lu-, 90Y- and other radionuclide therapies and for deriving SUV-like metrics from SPECT rather than PET.","asOf":"2026-09-22","links":[{"label":"EANM practice guideline for quantitative SPECT-CT (EJNMMI 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9931838/"},{"label":"Optimisation of SPECT/CT imaging protocols for quantitative accuracy (EJNMMI Physics 2021)","url":"https://ejnmmiphys.springeropen.com/articles/10.1186/s40658-021-00405-3"},{"label":"Physical quantities useful for quality control of quantitative SPECT/CT (Nuclear Medicine Review 2021)","url":"https://journals.viamedica.pl/nuclear_medicine_review/article/download/NMR.2021.0020/63672"}],"tags":["dosimetry","imaging physics","SPECT"],"related":["spect-ct","monte-carlo-dosimetry","spect-dosimetry-workflow","radioligand-dosimetry","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["spect-ct"],"notes":[],"principle":"Raw SPECT counts are corrected, within the image reconstruction, for photon attenuation using a co-registered CT map, for scattered photons using multiple energy windows, and for the camera's own blurring; the corrected counts are then converted to absolute activity concentration (becquerels per millilitre) using a calibration factor measured against a traceable radionuclide calibrator and a phantom of known activity.","strengths":[],"limitations":[],"since":"CT-based attenuation correction on hybrid SPECT/CT from the early 2000s; formal EANM quantitative SPECT/CT guideline 2022","route":"/technologies/quantitative-spect/"}
{"id":"monte-carlo-dosimetry","kind":"technology","name":"Monte Carlo dosimetry","aka":["GATE","MCNP","voxel S-values"],"tldr":"Powerful computer simulations trace millions of individual particles of radiation as they fly through a virtual copy of a patient's body, giving the most detailed and realistic estimate of exactly how much radiation dose each organ and tumour actually receives.","summary":"Monte Carlo (MC) radiation-transport simulation is widely regarded as the reference-standard method for internal dosimetry in nuclear medicine. General-purpose codes such as MCNP6 and dedicated nuclear-medicine codes built on Geant4, principally GATE (Geant4 Application for Tomographic Emission) and GAMOS, simulate the full physics of radioactive decay and the subsequent transport and energy deposition of emitted photons, electrons and (increasingly) alpha particles through a voxelised representation of a patient's anatomy, derived from CT, and their measured or assumed radioactivity distribution, derived from SPECT or PET. Within the MIRD formalism, MC methods are used either to derive tabulated dosimetric quantities (the specific absorbed fraction, and the S-value, or mean absorbed dose per unit accumulated activity) for standard reference phantoms, or to run direct, patient-specific voxel-level simulations.\n\nValidation studies comparing GATE, GAMOS and MCNP6 for reference phantoms and clinical patient datasets have found strong cross-code agreement, typically within about 1-5% for self-organ S-values and within 10% (usually under 5%) for cross-organ absorbed fractions across a range of isotopes including F-18, Lu-177, I-131 and Y-90. Organ-level comparisons between GATE-derived and traditional MIRD/OLINDA S-value dosimetry have shown roughly 2% difference in total organ absorbed dose, though larger discrepancies (tens of per cent) can occur for individual cross-organ pairs. The principal drawback of direct MC simulation is computational cost, historically minutes to hours per patient dataset, which has motivated faster approximations (dose point kernel convolution, voxel S-value convolution) and, more recently, deep-learning surrogates trained on MC-generated dose maps for routine clinical throughput.","asOf":"2026-09-22","links":[{"label":"Advancing internal dosimetry in personalised nuclear medicine: MCNP6/GATE/GAMOS comparison (PMC 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12655809/"},{"label":"Internal dosimetry with the Monte Carlo code GATE: validation against ICRP/ICRU reference phantom (Phys Med Biol 2017)","url":"https://pubmed.ncbi.nlm.nih.gov/28182580/"},{"label":"Preclinical voxel-based dosimetry in theranostics: a review (PMC 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7198676/"},{"label":"Development and validation of RAPID, a Geant4-based patient-specific voxel dosimetry tool (PMC 2018)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5963670/"}],"tags":["dosimetry","simulation","physics"],"related":["quantitative-spect","spect-dosimetry-workflow","radioligand-dosimetry","ai-in-nuclear-medicine","f-18","lu-177","i-131","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["quantitative-spect"],"notes":[],"principle":"A computer simulates the random path of millions of individual emitted particles as they travel and deposit energy through a voxel-by-voxel digital copy of the patient built from CT (anatomy) and SPECT or PET (activity distribution), tracking enough particle histories that the statistical average of where the energy lands closely approximates the true physical radiation transport.","strengths":[],"limitations":[],"since":"GATE toolkit released 2004; validated for clinical-scale nuclear medicine dosimetry from the mid-2000s onward","route":"/technologies/monte-carlo-dosimetry/"}
{"id":"spect-dosimetry-workflow","kind":"technology","name":"SPECT dosimetry workflow for radionuclide therapy","aka":["post-therapy dosimetry","EANM dosimetry SOP"],"tldr":"After a radioactive treatment injection, patients are scanned two or three times over about a week so doctors can calculate exactly how much radiation dose the tumour and organs like the kidneys actually received, and adjust future doses if needed.","summary":"Clinical radionuclide-therapy dosimetry follows a standard sequence: sequential quantitative SPECT/CT (or hybrid planar-plus-SPECT/CT) imaging at multiple time points after administration, segmentation of source organs and tumours, fitting of time-activity curves to obtain the time-integrated activity in each region, and conversion to absorbed dose using either organ-level S-values (MIRD/OLINDA formalism) or voxel-level convolution/Monte Carlo methods. The EANM Dosimetry Committee's standard operational procedures, most recently the 2022 guideline for 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands, recommend using the same SPECT/CT system throughout a patient's dosimetry study, medium-energy collimators for 177Lu, iterative reconstruction with CT-based attenuation, scatter and (where available) collimator-response correction, and 60-120 projection angles at roughly 30-40 seconds per projection.\n\nFor kidney dosimetry, the guideline recommends three SPECT/CT acquisitions between 24 hours and 7 days after the first therapy cycle (with at least two days between the final two time points), reducing to a single acquisition at a matched time point for subsequent cycles, with the region of interest drawn to include the full renal cortex and medulla but exclude the pelvis. Tumour dosimetry follows a similar multi-time-point protocol, placing particular weight on a late imaging time point because tumour retention is typically slower than that of normal organs. A minimum of three time points is generally advised to characterise each exponential phase of the time-activity curve; two or three points at around 2, 4 and 24 hours are often sufficient for many source organs, but bone marrow and whole-body kinetics may need additional early sampling. Related standard operational procedures exist for 131I-mIBG neuroendocrine tumour therapy and for 90Y radioembolisation (99mTc-MAA pre-therapy and 90Y peri-therapy dosimetry).","asOf":"2026-09-22","links":[{"label":"EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled SSTR- and PSMA-targeting ligands (Eur J Nucl Med Mol Imaging 2022)","url":"https://link.springer.com/article/10.1007/s00259-022-05727-7"},{"label":"PMC full text of the EANM 177Lu dosimetry recommendations","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9015994/"},{"label":"EANM guidance document: dosimetry for first-in-human studies and phase 0/1 clinical trials (PMC 2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10957710/"},{"label":"EANM: Radionuclide therapy management technologist guide","url":"https://eanm.org/wp-content/uploads/2024/06/EANM22_TechGuide.pdf"}],"tags":["dosimetry","clinical protocol","PRRT"],"related":["quantitative-spect","monte-carlo-dosimetry","radioligand-dosimetry","prrt","lu177-radioligand-therapy","tc-99m","lu-177","i-131","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["quantitative-spect","monte-carlo-dosimetry"],"notes":[],"principle":"The patient is scanned with quantitative SPECT/CT at several defined time points after the therapy injection so that a time-activity curve can be fitted for each organ and tumour; integrating that curve gives the total number of decays in each region, which is then converted into an absorbed radiation dose using standardised organ- or voxel-level conversion factors.","strengths":[],"limitations":[],"since":"First EANM dosimetry SOPs (radioiodine) 2008; MIRD Pamphlet 26 on quantitative 177Lu SPECT dosimetry 2016; PRRT/PSMA-specific guideline 2022","route":"/technologies/spect-dosimetry-workflow/"}
{"id":"ai-in-nuclear-medicine","kind":"technology","name":"AI in nuclear medicine","aka":["deep learning PET/SPECT","aPROMISE"],"tldr":"Computer software trained on thousands of scans can now automatically outline tumours on PET and SPECT images in seconds instead of the 30-45 minutes it takes a doctor, though a specialist still checks the result.","summary":"Artificial intelligence, predominantly convolutional neural networks and related deep-learning architectures, is being applied across nuclear medicine and radioligand therapy for automated lesion detection and segmentation, tumour-burden quantification, image denoising and reconstruction, CT-free attenuation/scatter correction, and early-stage dose-prediction and toxicity models. In PSMA PET, deep-learning segmentation tools (for example the aPROMISE platform) have matched inter-radiologist agreement for prostate-gland segmentation (Dice similarity coefficient around 0.89 versus an inter-radiologist DSC of about 0.91) while completing a scan in roughly 15 seconds compared with 30-45 minutes for manual contouring, and a comparative reader study against a standard PACS viewer found similarly high intra- and inter-reader agreement with both systems against histopathology as the reference standard, with the AI tool automatically segmenting about 92% of consensus lesions.\n\nA 2026 structured narrative review across PSMA, somatostatin-receptor/PRRT, radioiodine and 90Y-radioembolisation platforms found the strongest direct evidence for AI-assisted segmentation, tumour-burden quantification and early dose-map prediction, but concluded that no platform yet has a prospectively validated, outcome-linked model for AI-guided treatment selection or activity prescription; independent, multicentre, external validation against dosimetric reference standards remains the key evidence gap. Test-retest repeatability studies of AI-derived PSMA tumour-volume metrics show acceptable reproducibility when the same tracer is used for both scans, but substantially wider limits when different PSMA tracers (for example 68Ga-PSMA-11 versus 18F-PSMA-1007) are compared, underscoring that AI outputs, like human-read metrics, are tracer- and protocol-dependent. Current consensus across systematic reviews is that AI should be used as an adjunct that improves efficiency and reproducibility, with expert nuclear medicine physician oversight remaining necessary given model 'black box' limitations and performance variability.","asOf":"2026-09-22","links":[{"label":"PSMA PET evaluation with a deep-learning platform compared with a standard viewer and histopathology (J Nucl Med 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/41101977/"},{"label":"Artificial intelligence across oncologic theranostics: evidence for patient stratification, dosimetry and adaptive radiopharmaceutical therapy (Front. Nucl. Med. 2026)","url":"https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2026.1935247/full"},{"label":"The value of artificial intelligence in PSMA PET: a pathway to improved efficiency and results, systematic review (2025)","url":"https://pubmed.ncbi.nlm.nih.gov/40444499/"},{"label":"Deep learning-based PSMA PET segmentation repeatability: test-retest analysis (2026)","url":"https://pubmed.ncbi.nlm.nih.gov/41166032/"}],"tags":["AI","imaging","PSMA"],"related":["radiomics","quantitative-imaging-biomarkers","psma-pet","monte-carlo-dosimetry","f-18","ga-68","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["quantitative-imaging-biomarkers","psma-pet"],"notes":[],"principle":"Neural networks trained on large sets of scans with expert-drawn reference contours learn to recognise the imaging patterns of disease directly from pixel data, so a new scan can be automatically segmented, quantified or flagged in seconds by pattern-matching against what the network learned, rather than a person tracing every lesion by hand.","strengths":[],"limitations":[],"since":"Deep-learning segmentation tools for PET/SPECT emerging from the mid-2010s; clinical deployment of platforms such as aPROMISE from the early 2020s","route":"/technologies/ai-in-nuclear-medicine/"}
{"id":"cold-kit-formulation","kind":"technology","name":"Cold kit formulation","aka":["technetium cold kit","lyophilised radiopharmaceutical kit"],"tldr":"Many everyday radioactive scan drugs come as a freeze-dried powder in a sealed vial; the hospital pharmacy just adds the freshly produced radioactive solution and the finished injectable drug forms in minutes, no chemistry lab required.","summary":"A 'cold kit' is a sterile, pyrogen-free, freeze-dried (lyophilised) vial containing a non-radioactive ligand together with a reducing agent (commonly stannous/tin(II) chloride for technetium chemistry), buffer to set the correct pH for labelling, and stabilisers or fillers. Reconstituting the kit with freshly eluted radionuclide, most often sodium [99mTc]pertechnetate from a molybdenum-99/technetium-99m generator, or 68Ga chloride from a germanium-68/gallium-68 generator, drives rapid complex formation, sometimes at room temperature, sometimes with brief heating (for example 20 minutes in a boiling water bath for some 99mTc-HYNIC peptide kits), yielding an injectable radiopharmaceutical without dedicated radiochemistry infrastructure. Because the cold components are pre-sterilised and sealed, the entire process is a closed, aseptic operation that can be performed safely within a standard hospital nuclear medicine pharmacy rather than a full synthesis laboratory.\n\nCold kits typically have long, refrigerated shelf lives (commonly 3-12 months at 2-8°C) prior to radiolabelling, but the reconstituted, radiolabelled product itself is usually stable and usable for only a few hours at room temperature. Established 99mTc cold kits cover bone (MDP/HDP), myocardial perfusion (MIBI, tetrofosmin), renal (DTPA, MAG3-type, DMSA), hepatobiliary (mebrofenin), lung perfusion (MAA), lymphoscintigraphy (tilmanocept, nanocolloid), and neuroendocrine (HYNIC-TOC/TATE) imaging. The same general approach, sometimes called 'cold kit labelling', has since been extended to 68Ga-radiopharmaceuticals (for example the FDA/EMA-approved Illuccix and Locametz PSMA-11 kits), reducing the specialised equipment needed for routine PET tracer production. In the US, compounding radiopharmaceuticals, including kit reconstitution outside licensed manufacturing, is governed by USP General Chapter <825>, which sets minimum standards for preparation, dispensing and repackaging and defines beyond-use dating that accounts for radionuclide half-life and radiolytic decomposition.","asOf":"2026-09-22","links":[{"label":"IAEA Technical Reports Series 466: Technetium-99m radiopharmaceuticals - manufacture of kits","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/trs466_web.pdf"},{"label":"Cold kit labeling: the future of 68Ga radiopharmaceuticals? (PMC 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8869247/"},{"label":"USP fact sheet: decisions on appeals to General Chapter <825> Radiopharmaceuticals","url":"https://www.usp.org/sites/default/files/usp/document/health-quality-safety/usp-decision-on-appeals-825-factsheet.pdf"}],"tags":["manufacturing","cold kit","technetium"],"related":["mo99-tc99m-generators","ge68-ga68-generators","radionuclide-generators-kits","sterile-fill-finish","illuccix","locametz","ga-68","tc-99m","mo-99","ge-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["mo99-tc99m-generators","ge68-ga68-generators"],"notes":[],"principle":"A vial of freeze-dried, sterile, non-radioactive ligand, reducing agent and buffer is reconstituted at the point of use simply by adding the freshly eluted radionuclide solution; the labelling chemistry then proceeds inside the sealed, closed vial without any dedicated synthesis equipment, yielding an injectable dose within minutes.","strengths":[],"limitations":[],"since":"99mTc cold kits in routine use since the 1970s; 68Ga cold kits (Illuccix, Locametz) FDA/EMA approved 2021","route":"/technologies/cold-kit-formulation/"}
{"id":"radiolabelling-quality-control","kind":"technology","name":"Radiolabelling quality control","aka":["radiochemical purity testing","radio-TLC","radio-HPLC"],"tldr":"Before any radioactive drug is given to a patient, a quick chemistry test checks that the radioactive atom is properly and completely attached to the drug molecule, rather than floating free, because free radioactivity goes to the wrong place in the body.","summary":"Radiochemical purity (RCP) is the proportion of a radiopharmaceutical's total radioactivity that is present in the intended, correctly labelled chemical form, and it is distinct from radionuclidic purity (correct radioisotope, free of parent or other radioactive contaminants such as 99Mo breakthrough) and chemical purity (non-radioactive contaminants such as aluminium ion breakthrough from a generator column). RCP is most commonly measured by instant thin-layer chromatography (iTLC or ITLC-SG): a small spot of the radiopharmaceutical is applied near the base of a silica-impregnated glass-fibre or paper strip, developed in a specified mobile phase, then either scanned with a radiochromatogram scanner or cut into segments and counted in a gamma counter or dose calibrator, with RCP calculated as the percentage of counts in the desired product peak versus total counts on the strip. Typical release specifications require RCP of at least 90-95%, with the exact limit, solvent system and strip type defined by the product's package insert, USP monograph or Ph. Eur. monograph, and a failing preparation must be rejected and not administered.\n\nHigh-performance liquid chromatography (radio-HPLC) offers finer chromatographic resolution and can detect degradation products from radiolysis that iTLC misses; one comparative study of 177Lu-PSMA found that reducing RCP by 50% (through induced radiolysis) reduced the labelled peptide's cell-binding capacity by 27%, and that only HPLC, not iTLC, identified the radiolysis peaks responsible, underscoring that the two methods are complementary rather than interchangeable (iTLC remains preferred for fast, sensitive detection of free/unbound radiometal at release, while HPLC is used for detailed impurity profiling and method validation). For alpha-emitter products such as 225Ac-labelled peptides, additional considerations apply, including waiting for radioactive equilibrium between 225Ac and its gamma-emitting daughters (213Bi, 221Fr) before iTLC readout, and confirming RCP by both radio-iTLC and radio-HPLC (typical release criteria of at least 95% by radio-iTLC).","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC: quality control methods for radiopharmaceuticals, including TLC/iTLC and HPLC procedures","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf"},{"label":"Radiolabeling and quality control of therapeutic radiopharmaceuticals: cross-validation of RCY/RCP by radio-TLC and radio-HPLC (PMC 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9636342/"},{"label":"BNMS/UKRG information resource: radiochemical purity systems of radiopharmaceuticals","url":"https://cdn.ymaws.com/www.bnms.org.uk/resource/resmgr/ukrg/resources/2021_information_resources_r.pdf"}],"tags":["quality control","GMP","chemistry"],"related":["cold-kit-formulation","radiopharmaceutical-gmp-release","automated-synthesis-modules","mo-99","lu-177","ac-225","bi-213"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cold-kit-formulation","automated-synthesis-modules"],"notes":[],"principle":"A small spot of the finished radiopharmaceutical is run on a chromatography strip or through an HPLC column, which physically separates the correctly labelled drug from any unbound or degraded radioactivity; counting how much radioactivity ends up in the product's peak versus everywhere else gives the percentage that is in the intended chemical form, which must clear a preset limit before the dose can be released for injection.","strengths":[],"limitations":[],"since":"Radiochemical purity testing standardised through pharmacopoeial monographs from the 1980s-1990s; current USP <821>/<825> and Ph. Eur. general chapters","route":"/technologies/radiolabelling-quality-control/"}
{"id":"alpha-daughter-redistribution","kind":"technology","name":"Alpha-emitter daughter redistribution ('free daughter' problem)","aka":["nuclear recoil effect","free daughter problem"],"tldr":"When an alpha-emitting radioactive drug decays inside the body, the recoil kick is so strong that the leftover radioactive fragment breaks loose from the drug and can drift to organs like the kidneys, causing side effects the original drug was never meant to cause.","summary":"Alpha decay releases so much energy that conservation of momentum imparts a substantial recoil to the daughter nucleus, typically on the order of 100-200 keV. This is roughly a thousand times larger than the energy of any chemical bond, so the daughter nuclide breaks free of its chelator or targeting vector essentially every time an alpha particle is emitted, regardless of how strong that chemical bond was. For actinium-225 (half-life 9.9 days), which decays through francium-221 (half-life 4.8 minutes), astatine-217 (33 ms) and bismuth-213 (45.6 minutes) before reaching stable bismuth-209, the recoiling daughters can travel through the bloodstream and redistribute to non-target tissue. Biodistribution studies of free 221Fr and 213Bi report rapid clearance from blood (only 1-6% injected dose per gram remaining by 15 minutes) accompanied by strong renal accumulation of both species (roughly 18-35% ID/g in the kidney at 5-15 minutes) and additional 221Fr uptake in the salivary glands and small/large intestine; free 213Bi released from an antibody-chelate conjugate distributes to kidney, urine and other organs in roughly 40:30:30 proportions in some series, and renal toxicity attributable to 213Bi is a recognised dose-limiting concern that has restricted several 225Ac clinical trials.\n\nLead-212 (half-life 10.64 hours) behaves differently because it decays by beta, not alpha, emission to its alpha-emitting daughter bismuth-212: beta-decay recoil energy (around 1 eV) is far too small to break a chelate bond on its own, but the sudden change in nuclear charge and valence-electron reorganisation on going from Pb2+ to Bi3+ still causes a substantial fraction, roughly 36% in one widely cited DOTA study, of 212Bi to dissociate from the chelator, and its 60.5-minute half-life gives it time to redistribute (chiefly to kidney, and to a lesser extent heart, pancreas and bone) before it decays further. Mitigation strategies under active investigation include using chelators specifically optimised for lead retention (PSC, TCMC/DOTAM) that markedly reduce 212Bi escape and redistribution compared with DOTA; using rapidly internalising targeting ligands so decay happens after the parent is already inside the target cell; encapsulating the parent radionuclide inside nanoparticles (liposomes, polymersomes, inorganic lattices such as LaPO4 or InPO4) sized to physically trap recoiling daughters, with reported retention of roughly 40-70% of 213Bi and 221Fr depending on carrier design; and localised (intratumoural) administration to reduce the opportunity for systemic redistribution. No approach fully eliminates the problem, and it remains one of the central unresolved chemistry challenges for 225Ac- and, to a lesser extent, 212Pb-based targeted alpha therapy.","asOf":"2026-09-22","links":[{"label":"Actinium-225/bismuth-213 as potential leaders for targeted alpha therapy: recoil and mitigation strategies (Cancers 2025)","url":"https://www.mdpi.com/2072-6694/17/18/3055"},{"label":"Actinium-225 targeted alpha particle therapy for prostate cancer: recoil, nephrotoxicity and mitigation approaches (Theranostics 2024)","url":"https://www.thno.org/v14p2969.htm"},{"label":"The in vivo fate of 225Ac daughter nuclides using polymersomes as a model carrier (PMC 2019)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6690960/"},{"label":"Biodistribution of free francium-221 and bismuth-213 in tumour-bearing mice (PMC 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12660422/"},{"label":"Preclinical evaluation of a lead-specific chelator (PSC) minimising 212Bi daughter redistribution (PMC 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9966725/"},{"label":"SECURE project review: clinical application and future potential of alpha-particle therapy, recoil section (Pharmaceuticals 2025)","url":"https://www.mdpi.com/1424-8247/18/10/1578"}],"tags":["alpha therapy","chemistry","toxicity"],"related":["targeted-alpha-therapy","macropa-chelation","alpha-nanogenerators","ac225-psma","alphamedix","ac-225","pb-212","bi-213"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["targeted-alpha-therapy","macropa-chelation"],"notes":[],"principle":"When an alpha particle is emitted, conservation of momentum kicks the leftover daughter nucleus with roughly 100-200 keV of recoil energy, about a thousand times more than the energy of any chemical bond, so the daughter atom is physically knocked out of its chelator cage regardless of how strong that chelator normally is, freeing it to travel through the bloodstream and accumulate in organs such as the kidney.","strengths":[],"limitations":[],"since":"Recognised as a dose-limiting mechanism since early 225Ac-antibody radioimmunotherapy studies in the 2000s; nanoparticle and internalising-ligand mitigation strategies from the 2010s onward","route":"/technologies/alpha-daughter-redistribution/"}
{"id":"krenning-score","kind":"term","name":"Krenning score","aka":[],"tldr":"A 0-to-4 scale doctors use to describe how strongly a tumour lights up on a somatostatin receptor scan, by comparing it with the normal liver and spleen. A higher score generally means the tumour is a good candidate for peptide receptor radionuclide therapy.","summary":"The Krenning score is a five-point visual grading system (0-4) developed for planar and SPECT imaging with 111In-pentetreotide (OctreoScan), which grades tumour uptake of a somatostatin receptor tracer against two internal reference tissues: normal liver (grades 1-3) and spleen or kidney (grade 4). Grade 0 is no uptake; grade 1 is uptake below liver; grade 2 is uptake equal to or slightly less than liver; grade 3 is uptake greater than liver; grade 4 is uptake greater than spleen or kidney. The NETTER-1 trial required tumour uptake at least equal to normal liver (Krenning grade 2 or above) for enrolment, and a score greater than 2 is the practical threshold most centres use when selecting patients for PRRT with lutetium-177 dotatate.\n\nThe score has been extrapolated to gallium-68 and copper-64 DOTATATE PET/CT as a \"modified Krenning score\", but the correlation between the original scintigraphy-derived score and the PET-derived score is limited: PET is more sensitive, is acquired around one hour after injection rather than 24 hours, and tends to grade the same lesion higher. For lesions larger than 2 cm the modified score is considered more reliable; centres should state which imaging method and which reference organ underlie a reported grade.\n\nThe score is lesion-level and visual rather than quantitative, so heterogeneous disease (some lesions with low uptake alongside others with high uptake) requires reporting each discordant lesion separately rather than a single summary number, since a single index-lesion grade can misrepresent overall receptor status across the body.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: Krenning score of neuroendocrine tumour uptake","url":"https://radiopaedia.org/articles/krenning-score-of-neuroendocrine-tumour-uptake?lang=us"},{"label":"Somatostatin receptor imaging and theranostics: current practice and future prospects (JNM/PMC, 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9364764/"}],"tags":["scoring system","SSTR imaging","PRRT eligibility"],"related":["ga68-dotatate","sstr-pet","prrt","itm-11","lutathera","neuroendocrine","netter-1","ga-68","in-111","cu-64","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging","route":"/terms/krenning-score/"}
{"id":"psma-rads","kind":"term","name":"PSMA-RADS (PSMA reporting and data system)","aka":[],"tldr":"A standard 1-to-5 scale that nuclear medicine doctors use to describe how likely a spot seen on a PSMA PET scan is to be prostate cancer, so different hospitals describe the same finding the same way.","summary":"PSMA-RADS version 1.0, proposed by Rowe, Pienta, Pomper and Gorin at Johns Hopkins in 2017-2018, is a structured reporting system for PSMA-targeted PET imaging modelled on other \"reporting and data systems\" such as BI-RADS. It assigns each lesion a category from 1 (benign, subdivided into 1A without uptake and 1B with uptake but known-benign) through 2 (likely benign, low-level uptake atypical for prostate cancer), 3A/3B/3C/3D (equivocal, warranting further work-up such as biopsy or 3-6 month follow-up imaging), 4 (intense uptake typical of prostate cancer but without a corresponding finding on conventional imaging) to 5 (intense uptake with a corresponding conventional-imaging finding, prostate cancer almost certainly present). Reports give up to five target lesions a PSMA-RADS category plus an overall scan score equal to the highest individual lesion score.\n\nInterobserver agreement studies on 18F-DCFPyL PET/CT found good-to-excellent agreement (intraclass correlation coefficients of 0.60-0.84 depending on lesion type), supporting its reproducibility across readers. A revised PSMA-RADS 2.0 has since been proposed, folding the 1A/1B split into a single benign category, allowing PSMA-RADS 3A/3B/3D lesions to be reclassified as 4 in patients with widespread metastatic disease, and adding a 5T subcategory for effectively treated metastases after systemic prostate cancer therapy.\n\nThe system is complementary to PSMA PET-guided treatment decisions (for example selecting patients for lutetium-177 or actinium-225 PSMA radioligand therapy) but is not itself a treatment-eligibility threshold; eligibility criteria used in trials such as VISION relied on separate PSMA-positivity rules.","asOf":"2026-09-22","links":[{"label":"Rowe SP, Pienta KJ, Pomper MG, Gorin MA. Proposal for a Structured Reporting System for PSMA-Targeted PET Imaging: PSMA-RADS Version 1.0. J Nucl Med 2018;59:479-485","url":"https://jnm.snmjournals.org/content/jnumed/59/3/479.full.pdf"},{"label":"Werner RA, et al. Interobserver Agreement for PSMA-RADS 1.0 on 18F-DCFPyL PET/CT. J Nucl Med (2018)","url":"https://jnm.snmjournals.org/content/jnumed/early/2018/09/06/jnumed.118.217588.full.pdf"},{"label":"PSMA-RADS: updated version 2.0 discussion (PMC, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11981304/"}],"tags":["reporting system","PSMA PET","structured reporting"],"related":["psma-pet","psma","ga68-psma-11","pylarify","pluvicto","prostate-mcrpc","vision","f-18","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging","route":"/terms/psma-rads/"}
{"id":"deauville-for-pet","kind":"term","name":"Deauville five-point scale for PET","aka":[],"tldr":"A simple 1-to-5 score doctors use on a PET scan of lymphoma to say whether treatment is working, by comparing how bright the tumour looks against two normal reference areas: the blood in the chest and the liver.","summary":"The Deauville five-point scale (also called the 5-point scale, 5PS) grades FDG uptake in each lymphoma lesion visually against two internal reference tissues: the mediastinal blood pool and the liver. Score 1 is no uptake above background; 2 is uptake at or below the mediastinal blood pool; 3 is uptake above the mediastinum but at or below the liver; 4 is uptake moderately higher than liver; 5 is uptake markedly higher than liver and/or new lesions. An additional X denotes new uptake felt unlikely to be lymphoma. Proposed in 2009 and incorporated into the 2014 Lugano classification for staging and response assessment, it is now the standard scale for FDG-avid nodal lymphomas including Hodgkin lymphoma and most non-Hodgkin subtypes.\n\nUnder Lugano, a complete metabolic response is a Deauville score of 1, 2 or 3 (with or without a residual mass) and no marrow involvement; a partial metabolic response is score 4 or 5 with reduced uptake from baseline; no metabolic response (stable disease) is score 4 or 5 unchanged; progressive metabolic disease is score 4 or 5 with increasing uptake or new FDG-avid lesions. Score 3 is generally treated as a good-prognosis complete response, except in de-escalation trials, where some protocols treat score 3 as an inadequate interim response to avoid undertreatment.\n\nThe scale's simplicity and reproducibility drove its adoption in trials such as RATHL, which used interim PET response to de-escalate or intensify treatment in advanced Hodgkin lymphoma. A residual mass greater than 2 cm alongside a Deauville 1-2 result at end of treatment has been associated with a higher relapse risk in diffuse large B-cell lymphoma in some series, illustrating that the scale is read alongside anatomic findings rather than in isolation.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: Deauville five-point scale","url":"https://radiopaedia.org/articles/deauville-five-point-scale?lang=us"},{"label":"Radiopaedia: Lugano classification (PET-CT treatment response)","url":"https://radiopaedia.org/articles/lugano-classification-pet-ct-treatment-response?lang=us"},{"label":"RATHL trial: adapted treatment guided by interim PET-CT in advanced Hodgkin lymphoma, NEJM 2016","url":"https://www.nejm.org/doi/10.1056/NEJMoa1510093"}],"tags":["response criteria","lymphoma","FDG PET"],"related":["fdg-pet","dlbcl","rathl","hd21","complete-response-term","suv"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging","route":"/terms/deauville-for-pet/"}
{"id":"tumour-to-background-ratio","kind":"term","name":"Tumour-to-background ratio (TBR)","aka":[],"tldr":"A simple number that says how much brighter a tumour looks on a scan compared with the normal tissue around it or nearby. A higher ratio makes a tumour easier to see and count.","summary":"Tumour-to-background ratio (TBR), also called tissue-to-background or lesion-to-background ratio, divides a measure of tracer uptake in a lesion (typically SUVmax or SUVpeak) by a measure of uptake in a reference region, which may be a fixed organ such as liver or blood pool, gluteal muscle, the contralateral normal tissue, or the tissue immediately surrounding the lesion (\"local TBR\"). Because PET and SPECT images are reconstructed and displayed with contrast-dependent scaling, TBR is a practical proxy for lesion conspicuity and is used both qualitatively (as a component of the Krenning score and PSMA-RADS) and quantitatively in response criteria.\n\nIn amino acid PET for brain tumours, the RANO/EANM/SNMMI/EANO consensus (PET RANO 1.0) defines PET-positive tumour as any voxel with uptake at least 1.6 times the mean background activity measured in a reference region of normal frontal lobe, and tracks change in TBRmax and TBRmean over time as response criteria (for example, an increase of 30% or more in TBRmax defines PET-based progression). The choice of reference tissue changes the number materially: a lesion's ratio to liver, muscle, and the immediately surrounding tissue can differ by an order of magnitude, so any reported TBR should state which reference region and which SUV metric were used.\n\nTBR is sensitive to technical factors including reconstruction algorithm, attenuation correction, and time after injection, so serial comparisons for treatment response are only valid when acquisition protocol is held constant.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: tissue to background ratio","url":"https://radiopaedia.org/articles/tissue-to-background-ratio?lang=us"},{"label":"PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0), Lancet Oncology group report","url":"https://escholarship.org/content/qt7480171k/qt7480171k_noSplash_75492753629cf0018dd0db00b41434a0.pdf"}],"tags":["quantitative imaging","SUV","response assessment"],"related":["suv","quantitative-imaging-biomarkers","krenning-score","psma-rads","fdg-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging","route":"/terms/tumour-to-background-ratio/"}
{"id":"fixed-versus-personalised-dosing","kind":"term","name":"Fixed versus personalised (dosimetry-guided) dosing","aka":[],"tldr":"Most radioactive cancer treatments today give every patient the same amount, on the same schedule, regardless of body size. Researchers are testing whether measuring how much radiation reaches a patient's kidneys and tumours, and adjusting the dose accordingly, works better and is safer.","summary":"Approved peptide receptor radionuclide therapy (lutetium-177 dotatate, Lutathera) and PSMA radioligand therapy (lutetium-177 vipivotide tetraxetan, Pluvicto) are both dosed as a fixed activity per cycle regardless of patient size: Lutathera as 7.4 GBq every 8 weeks for four cycles, the schedule used in NETTER-1, and Pluvicto similarly as a fixed per-cycle activity. This mirrors how most targeted small-molecule cancer drugs are dosed, but it ignores patient-to-patient variability in biodistribution, renal clearance and tumour burden, all of which change how much radiation different organs and tumours actually absorb from the same injected activity.\n\nDosimetry-guided (personalised) dosing instead measures absorbed dose to organs at risk (chiefly kidney and bone marrow) after each cycle, using post-therapy SPECT/CT or serial blood and imaging sampling, and adjusts the number of cycles or the activity of subsequent cycles to reach a pre-defined cumulative dose limit (commonly around 23 Gy to the kidney and roughly 2 Gy to bone marrow, thresholds extrapolated from external-beam radiotherapy experience). A single-centre Swedish phase 2 trial individualising the number of 177Lu-DOTATATE cycles by renal biological effective dose reported a 16% partial response rate, 66% stable disease, and a median progression-free survival of 29 months and overall survival of 47 months in 96 evaluable patients, comparable to or exceeding NETTER-1 in a similar population. The ongoing DUONEN phase 3 trial in Poland is comparing fixed 7.4 GBq dosing against several dosimetry-guided 177Lu/90Y regimens with per-cycle activity adjusted to organ dose.\n\nNo randomised trial has yet shown personalised dosing to be superior to the fixed NETTER-1/VISION schedules on a hard efficacy endpoint, and the nuclear medicine community has not agreed a single validated dosimetry methodology, which is why fixed dosing remains the regulatory-approved standard of care. The idea that dosimetry-personalised PRRT could replace four fixed cycles is an active research question rather than settled practice.","asOf":"2026-09-22","links":[{"label":"Sandström M, et al. Phase II trial: efficacy and safety of individualized, dosimetry-based 177Lu-DOTATATE (ILUMINET), Eur J Nucl Med Mol Imaging 2022","url":"https://link.springer.com/article/10.1007/s00259-022-05786-w"},{"label":"Haug AR. PRRT of neuroendocrine tumors: individualized dosimetry or fixed dose scheme? EJNMMI Res 2020","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7158965/"},{"label":"DUONEN trial: dosimetry-guided peptide receptor radionuclide therapy, Frontiers in Endocrinology 2025","url":"https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1716247/full"}],"tags":["dosimetry","PRRT","individualised therapy"],"related":["radioligand-dosimetry","prrt","itm-11","lutathera","pluvicto","idea-net-dosimetry-prrt","idea-total-body-pet-dosimetry","gray-unit","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"therapy","route":"/terms/fixed-versus-personalised-dosing/"}
{"id":"salivary-gland-toxicity","kind":"term","name":"Salivary gland toxicity (xerostomia) from PSMA radioligand therapy","aka":[],"tldr":"PSMA radioligand therapy can dry out the mouth because normal salivary glands pick up a small amount of the drug along with the tumour. It's very common but usually mild, and is one of the main reasons patients ask about the treatment beforehand.","summary":"Prostate-specific membrane antigen is expressed at low levels on normal salivary gland tissue as well as on prostate cancer cells, so PSMA-targeted radioligand therapies deliver an incidental radiation dose to the salivary glands. In the pivotal VISION trial of lutetium-177 vipivotide tetraxetan (Pluvicto), dry mouth (xerostomia) occurred in 39% of patients receiving Pluvicto plus best standard of care versus 0.5-1% on standard of care alone (any grade); no grade 3-4 xerostomia was reported in VISION. Dosimetry sub-studies found a mean salivary gland absorbed dose of roughly 0.5-0.6 Gy/GBq, which is towards the lower end of a wide reported range (0.5-1.9 Gy/GBq), and translates to roughly 25-30 Gy after a full six-cycle course at 7.4 GBq per cycle.\n\nThe FDA label for Pluvicto lists dry mouth among the most common adverse reactions (occurring in \\u226520% of patients) and specifies dose modifications for recurrent or higher-grade dry mouth: for grade 2, withhold until improvement and consider a 20% dose reduction; for grade 3, withhold and reduce by 20% to 5.9 GBq; recurrent grade 3 dry mouth after one dose reduction is grounds for permanent discontinuation. In the combined PSMAfore/VISION safety population reported in a later label update, dry mouth of any grade occurred in around 46-61% of patients, reflecting longer follow-up and pooled populations.\n\nManagement is largely supportive: hydration, sugar-free gum or lozenges to stimulate residual saliva, avoiding alcohol-based mouthwash and irritant foods, and monitoring for secondary dental disease, since dry mouth increases caries risk. Xerostomia typically improves gradually after treatment ends. External radioprotective strategies (external cooling, salivary gland-sparing infusion techniques) are under investigation but are not yet standard of care.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto (lutetium Lu 177 vipivotide tetraxetan), accessdata.fda.gov","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215833s021s024lbl.pdf"},{"label":"EMA: Pluvicto assessment report (EPAR)","url":"https://www.ema.europa.eu/en/documents/assessment-report/pluvicto-epar-public-assessment-report_en.pdf"},{"label":"[177Lu]Lu-PSMA-617 (Pluvicto): The First FDA-Approved Radiotherapeutic for mCRPC, PMC 2022","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9608311/"}],"tags":["adverse effect","PSMA therapy","quality of life"],"related":["pluvicto","lu177-psma-it","psma","prostate-mcrpc","vision","psmafore","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety","route":"/terms/salivary-gland-toxicity/"}
{"id":"renal-protection-amino-acids","kind":"term","name":"Renal protection with amino acid co-infusion","aka":[],"tldr":"Before a peptide receptor radionuclide therapy infusion, patients are given an IV drip of two amino acids, lysine and arginine, which reduces how much radioactivity the kidneys reabsorb and hold onto, protecting kidney function.","summary":"Radiolabelled peptides such as DOTATATE are filtered by the kidney and partly reabsorbed in the proximal tubule, where they can be retained long enough to deliver a clinically significant radiation dose; the kidney is the dose-limiting organ for peptide receptor radionuclide therapy. Co-infusing positively charged amino acids, most commonly a mixture of L-lysine and L-arginine, competitively blocks this tubular reabsorption. The joint IAEA/EANM/SNMMI practical guidance on PRRT describes protocols using 25 g lysine plus 25 g arginine (a 50 g total \"cocktail\") diluted in 1-2 litres of normal saline and infused over about 4 hours, started 30-60 minutes before the radiopeptide and continued for at least 3-4 hours afterwards; some centres extend protection over 2-3 days post-therapy for additional renal sparing.\n\nPublished reductions in renal absorbed dose from amino acid co-infusion range from roughly 9% to 65% depending on amino acid dose, infusion duration, and how long protection is continued after therapy, with a commonly cited average reduction of around 40%. Higher lysine doses (for example 75 g) reduce renal uptake further but cause more side effects such as nausea and vomiting, so 25 g lysine plus 25 g arginine is regarded as the standard trade-off. Hyperkalaemia, nausea and vomiting are the main side effects of the amino acid infusion itself, and hyperosmotic solutions should be avoided in patients with cardiac insufficiency because of the risk of volume overload and electrolyte disturbance.\n\nDespite renal protection, long-term creatinine clearance loss of roughly 3-4% per year has been reported after 177Lu-DOTATATE (compared with a steeper roughly 7% per year after the older 90Y-DOTATOC), and PRRT is generally avoided in patients with a glomerular filtration rate below 30-40 mL/min. A large single-institution retrospective series of over 1,200 patients receiving amino acid-protected PRRT found no clear evidence of long-term nephrotoxicity, though prospective, randomised confirmation across centres is limited. Alternatives such as arginine-only infusion or Gelofusine/succinylated gelatin, and newer approaches such as para-aminohippurate (PAH) co-infusion, are being studied as ways to reduce side effects while preserving nephroprotection.","asOf":"2026-09-22","links":[{"label":"IAEA, EANM, SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours, PMC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3622744/"},{"label":"Long-term Nephrotoxicity after PRRT: Myth or Reality, PMC 2024","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10758070/"},{"label":"Bergsma H, et al. Safety and Efficacy of Para-Aminohippurate Coinfusion for Nephroprotection, J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/65/6/931"}],"tags":["nephroprotection","PRRT","supportive care"],"related":["prrt","itm-11","lutathera","neuroendocrine","cytopenias","gray-unit","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety","route":"/terms/renal-protection-amino-acids/"}
{"id":"myelosuppression-after-rlt","kind":"term","name":"Myelosuppression after radioligand therapy","aka":[],"tldr":"Radioactive cancer treatments that circulate through the blood also irradiate bone marrow, so blood counts (red cells, white cells, platelets) can drop. Doctors check blood counts regularly and pause or reduce treatment if counts fall too far.","summary":"Because radioligand therapies circulate systemically before binding their target, bone marrow receives incidental irradiation and can develop dose-related cytopenias. In the VISION trial of lutetium-177 vipivotide tetraxetan (Pluvicto) for metastatic castration-resistant prostate cancer, grade 3-4 laboratory abnormalities occurred in 15% of patients for decreased haemoglobin, 9% for decreased platelets, 7% for decreased leukocytes and 4.5% for decreased neutrophils; grade 3-4 pancytopenia occurred in 1.1% including two fatal events, and four myelosuppression-related deaths were reported in total (from intracranial or subdural haemorrhage associated with thrombocytopenia, sepsis with neutropenia, and bone marrow failure). In the earlier-line PSMAfore and PSMAddition trials, grade 3-4 rates were generally lower (for example, grade 3-4 decreased haemoglobin 7% and 4.3% respectively), consistent with less marrow reserve in more heavily pretreated VISION-era patients.\n\nThe Pluvicto label requires complete blood counts before and during treatment and specifies dose modifications for myelosuppression: withhold for grade 2, and withhold plus reduce the dose by 20% (to 5.9 GBq/160 mCi) for grade 3 or higher, with permanent discontinuation for recurrent grade 3 or higher myelosuppression after one dose reduction. Lymphopenia is the most frequent laboratory abnormality overall, reported in over 80-90% of patients at any grade in pooled analyses, reflecting the radiosensitivity of lymphocytes.\n\nFor peptide receptor radionuclide therapy with lutetium-177 dotatate, grade 3-4 haematological toxicity is less frequent, reported around 9-13% in cohort series, generally reversible, and less common than with the historical 90Y-labelled somatostatin analogues. Risk factors for more severe myelosuppression across radioligand therapies include extensive bone marrow involvement by tumour, prior chemotherapy or external beam radiotherapy, and impaired baseline renal function, since slower renal clearance prolongs the radiopharmaceutical's circulation time and marrow exposure.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto, dosage modifications and adverse reactions","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215833s021s024lbl.pdf"},{"label":"Novartis Pluvicto prescribing information (Warnings and Precautions: myelosuppression)","url":"https://www.novartis.com/us-en/sites/novartis_us/files/pluvicto.pdf"},{"label":"Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic CRPC (expanded access programme vs VISION), J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/65/11/1740"}],"tags":["adverse effect","haematology","radioligand therapy"],"related":["pluvicto","vision","psmafore","cytopenias","thrombocytopenia","anaemia","bone-marrow","prrt","lutathera","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety","route":"/terms/myelosuppression-after-rlt/"}
{"id":"extravasation-radiopharmaceutical","kind":"term","name":"Radiopharmaceutical extravasation","aka":[],"tldr":"Sometimes an injected radioactive tracer or treatment leaks into the tissue around the vein instead of going into the bloodstream. For scanning tracers this usually just affects image quality; for treatment doses it can occasionally injure the skin and needs prompt attention.","summary":"Extravasation is the inadvertent leakage of an injected radiopharmaceutical into the tissue surrounding the injection site instead of the vein. For diagnostic tracers labelled with 99mTc, 123I, 18F or 68Ga, extravasation is common but rarely causes tissue injury; a systematic review of more than 3,000 reported diagnostic extravasations found fewer than 0.1% caused symptoms requiring clinical follow-up, and none of the 99mTc/123I/18F/68Ga cases needed intervention. Its main practical consequence for diagnostics is degraded image quantification (altered biodistribution and reduced injected activity reaching the target), which matters most for quantitative studies such as dosimetry or lymphoscintigraphy.\n\nExtravasation of a therapeutic radiopharmaceutical is potentially more serious because the higher administered activity and longer-range or higher-LET emissions can cause localised soft-tissue injury, including skin necrosis in severe cases. SNMMI guidance instructs staff to stop the infusion immediately if resistance is felt, swelling appears, or the patient reports pain, and to document the estimated infiltrated volume and site. Symptoms warranting evaluation by a plastic surgeon include swelling greater than 2.5 cm, numbness, blanched or translucent skin, tight or leaking skin, discoloration or bruising, and any circulatory or nerve impairment. Management strategies described in the literature (cooling versus warming, elevation, and rarely surgical excision) are not strongly evidence-based, and EANM/SNMMI procedure guidelines give only limited practical advice, largely confined to the 90Y-ibritumomab tiuxetan (Zevalin) guideline, which recommends local hyperthermia, elevation and gentle massage.\n\nUnder US NRC policy, extravasations have historically been treated as a practice-of-medicine issue rather than a reportable medical event, since they occur even with technically correct injections; however, an extravasation that leads to unintended permanent functional damage can be reportable as a medical event under 10 CFR 35.3045(b), and SNMMI and the NRC's Advisory Committee on the Medical Uses of Isotopes have discussed whether CTCAE grade 3-4 tissue injury from a therapeutic extravasation should trigger notification requirements similar to other medical events.","asOf":"2026-09-22","links":[{"label":"SNMMI: Use of Radiopharmaceuticals guideline (clinical use and administration, extravasation)","url":"https://captions.snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2025/Use%20of%20Radiopharm_FINAL.pdf"},{"label":"van der Pol J, et al. Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review, Eur J Nucl Med Mol Imaging 2017","url":"https://link.springer.com/article/10.1007/s00259-017-3675-7"},{"label":"SNMMI position statement and comments to NRC on extravasation rulemaking, 2023","url":"https://sites.snmmi.org/common/Uploaded%20files/Web/Advocacy%20and%20Initiatives/2023-09-07/NRC%20Comments%20on%20Extravasations%20Rulemaking%209-1-2023.pdf"}],"tags":["injection safety","adverse event","NRC"],"related":["radiopharmaceutical-gmp-release","in-vivo-dosimetry","gamma-probes-dose-calibrators","b-dose-optimisation","f-18","ga-68","tc-99m","i-123","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety","route":"/terms/extravasation-radiopharmaceutical/"}
{"id":"radiation-safety-officer","kind":"term","name":"Radiation Safety Officer (RSO)","aka":[],"tldr":"Every US clinic or hospital that uses radioactive drugs must have one named, specially qualified person responsible for making sure radiation is used and stored safely.","summary":"Under US Nuclear Regulatory Commission rules (10 CFR 35.24), every licensee authorised for the medical use of byproduct material must appoint a Radiation Safety Officer (RSO) in writing, who agrees to be responsible for implementing the facility's radiation protection programme and for ensuring that radiation safety activities follow licensee-approved procedures and regulatory requirements. Management, through the RSO, remains accountable for the programme even though day-to-day duties are delegated.\n\nThe qualification pathway is set out in 10 CFR 35.900 (and its current successor, 35.50 for newer licenses): an individual can qualify either by board certification (for example the American Board of Health Physics, American Board of Radiology, American Board of Nuclear Medicine, or the Board of Pharmaceutical Specialties in Nuclear Pharmacy), or through a structured programme of at least 200 hours of classroom and laboratory training covering radiation physics and instrumentation, radiation protection, mathematics of radioactivity, radiation biology and radiopharmaceutical chemistry, plus one year of full-time supervised experience as a radiation safety technologist, or by already being an authorized user identified on the licensee's own license. A licensee may also appoint one or more Associate Radiation Safety Officers to support the RSO, though the RSO cannot delegate the ultimate authority or responsibility for the programme.\n\nThe RSO role sits alongside, and is distinct from, the Authorized User, who is the physician credentialed to prescribe and administer specific categories of radioactive drugs; a single individual can hold both roles if separately qualified for each. Agreement States (which license the majority of US medical radioactive material users) apply equivalent, NRC-compatible requirements under their own regulations.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.900, Radiation Safety Officer (GovInfo, CFR)","url":"https://www.govinfo.gov/content/pkg/CFR-2004-title10-vol1/pdf/CFR-2004-title10-vol1-sec35-900.pdf"},{"label":"NRC: Authorized Individuals - Radiation Safety Officer and Associate RSO","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/auth-individuals"},{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"}],"tags":["NRC","10 CFR Part 35","radiation protection programme"],"related":["authorized-user","alara","nrc-licensing","hot-lab","radiopharmaceutical-gmp-release"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/radiation-safety-officer/"}
{"id":"authorized-user","kind":"term","name":"Authorized User (AU)","aka":[],"tldr":"In the US, only a physician who has completed specific radiation training and case experience, and who is named on the clinic's license, is legally allowed to order and give radioactive drugs to patients.","summary":"An Authorized User (AU) is a physician, dentist or podiatrist who meets US Nuclear Regulatory Commission training-and-experience requirements under 10 CFR Part 35 and is named as such on a specific medical-use license (or an equivalent permit). Only AUs, and authorized nuclear pharmacists preparing material under their direction, may prescribe or administer byproduct material to patients in the practice of medicine; every administration must follow either an individually written prescription from an AU or a licensee-approved written protocol.\n\nThe requirements differ by category of use. For imaging and localisation studies not requiring a written directive (10 CFR 35.290, covering diagnostic PET and SPECT tracers), a physician needs 700 hours of training and experience including a minimum of 80 hours of classroom and laboratory instruction in radiation physics, protection, mathematics of radioactivity, chemistry of byproduct material and radiation biology, plus supervised work experience covering ordering and receiving radioactive material, dose-calibrator quality control, dosage calculation, and eluting generators. For uses requiring a written directive (10 CFR 35.390, covering therapeutic radiopharmaceuticals such as lutetium-177 or iodine-131 therapy), the bar is higher: 700 hours of training including a minimum of 200 hours of classroom and laboratory work, plus supervised experience administering at least three cases in each dosage category for which authorisation is sought (for example, specific activity thresholds of oral sodium iodide-131). Board certification by a recognised specialty board (such as the American Board of Nuclear Medicine or American Board of Radiology) can substitute for the itemised hour requirements if the certifying board's own process covers the same content and includes an examination.\n\nAn AU already qualified under 35.390 for therapeutic use can add 35.290 diagnostic authorisation with a smaller increment of generator-elution experience, recognising the overlapping physics and safety curriculum. All training and experience must have been obtained within the seven years preceding the license application, or be supported by continuing education and experience since. Individual attestation is provided by a preceptor AU or a residency programme director, and the NRC or Agreement State reviews the credentials before amending the license; the NRC does not issue any credential directly to the individual.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.290, Training for imaging and localization studies (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.290"},{"label":"10 CFR 35.390, Training for use of unsealed byproduct material for which a written directive is required (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.390"},{"label":"NRC: Authorized Individuals - definitions and license amendment process","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/auth-individuals"}],"tags":["NRC","10 CFR Part 35","physician credentialing"],"related":["radiation-safety-officer","nrc-licensing","hot-lab","dose-calibrator","release-criteria","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/authorized-user/"}
{"id":"alara","kind":"term","name":"ALARA (as low as is reasonably achievable)","aka":[],"tldr":"A rule that radiation should always be kept as low as practically possible, not just below the legal limit, taking into account cost, technology and benefit.","summary":"ALARA (as low as is reasonably achievable) is defined in US Nuclear Regulatory Commission regulations (10 CFR 20.1003) as making every reasonable effort to maintain radiation exposures as far below the dose limits in 10 CFR Part 20 as is practical, taking into account the state of technology, the economics of improvements in relation to that technology and to benefits for public health and safety, and other societal and socioeconomic considerations, all in the context of using nuclear energy and licensed materials in the public interest. It is not itself a numeric dose limit; it is an operating principle that sits below the hard limits and requires continual effort to reduce doses further wherever reasonably practical.\n\n10 CFR 20.1101 requires every licensee to develop, document and implement a radiation protection programme that is commensurate with the scope and extent of licensed activities and sufficient to ensure compliance, with ALARA as its guiding principle for both occupational and public exposure. In a nuclear medicine or radiopharmacy setting this translates into concrete practice: shielding (lead or tungsten syringe shields, L-blocks, hot-cell walls), distance (using tongs or automated dispensers rather than close manual handling), time (minimising time spent near unshielded sources), workflow design that keeps the highest-activity work furthest from staff and the public, and engineering controls such as ventilated hoods for volatile radiopharmaceuticals.\n\nALARA is distinct from, but complementary to, the specific dose limits in Part 20 (for example, 100 mrem/year for members of the public, or 2 mrem in any one hour in unrestricted areas) and the training-and-equipment requirements of Part 35 for medical use of byproduct material; a facility can be within all numeric limits and still be found non-compliant if it has not made the reasonable further efforts ALARA demands, particularly during periodic radiation safety programme reviews and inspections.","asOf":"2026-09-22","links":[{"label":"10 CFR 20.1003, Definitions - ALARA (NRC eCFR)","url":"https://www.nrc.gov/reading-rm/doc-collections/cfr/part020/part020-1003.html"},{"label":"eCFR: 10 CFR Part 20, Standards for Protection Against Radiation","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-20"}],"tags":["NRC","radiation protection","10 CFR Part 20"],"related":["radiation-safety-officer","hot-lab","dose-calibrator","authorized-user","gamma-probes-dose-calibrators"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/alara/"}
{"id":"hot-lab","kind":"term","name":"Hot lab (radiopharmacy dispensing area)","aka":[],"tldr":"The specially shielded room in a hospital or radiopharmacy where radioactive drugs are received, checked, prepared and measured before they are given to patients.","summary":"A hot lab is the shielded workspace within a nuclear medicine department or radiopharmacy where unsealed radioactive materials are received, surveyed, assayed, compounded or drawn into unit doses, and staged for use or decay-in-storage disposal. It typically houses a dose calibrator (a shielded re-entrant ionisation chamber used to assay every dose before administration), an L-block workstation with leaded glass shielding, syringe and vial shields of lead or tungsten, a fume hood or laminar-flow cabinet for volatile or aseptic compounding, generator storage (for example Mo-99/Tc-99m generators), a decay-in-storage area for short-lived waste, and contamination survey and monitoring equipment. \"Hot cell\" refers more specifically to a heavily shielded enclosure, often with remote manipulators and lead-glass viewing windows, used to handle the highest-activity materials, such as commercial radiopharmaceutical production or generator processing, without direct manual contact.\n\nBecause the hot lab concentrates the highest activities handled anywhere in a facility, its physical design (shielding thickness, room layout, ventilation and workflow zoning) is calculated by a qualified expert, typically a board-certified medical physicist, based on the isotopes used, weekly workload, occupancy of adjacent areas, and distance to occupied space, with the design goal of keeping public exposure below the 10 CFR 20.1301 limits (2 mrem in any one hour, 100 mrem per year) and occupational exposure within ALARA. Regulatory requirements for the hot lab's instruments and procedures flow from 10 CFR Part 35 (dose calibrators under 35.60/35.63, survey instruments under 35.61, labelling of vials and syringes under 35.69, and daily/weekly area surveys under 35.70).\n\nThe hot lab is where most of the practical burden of radiopharmaceutical GMP and release sits: incoming shipment surveys, generator eluate testing for radionuclidic breakthrough, on-site kit preparation and quality control (radiochemical purity, pH, sterility as applicable under USP <825>), and the final dose-calibrator assay that confirms the activity to be given to each patient matches the prescription.","asOf":"2026-09-22","links":[{"label":"Wikipedia: Hot cell","url":"https://en.wikipedia.org/wiki/Hot_cell"},{"label":"10 CFR Part 35, Subpart C - General Technical Requirements (dose calibrators, surveys, labelling)","url":"https://www.law.cornell.edu/cfr/text/10/part-35/subpart-C"},{"label":"10 CFR 20.1301, Dose limits for individual members of the public (NRC eCFR)","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-20/subpart-D/section-20.1301"}],"tags":["radiopharmacy","shielding","facility design"],"related":["dose-calibrator","radiopharmacy-term","alara","radiation-safety-officer","release-criteria","radionuclide-generators-kits","sterile-fill-finish","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/hot-lab/"}
{"id":"dose-calibrator","kind":"term","name":"Dose calibrator","aka":[],"tldr":"A shielded instrument that measures exactly how much radioactivity is in a syringe or vial before it's given to a patient, so the dose matches the prescription.","summary":"A dose calibrator is a shielded, re-entrant ionisation chamber used to measure the activity (in becquerels or curies) of a radiopharmaceutical dosage before it is administered to a patient. Under US Nuclear Regulatory Commission rules, licensees performing direct dosage measurements must possess and use such instrumentation (10 CFR 35.60, formerly the more prescriptive 35.50), and calibrate it in accordance with nationally recognised standards or the manufacturer's instructions.\n\nUnder the earlier, more detailed version of the rule (still widely followed as practice standard and reflected in NRC guidance such as NUREG-1556 Vol. 9), dose calibrators must be checked for constancy each day of use with a dedicated check source of at least 10 microcuries of radium-226 or 50 microcuries of any other photon-emitting radionuclide; tested for accuracy on installation and at least annually by assaying two sealed sources of different radionuclides, each within 5% of its manufacturer-stated activity; tested for linearity on installation and at least quarterly across the full range of clinical use down to 10 microcuries; and tested for geometry dependence on installation across the range of volumes and containers used clinically. A dose calibrator must be repaired or replaced if its accuracy or constancy error exceeds 10%, and records of every check and test must be retained (historically for three years, per 10 CFR 35.2060).\n\nThe dose calibrator is the instrument that closes the loop between the pharmacy's compounding or dispensing step and the patient: the final patient dose or ordered amount must be radioassayed in it before administration (except for certain unopened manufacturer unit-dose containers), and the measured activity is decay-corrected to the scheduled administration time to confirm it falls within the prescribed and regulatory tolerance. It sits physically in the hot lab alongside survey instruments and syringe/vial shields.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.60"},{"label":"NUREG-1556 Vol. 9: Consolidated Guidance About Materials Licenses (dose calibrator QC criteria)","url":"https://www.nrc.gov/docs/ML0228/ML022830849.pdf"},{"label":"Selected sections of 10 CFR Part 35, historical §35.50 dose calibrator requirements (NCBI Bookshelf)","url":"https://www.ncbi.nlm.nih.gov/books/NBK232708/"}],"tags":["NRC","quality control","instrumentation"],"related":["hot-lab","authorized-user","gamma-probes-dose-calibrators","release-criteria","radiopharmacy-term"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/dose-calibrator/"}
{"id":"radiopharmacy-term","kind":"term","name":"Radiopharmacy (practice and discipline)","aka":[],"tldr":"Radiopharmacy is the specialised branch of pharmacy that prepares radioactive drugs safely, correctly and on time, since these medicines decay and can't simply be reordered from a shelf.","summary":"Radiopharmacy is the pharmacy specialty concerned with the procurement, compounding, quality control, dispensing and record-keeping of radioactive drugs. In the United States its compounding and quality standards are set out in USP General Chapter <825> \"Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging\", which requires that prepared or compounded radiopharmaceuticals meet identity, quality and purity standards from manufacturer labelling, USP monographs or other appropriate sources; that non-sterile compounded components undergo a sterilisation step; that components not certified pyrogen-free undergo bacterial endotoxin testing; and that the final dose or ordered amount be radioassayed in a dose calibrator except for unopened manufacturer containers.\n\nA central radiopharmacy concept is the beyond-use date (BUD): the date and time beyond which a compounded, prepared, repackaged or dispensed radiopharmaceutical must not be administered, determined from the stability of quality attributes such as sterility, radiochemical purity and radionuclidic purity. USP <825> sets reference BUDs of 1 hour for immediate-use sterile radiopharmaceuticals and 99mTc-labelled red blood cells, 6 hours for radiolabelled blood components, 10 hours for direct infusion systems, and 24 hours for radiopharmaceuticals prepared and dispensed under classic sterile compounding conditions. Radionuclidic purity requirements also change with time since calibration: for example, USP monographs for 99mTc radiopharmaceuticals cap the 99Mo radionuclidic impurity at 0.15 microcurie of 99Mo per millicurie of 99Tc-99m at the time of administration, which must be recalculated forward because the ratio increases continuously as the shorter-lived 99mTc decays faster than its 99Mo parent.\n\nDay-to-day radiopharmacy practice includes assaying generator eluate for radionuclidic breakthrough (regulated under 10 CFR 35.204), preparing kits under aseptic technique in the hot lab, performing radiochemical purity testing (commonly thin-layer or paper chromatography) before a preparation is released for patient use, and maintaining records of preparation date and time, activity, component lot numbers, quality-control results and final disposition. The discipline sits at the intersection of pharmacy compounding law, NRC/Agreement State radioactive-materials licensing, and nuclear medicine clinical practice.","asOf":"2026-09-22","links":[{"label":"USP General Chapter <825> Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging (briefing/full text)","url":"https://www.nihs.go.jp/dnfi/pdf/RI_PDF/USP3-1.pdf"},{"label":"USP General Chapter <825> Impact on Nuclear Medicine Technology Practice, J Nucl Med Technol 2020","url":"https://tech.snmjournals.org/content/jnmt/48/2/106.full.pdf"},{"label":"2025 USP <825> Radiopharmaceuticals Addendum","url":"https://content.govdelivery.com/attachments/WADOH/2025/01/25/file_attachments/3142978/2025%20USP%20825%20Radiopharmaceuticals%20Addendum.pdf"}],"tags":["USP <825>","compounding","quality control"],"related":["hot-lab","dose-calibrator","release-criteria","radiopharmacy-network","radiopharmaceutical-gmp-release","sterile-fill-finish","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/radiopharmacy-term/"}
{"id":"release-criteria","kind":"term","name":"Product release criteria (radiopharmaceutical quality control)","aka":[],"tldr":"Before any batch of radioactive drug can be given to a patient, it has to pass a checklist of quality tests, such as being the right radioactive strength, sterile, and chemically pure.","summary":"Product release criteria are the specific quality-control tests and pass/fail limits a radiopharmaceutical must meet before it is dispensed or administered. Under USP General Chapter <825>, licensees preparing or compounding radiopharmaceuticals on site must complete a quality assessment before use, appropriate to the preparation, which can include radionuclidic purity, radiochemical purity, chemical purity, pH, and physical appearance, in addition to sterility and bacterial endotoxin testing for injectable preparations made from non-sterile or non-pyrogen-certified components. Compliance with these tests is not optional: the chapter states that quality testing is mandatory for validating radiochemical purity of the final product through to its beyond-use date, particularly whenever a preparation deviates even slightly from the manufacturer's kit directions.\n\nA representative numeric release criterion is the 99Mo/99mTc radionuclidic purity limit: USP monographs for 99mTc radiopharmaceuticals require that 99Mo not exceed 0.15 microcurie per millicurie of 99Tc-99m at the time of administration, a limit that must be recalculated forward in time because the 99Mo-to-99mTc ratio rises continuously as the shorter-lived daughter decays away faster than the parent. Generator eluates must also be tested for radionuclide \"breakthrough\" of the parent isotope under 10 CFR 35.204, with eluates exceeding the specified limits barred from use and any exceedance reported to the generator manufacturer.\n\nExcept for unopened manufacturer unit-dose containers, the final patient dose or ordered amount must be radioassayed in a dose calibrator immediately before release, with the measured activity mathematically decay-corrected to the scheduled administration (calibration) time; the assayed activity must fall within federal, state, and institutional tolerance limits of the prescribed activity. Radiopharmaceuticals should not be administered if any impurity level exceeds the package insert or USP monograph specification. Records of every preparation, including quality-control results and final disposition, must be retained and are the primary evidence a regulator or accreditor reviews to confirm release criteria were actually met before a dose reached a patient.","asOf":"2026-09-22","links":[{"label":"USP General Chapter <825>, Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging","url":"https://www.pharmacy.la.gov/assets/docs/Staff/USP_825-Radiopharmaceuticals_2020-1201.pdf"},{"label":"USP General Chapter <825> Impact on Nuclear Medicine Technology Practice, J Nucl Med Technol 2020","url":"https://tech.snmjournals.org/content/jnmt/48/2/106.full.pdf"},{"label":"ACR-SPR-SNMMI practice parameter excerpt on assay and administration quality control","url":"https://gravitas.acr.org/PPTS/DownloadPreviewDocument?DocId=171"}],"tags":["USP <825>","quality control","GMP"],"related":["radiopharmacy-term","hot-lab","dose-calibrator","radiopharmaceutical-gmp-release","patient-release-criteria","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/release-criteria/"}
{"id":"nrc-licensing","kind":"term","name":"NRC medical-use licensing (10 CFR Part 35)","aka":[],"tldr":"Any US clinic that wants to use radioactive drugs for patients must first get a specific license, either from the federal Nuclear Regulatory Commission or from the state government where it's located, proving it can handle the material safely.","summary":"In the United States, a person or institution may manufacture, produce, acquire, receive, possess, prepare, use or transfer byproduct material for medical use only under a specific license issued by the Nuclear Regulatory Commission (NRC) or by an Agreement State, under 10 CFR Part 35, \"Medical Use of Byproduct Material.\" Part 35 divides medical use into distinct categories with their own subparts: uptake, dilution and excretion studies not requiring a written directive (35.100); imaging and localisation studies not requiring a written directive, i.e. most diagnostic PET and SPECT tracers (35.200); uses requiring a written directive, i.e. most therapeutic radiopharmaceuticals (35.300); manual brachytherapy (35.400); sealed sources for diagnostic use (35.500); sealed sources in remote afterloaders, teletherapy and gamma stereotactic units (35.600); and any other medical use not specifically addressed elsewhere (35.1000).\n\nAgreement States are US states that have entered into an agreement with the NRC under section 274b of the Atomic Energy Act, giving the state authority to license and inspect byproduct, source, and certain special nuclear materials within its borders; the large majority of US states are Agreement States, so most medical-use licenses are issued and inspected by state radiation control programmes rather than the NRC directly, applying regulations that must be compatible with, though not always textually identical to, Part 35. Non-Agreement States and federal enclaves remain under direct NRC jurisdiction.\n\nThe NRC issues two broad types of specific license for medical use: a specific license of limited scope, tailored to the particular radionuclides, forms and medical uses named on the license, and a specific license of broad scope (issued under 10 CFR Part 33), which authorises a wider range of quantities and uses, typically for large academic medical centres, and carries additional internal radiation safety committee obligations in exchange for more flexibility. An applicant applies using NRC Form 313, must demonstrate through named, individually qualified staff (Authorized Users, Radiation Safety Officer, Authorized Medical Physicists, Authorized Nuclear Pharmacists as applicable) that it is equipped and committed to meet Part 35's safety standards, and must amend its license before adding new radionuclides, new uses, or new addresses of use.","asOf":"2026-09-22","links":[{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material - full text and subpart structure","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"},{"label":"NUREG-1556 Vol. 9: Consolidated Guidance About Materials Licenses for medical use, licensing overview and Agreement States","url":"https://www.nrc.gov/docs/ML1632/ML16328A214.pdf"},{"label":"NRC: Frequently Asked Questions About Licensing Medical Uses of Byproduct Material","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/faqs-part35"}],"tags":["NRC","10 CFR Part 35","Agreement States"],"related":["authorized-user","radiation-safety-officer","hot-lab","alara","patient-release-criteria","dose-calibrator"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/nrc-licensing/"}
{"id":"patient-release-criteria","kind":"term","name":"Patient release criteria after radioactive treatment","aka":[],"tldr":"After certain radioactive treatments, US rules set a specific radiation limit that must be checked before a patient can safely go home, and if the dose to a household member could exceed a lower limit, the patient gets written safety instructions (including, if relevant, guidance on breastfeeding).","summary":"Under 10 CFR 35.75, a US licensee may authorise the release from control of a patient (or a patient carrying an implant) containing unsealed byproduct material or brachytherapy sources if the total effective dose equivalent (TEDE) to any other individual from exposure to the released patient is not likely to exceed 5 mSv (0.5 rem). This single numeric threshold, rather than a fixed activity limit for each radionuclide, is what actually governs same-day release after therapies such as iodine-131 for thyroid cancer, lutetium-177 radioligand therapy, or brachytherapy implants, and licensees typically use NRC-provided tables of activities, dose-rate measurements, or patient-specific calculations to demonstrate compliance before discharge.\n\nA second, lower threshold triggers a documentation and counselling obligation rather than a release bar: if the TEDE to any other individual is likely to exceed 1 mSv (0.1 rem), the released individual (or their parent or guardian) must be given written instructions on actions to keep the dose to others as low as reasonably achievable. If a nursing infant or child could receive more than 1 mSv assuming breastfeeding continues uninterrupted, those instructions must also cover guidance on interrupting or discontinuing breastfeeding and the potential consequences of not following that guidance. The licensee must keep a record of the basis for authorising release and, separately, a record of any instructions given to a breastfeeding patient (10 CFR 35.2075).\n\nThese thresholds are considerably more permissive than the general public dose limit (1 mSv/year total, under 10 CFR Part 20), reflecting a deliberate policy choice that patients undergoing medically necessary radioactive treatment, and the household members who choose to live with them, accept a higher, time-limited exposure than an uninvolved member of the public would. Facilities commonly apply extra margin above the regulatory minimum (for example, discharging only once a fixed dose-rate-at-one-metre threshold is met) and provide take-home instructions covering distance, time and hygiene precautions for a defined number of days, tailored to the isotope's half-life and the specific therapy given. This entry reflects the regulation as published in the eCFR, checked 2026-09-22; consult the current eCFR text for any amendments.","asOf":"2026-09-22","links":[{"label":"eCFR: 10 CFR 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-D/section-35.75"},{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material (subpart structure, 35.2075 recordkeeping)","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"}],"tags":["NRC","10 CFR 35.75","patient discharge"],"related":["nrc-licensing","authorized-user","radiation-safety-officer","radioiodine-therapy","lutathera","pluvicto","alara","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation","route":"/terms/patient-release-criteria/"}
{"id":"theranostic-pair-term","kind":"term","name":"Theranostic pair","aka":[],"tldr":"A matched set of two radioactive drugs built on the exact same molecule: one labelled with a radioactive tag good for taking pictures (a PET scan), the other labelled with a different radioactive tag good for treatment, so the scan predicts where the treatment will go.","summary":"A theranostic pair is a diagnostic and a therapeutic radiopharmaceutical that share the same, or a near-identical, targeting molecule (peptide, small molecule or antibody), so that the biological distribution seen on the diagnostic scan is expected to closely mirror where the therapeutic radiopharmaceutical will localise and deliver radiation dose. The classic and historically first example is 123I/131I sodium iodide, where both agents follow the identical physiological pathway (the sodium-iodide symporter) into the thyroid. The current dominant paradigm labels the same peptide or small-molecule vector with two different chemical elements: a positron emitter for PET imaging (commonly gallium-68, sometimes copper-64 or fluorine-18) and a therapeutic emitter for treatment (commonly lutetium-177 for beta therapy, or actinium-225 for alpha therapy), examples being 68Ga/177Lu-DOTATATE for somatostatin-receptor-positive neuroendocrine tumours and 68Ga/177Lu-PSMA-617 (or PSMA-I&T) for prostate cancer.\n\nBecause the imaging and therapeutic agents in a \"different-element pair\" are chemically distinct compounds rather than isotopes of the same element, their pharmacokinetics can diverge somewhat (different positron/beta energies, different in vivo stability of the chelate, sometimes different affinity), so a positive diagnostic scan is a necessary but not perfect predictor of therapeutic biodistribution; this is one rationale for post-therapy SPECT/CT imaging with the therapeutic radionuclide itself, when it emits an imageable gamma (as 177Lu does), to confirm actual dose delivery. Lutetium-177 is unusual in being \"theranostic on its own\": its beta emission treats while its co-emitted 113/208 keV gamma photons allow SPECT imaging of the same injection, without needing a separate diagnostic radionuclide.\n\nOther reported or developing theranostic pairs include 43/44Sc/47Sc, 64Cu/67Cu, 86Y/90Y, 152Tb/161Tb, 89Zr/177Lu or 225Ac (for CAIX and other antibody-based pairs), and 68Ga/225Ac or 213Bi combinations for alpha therapy planning. The theranostic pair concept underlies the pairing entries in this graph (for example psma-pet-to-rlt and sstr-pet-to-prrt) and is the organising principle behind most modern radioligand development programmes, which typically design a diagnostic and a therapeutic analogue of a new ligand together from the outset.","asOf":"2026-09-22","links":[{"label":"Expanding Theranostic Radiopharmaceuticals for Tumor Diagnosis and Therapy, PMC 2021 (theranostic pair table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8780589/"},{"label":"Molecular theranostics: principles, challenges and controversies, J Med Radiat Sci 2025","url":"https://onlinelibrary.wiley.com/doi/full/10.1002/jmrs.836"},{"label":"Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs, Theranostics 2022","url":"https://www.thno.org/v12p0232.htm"}],"tags":["theranostics","radiochemistry","drug pairing"],"related":["theranostics","psma-pet-to-rlt","sstr-pet-to-prrt","ga68-dotatate","ga68-psma-11","lutathera","pluvicto","f-18","ga-68","i-123","cu-64","zr-89","sc-44","y-86","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"therapy","route":"/terms/theranostic-pair-term/"}
{"id":"flare-phenomenon","kind":"term","name":"Flare phenomenon","aka":[],"tldr":"Right after some cancer treatments start working, a scan can briefly look worse before it looks better, because healing bone or an early immune response makes lesions light up more, not because the cancer has actually grown. Doctors wait and repeat the scan before deciding treatment has failed.","summary":"The flare phenomenon (bone flare or scintigraphic flare) is an apparent early worsening on a bone scan, PET or PSMA-PET scan that reflects a reparative or reactive process rather than true disease progression, and is followed by genuine improvement on later imaging if the underlying treatment is actually working. On technetium-99m bone scintigraphy it appears as new or more intense uptake at existing or previously inconspicuous lesions, driven by reparative osteoblastic mineralisation around healing metastases as bone lesions respond to hormone therapy, chemotherapy or bone-seeking radiopharmaceuticals; it typically appears between two weeks and three months after starting treatment, occasionally as late as six months. Reported incidence varies widely: series in patients starting first-line hormone therapy for metastatic prostate cancer describe flare in roughly 6-41% of patients depending on definition and timing of the repeat scan, and around 10% of patients receiving bone-seeking radiopharmaceutical therapy (strontium-89, samarium-153, rhenium-186, and radium-223) show a comparable flare pattern.\n\nBecause flare can be mistaken for progression, standard practice (reflected in the MD Anderson bone response criteria) is to continue therapy for a minimum of roughly 12 additional weeks before concluding a scan reflects true progression, and to confirm any apparent worsening with a repeat scan 2-3 months later showing subsequent improvement, rather than acting on a single early scan. A parallel phenomenon, PSA flare (a transient early rise in prostate-specific antigen after starting androgen deprivation therapy or antiandrogens, from an initial agonist effect before suppression takes hold), is a distinct biochemical marker that does not always occur together with bone flare; in one series both bone and PSA flare co-occurred in only about one in four patients showing either.\n\nOn PSMA-PET, flare has been studied less consistently: one cohort study found no clear PSMA expression flare after starting androgen-receptor-pathway inhibitors, while retaining the possibility that a short-duration or very early flare could have been missed, so PSMA-PET response assessment guidance generally still recommends confirmatory follow-up imaging before calling early progression, particularly close to treatment initiation.","asOf":"2026-09-22","links":[{"label":"Conteduca V, et al. Flare phenomenon in prostate cancer: recent evidence on new drugs and next generation imaging, Ther Adv Med Oncol 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7907710/"},{"label":"Radiopaedia: Flare phenomenon (bone scintigraphy)","url":"https://radiopaedia.org/articles/flare-phenomenon-bone-scintigraphy?lang=us"},{"label":"Flare phenomenon visualized by 99mTc-bone scintigraphy has favourable prognostic value in mCRPC, Ann Nucl Med 2024","url":"https://link.springer.com/article/10.1007/s12149-024-01914-8"}],"tags":["response assessment","bone imaging","prostate cancer"],"related":["bone-metastases","psa-kinetics","prostate-mcrpc","psma-pet","radium-223","complete-response-term","tc-99m","ra-223","sm-153","sr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging","route":"/terms/flare-phenomenon/"}
{"id":"specific-activity","kind":"term","name":"Specific activity and molar activity","aka":[],"tldr":"A measure of how much of a radioactive drug is genuinely radioactive versus how much is ordinary, non-radioactive filler of the same molecule. Higher specific activity means more radioactive atoms are packed onto the targeting molecules, so fewer 'cold' (non-radioactive) copies compete for the same receptors.","summary":"Specific activity is the activity of a radionuclide divided by the total mass of the element (or the labelled compound) present, expressed in units such as GBq/mg; molar activity is the same idea per mole (GBq/µmol) and is the preferred term when the labelled molecule, not the element, is what matters clinically. Because no radiolabelling reaction is perfectly efficient, every batch of a radiopharmaceutical contains some non-radioactive ('cold') copies of the same targeting molecule alongside the radioactive ones, and specific activity quantifies that ratio.\n\nThe practical stakes are receptor saturation: for a receptor-targeted tracer or therapy (an SSTR or PSMA ligand, for example), the cold carrier competes with the radiolabelled molecule for a limited number of binding sites, so low specific activity can reduce tumour uptake per unit of injected mass. The qualitative terms carrier-free, no-carrier-added (n.c.a.) and carrier-added describe roughly how much stable-isotope carrier is present without stating a number; a 2018 international nomenclature consensus recommends always reporting the measured specific or molar activity rather than relying on these qualitative labels alone.\n\nSpecific activity is determined experimentally, commonly by HPLC (comparing the radioactive peak to a UV mass calibration curve) or, theoretically, from the decay constant and the assumption of no carrier at all. It is a batch-release and formulation parameter tracked in GMP manufacture of PET and therapeutic radiometal agents, and it is specified in clinical trial protocols for tracers such as 18F-fluoromisonidazole or 89Zr-antibody conjugates.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC: determination of specific activity","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf"},{"label":"International consensus nomenclature for radiopharmaceutical chemistry (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5852186/"}],"tags":[],"related":["no-carrier-added","chelator-term","f-18","zr-89"],"indications":[],"sections":[],"technologies":["pet-tracer-manufacturing","radiopharmaceutical-gmp-release","sstr-pet","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/specific-activity/"}
{"id":"no-carrier-added","kind":"term","name":"No-carrier-added (n.c.a.) and carrier-added production","aka":[],"tldr":"A way of describing how 'pure' a batch of radioactive material is: whether ordinary, non-radioactive atoms of the same element were deliberately or accidentally mixed in during manufacture.","summary":"'No-carrier-added' (n.c.a.) describes a radionuclide preparation in which no stable (non-radioactive) isotope of the same element has been intentionally added during manufacture or processing, though trace stable-isotope contamination can still occur incidentally, for example from reagents, the target material or the separation chemistry. 'Carrier-added' means stable isotope was deliberately added, usually to help a separation or purification step proceed. 'Carrier-free' is a stricter, largely theoretical state in which no stable isotope of the element is present at all; it is essentially never achieved or independently proven in practice for radiometals used in radiopharmaceuticals, and most style guides advise against using the term unless analytically verified.\n\nThe distinction matters most for reactor-produced radiometals. Lutetium-177 made by direct neutron irradiation of enriched 176Lu (176Lu(n,γ)177Lu) is carrier-added, because it comes out mixed with a large excess of unreacted, non-radioactive 176Lu in the same chemical form, which cannot be separated from 177Lu by ordinary chemistry since they are the same element. The alternative route, irradiating 176Yb to make 177Yb, which decays to 177Lu, gives no-carrier-added lutetium-177, because ytterbium and lutetium are different elements and can be chemically separated, leaving a batch with much higher specific activity.\n\nThese qualitative labels are convenient shorthand but are not a substitute for a measured specific or molar activity value, which is what a quality-control release specification and a clinical protocol actually need.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC: specific activity determination and no-carrier-added definition","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf"},{"label":"IAEA: cyclotron produced radionuclides, principles and practice","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/trs465_web.pdf"}],"tags":[],"related":["specific-activity","lu-177"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry","route":"/terms/no-carrier-added/"}
{"id":"chelator-term","kind":"term","name":"Chelator (bifunctional chelating agent)","aka":[],"tldr":"A molecular 'cage' that grips a radioactive metal atom tightly so it stays attached to the drug all the way to the tumour, instead of leaking out and going to the wrong part of the body.","summary":"A chelator (or bifunctional chelating agent, BFC/BFCA) is the part of a metal-based radiopharmaceutical that binds the radiometal ion in a stable coordination complex while a second reactive group lets it be covalently attached to a targeting molecule, such as a peptide, antibody or small molecule. The three-part architecture, radiometal plus chelator plus targeting vector (often via a linker), is the standard design of essentially all radiometal radiopharmaceuticals, from diagnostic 68Ga and 64Cu tracers to therapeutic 177Lu, 90Y and 225Ac agents.\n\nDOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is the dominant macrocyclic chelator in the field, used with 68Ga, 111In, 86Y/90Y, 44Sc/47Sc and 177Lu, among others, because its rigid ring gives very high thermodynamic and kinetic stability once the metal is locked in; the trade-off is that labelling usually needs heating (60-95°C for 30-90 minutes), which limits its use with heat-sensitive biomolecules such as intact antibodies. Acyclic chelators (such as DTPA) and other macrocycles (such as NOTA, which forms a stable gallium-68 complex at room temperature) trade some of that ultimate stability for faster, milder labelling conditions.\n\nA poorly matched chelator-metal pair, or incomplete complexation, shows up as radiochemical impurity: unbound or loosely bound radiometal that redistributes in the body (free gallium-68 to bone, free lutetium-177 to bone and liver) rather than following the targeting vector, degrading image quality and increasing off-target dose. Chelator choice is therefore one of the first decisions in designing any new radiometal agent and is documented in the drug's CMC (chemistry, manufacturing and controls) package.","asOf":"2026-09-22","links":[{"label":"Chemical Society Reviews: matching chelators to radiometals for radiopharmaceuticals","url":"https://pubs.rsc.org/en/content/articlehtml/2014/cs/c3cs60304k"},{"label":"PMC: the chemical scaffold of theranostic radiopharmaceuticals","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9143622/"}],"tags":[],"related":["specific-activity","radiochemical-purity","ga-68","in-111","cu-64","sc-44","y-86","lu-177","ac-225","y-90"],"indications":[],"sections":[],"technologies":["site-specific-conjugation","radionuclide-generators-kits","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry","route":"/terms/chelator-term/"}
{"id":"radiochemical-purity","kind":"term","name":"Radiochemical purity (RCP)","aka":[],"tldr":"A quality check on a radioactive drug that asks: of all the radioactivity in the vial, what fraction is actually in the correct, working chemical form, rather than stuck to the wrong molecule or floating free?","summary":"Radiochemical purity is the proportion, usually expressed as a percentage, of the total radioactivity in a radiopharmaceutical preparation that is present in the intended chemical form, that is, correctly bound to the targeting molecule in the right molecular position. It is measured by radio-HPLC or radio-thin-layer chromatography, comparing the area or counts of the desired peak to the total radioactive signal across all peaks, and it is a mandatory batch-release and stability test under pharmacopoeial standards such as the European Pharmacopoeia.\n\nRadiochemical impurities, most often free (unbound) radiometal or radiolysis breakdown products, have a different biodistribution from the intended drug and can degrade image quality in diagnostics or misdirect dose in therapeutics. EANM technical guidance generally asks for RCP above 95% for most diagnostic tracers, though some agents such as 99mTc-HMPAO tolerate lower purity (above 80%) because of their inherent chemistry. For 177Lu-labelled therapeutics, radiochemical purity typically starts near 98% at the end of synthesis and is tracked over the product's shelf-life because it falls with time owing to radiolysis, driven by beta particles from the decaying 177Lu generating reactive free radicals in the aqueous formulation; antioxidant 'radioprotectants' such as ascorbate and gentisic acid are added specifically to slow this decline (see Radiolysis).\n\nRadiochemical purity is distinct from radionuclidic purity, which asks whether the radioactivity comes from the correct radionuclide at all, and from chemical purity, which concerns non-radioactive contaminants.","asOf":"2026-09-22","links":[{"label":"EANM 2019 technologist guide: radiopharmacy, an update","url":"https://eanm.org/wp-content/uploads/2024/06/EANM_2019_TechGuide.pdf"},{"label":"EANM guideline on validation of analytical methods for radiopharmaceuticals (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7016057/"}],"tags":[],"related":["radionuclidic-purity","radiolysis","chelator-term","tc-99m","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","sterile-fill-finish"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry","route":"/terms/radiochemical-purity/"}
{"id":"radionuclidic-purity","kind":"term","name":"Radionuclidic purity","aka":[],"tldr":"A check that the radioactivity in a vial really comes from the intended radioactive element, and not from some other radioactive contaminant left over from how it was made.","summary":"Radionuclidic purity is the proportion of the total radioactivity in a preparation that is due to the stated, intended radionuclide, as opposed to any other radioactive species (radionuclidic impurities) that may have formed alongside it during production. It concerns the identity of the radioactive atoms themselves, not their chemical form (that is radiochemical purity) or the mass of the labelled compound (that is specific activity).\n\nRadionuclidic impurities typically arise from side reactions in the target material during cyclotron or reactor production, or from parent/daughter contamination in a generator system. A well-known example is a technetium-99m generator eluate, where a small amount of the parent molybdenum-99 can break through with the technetium-99m and must be kept below regulatory limits; another is actinium-225 production, where the accompanying actinium-227 impurity level is a live manufacturing and regulatory concern. For fluorine-18 FDG, IAEA guidance specifies acceptance criteria including a measured half-life within 105-115 minutes and no less than 99% of gamma emissions attributable to 18F, verified by gamma-ray spectrometry, which distinguishes radionuclides by the characteristic energies they emit.\n\nRadionuclidic purity is a mandatory release test because an unexpected radionuclide contributes unplanned dose to the patient (with its own, possibly very different, half-life and emission type) and can also corrupt quantitative imaging or dosimetry that assumes a single, known decay scheme.","asOf":"2026-09-22","links":[{"label":"IAEA: radionuclidic identity and purity (educational materials)","url":"https://nucleus.iaea.org/sites/accelerators/Modern%20AKP%20Site%20Assets/Educational%20Materials;%20Radioisotope%20and%20Radiopharmaceutical%20Production%20using%20a%20Medical%20Cyclotron/6-Quality%20Control%20and%20Batch%20Release/Radionuclidic%20Identity%20and%20Purity.pdf"},{"label":"IAEA: cyclotron produced radionuclides, guidance on facility design and production (18F acceptance criteria)","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1515_Web.pdf"}],"tags":[],"related":["radiochemical-purity","specific-activity","f-18","tc-99m","mo-99","ac-225"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","radionuclide-generators-kits","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/radionuclidic-purity/"}
{"id":"becquerel-curie","kind":"term","name":"Becquerel and curie (units of radioactivity)","aka":[],"tldr":"The two units used to state how radioactive something is. The becquerel (the modern, official unit) counts one radioactive decay per second; the curie (the older unit, still common in the United States) equals 37 billion decays per second.","summary":"Activity, the rate at which a radioactive sample decays, is measured in becquerels (Bq), the SI unit, where 1 Bq equals one nuclear disintegration per second. The older, non-SI unit is the curie (Ci), originally based on the activity of one gram of radium-226 and now defined by exact convention as 1 Ci = 3.7 x 10^10 Bq (37 gigabecquerels). The becquerel officially replaced the curie in the International System of Units in 1975, but the curie (and its submultiples, millicurie and microcurie) remains in everyday clinical use in the United States, while most of the rest of the world uses becquerel and its multiples (kBq, MBq, GBq).\n\nBecause radiopharmaceutical doses span many orders of magnitude, from microcurie/kilobecquerel amounts of injected tracer mass to gigabecquerel/multi-hundred-millicurie therapeutic activities, the two unit systems are used side by side in practice: a typical PET tracer dose is quoted as roughly 185-370 MBq (5-10 mCi), while a typical cycle of lutetium-177 radioligand therapy is prescribed as 7.4 GBq (200 mCi). Converting between them uses the fixed factor 1 Ci = 37 GBq, so 1 mCi = 37 MBq and 1 MBq is about 0.027 mCi.\n\nActivity (Bq or Ci) is not the same as absorbed dose (measured in gray) or equivalent/effective dose (measured in sievert): activity describes the source, while gray and sievert describe the energy actually deposited in tissue.","asOf":"2026-09-22","links":[{"label":"BIPM/Wikipedia: becquerel, SI unit of activity","url":"https://en.wikipedia.org/wiki/Becquerel"},{"label":"Wikipedia: curie, definition and conversion to becquerels","url":"https://en.wikipedia.org/wiki/Curie_(unit)"}],"tags":[],"related":["absorbed-dose-term","activity-prescription","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/becquerel-curie/"}
{"id":"absorbed-dose-term","kind":"term","name":"Absorbed dose and the gray (Gy)","aka":[],"tldr":"A measure of how much radiation energy actually landed in a piece of tissue, not how radioactive the source was. It is what determines whether a tumour or an organ is actually being treated or harmed.","summary":"Absorbed dose (symbol D) is the mean energy imparted by ionising radiation to a mass of matter, divided by that mass: D = dε/dm. Its SI unit is the gray (Gy), defined as one joule of absorbed energy per kilogram of tissue (1 Gy = 1 J/kg); the older unit, the rad, equals 0.01 Gy. Absorbed dose is a purely physical quantity, defined for a point, organ, tissue or the whole body, and it applies equally to external-beam radiotherapy and to radiation delivered internally by a radiopharmaceutical.\n\nIn radiopharmaceutical therapy, absorbed dose to tumours and organs at risk (typically kidneys, salivary glands and bone marrow for PSMA and SSTR-targeted agents) is estimated from serial quantitative imaging using the MIRD formalism, and it is the physical quantity that dosimetry-guided treatment tries to optimise: enough gray to the tumour, not too much to the kidneys or marrow. It is distinct from equivalent dose and effective dose (measured in sievert), which apply a biological weighting on top of absorbed dose for radiation protection purposes; for prescribing and evaluating radiopharmaceutical therapy, absorbed dose in gray to the organ or tumour of interest, not sievert, is the clinically relevant quantity.\n\nBecause different radiation types (alpha, beta, gamma) deposit their energy very differently at the microscopic scale even at the same absorbed dose, gray alone does not fully capture biological effect; that is the role of linear energy transfer and relative biological effectiveness.","asOf":"2026-09-22","links":[{"label":"BIPM: Resolution 9 of the 15th CGPM (1975), adoption of the gray","url":"https://www.bipm.org/en/-/resolution-cgpm-15-9"},{"label":"ICRU Report 85a via IAEA/ICTP teaching slides: definition of absorbed dose","url":"https://indico.ictp.it/event/10205/session/2/contribution/4/material/slides/0.pdf"}],"tags":[],"related":["equivalent-dose","mird-formalism","linear-energy-transfer"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/absorbed-dose-term/"}
{"id":"equivalent-dose","kind":"term","name":"Equivalent dose and effective dose (sievert)","aka":[],"tldr":"A way of converting a physical radiation dose into a single number for comparing radiation risk across different types of radiation and different organs. It is used for radiation-protection purposes, not for prescribing cancer treatment doses.","summary":"Equivalent dose (H) adjusts the absorbed dose in an organ or tissue (measured in gray) by a radiation weighting factor (wR) that reflects how biologically damaging a given type of radiation is, compared with photons or beta particles of the same absorbed dose: H_T = sum over R of wR times D_T,R. Current ICRP values are wR = 1 for photons, electrons and beta particles, wR = 2 for protons, and wR = 20 for alpha particles, reflecting alpha particles' much higher biological potency per unit of physical dose. Equivalent dose is expressed in sievert (Sv), the same unit (J/kg) as gray but with a different name to signal that a biological weighting has been applied.\n\nEffective dose (E) goes one step further, multiplying the equivalent dose to each organ by a tissue weighting factor (wT, which sums to 1 across the whole body) that represents that organ's relative contribution to overall cancer and heritable-disease risk from uniform whole-body irradiation, then summing across organs. Effective dose, also in sievert, is the standard quantity used in radiation protection to compare the stochastic (cancer-risk) burden of different exposures, for example a diagnostic PET/CT scan versus natural background radiation.\n\nThese are protection quantities developed by the ICRP for population-level risk management and regulatory dose limits; they are not used to prescribe or evaluate radiopharmaceutical therapy, where the organ-specific absorbed dose in gray (via the MIRD formalism), sometimes adjusted for relative biological effectiveness rather than the fixed regulatory wR, is what guides treatment planning.","asOf":"2026-09-22","links":[{"label":"ICRP: The Use of Dosimetric Quantities in Radiological Protection","url":"https://www.icrp.org/docs/physics_icrp_found_doc_for_web_consult.pdf"},{"label":"ICRPaedia: Absorbed, Equivalent, and Effective Dose","url":"https://icrpaedia.org/Absorbed,_Equivalent,_and_Effective_Dose"}],"tags":[],"related":["absorbed-dose-term","relative-biological-effectiveness"],"indications":[],"sections":[],"technologies":["in-vivo-dosimetry","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/equivalent-dose/"}
{"id":"linear-energy-transfer","kind":"term","name":"Linear energy transfer (LET)","aka":[],"tldr":"A measure of how densely a particle of radiation deposits its energy as it travels through tissue. Alpha particles dump their energy in a short, dense burst; beta particles and gamma rays spread it thinly over a much longer track.","summary":"Linear energy transfer (L or LET) is the average energy that a charged ionising particle transfers to the medium per unit length of its track, L = dE/dl, expressed in keV per micrometre (keV/µm). It describes the spatial density of energy deposition (and therefore of ionisation events) along a particle's path, which is what ultimately determines the biological severity of the damage caused for a given absorbed dose.\n\nRepresentative values illustrate the range: cobalt-60 gamma rays and diagnostic x-rays are low-LET (roughly 0.2-2 keV/µm), beta particles from radionuclides such as lutetium-177 are also low-LET (a 1 MeV beta particle deposits roughly 0.2 keV/µm and travels several millimetres), while alpha particles are high-LET, depositing on the order of 80-150 keV/µm over a track of only tens to about a hundred micrometres (a handful of cell diameters). High-LET radiation causes densely clustered ionisations that produce more complex, harder-to-repair DNA double-strand breaks than the sparse ionisation from low-LET beta or gamma radiation, which is the physical basis for targeted alpha therapy's distinct toxicity and efficacy profile compared with beta-emitting radioligand therapy.\n\nLET is the mechanistic quantity underlying both the regulatory radiation weighting factor used in equivalent dose (wR = 20 for alpha versus 1 for beta/gamma) and the empirically measured relative biological effectiveness used to compare therapeutic effect between alpha- and beta-emitting radiopharmaceuticals.","asOf":"2026-09-22","links":[{"label":"NRC training materials: interaction of charged particles with matter, LET and stopping power","url":"https://www.nrc.gov/docs/ml1122/ml11229a666.pdf"},{"label":"ScienceDirect Topics: linear energy transfer, representative values","url":"https://www.sciencedirect.com/topics/immunology-and-microbiology/linear-energy-transfer"}],"tags":[],"related":["relative-biological-effectiveness","equivalent-dose","alpha-vs-beta","lu-177"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy","auger-electron-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/linear-energy-transfer/"}
{"id":"relative-biological-effectiveness","kind":"term","name":"Relative biological effectiveness (RBE)","aka":[],"tldr":"A number that says how much more (or less) biological damage a given amount of one type of radiation causes compared with the same physical amount of a reference radiation. Alpha particles are typically several times more damaging, gray for gray, than the beta particles used in more established radioligand therapies.","summary":"Relative biological effectiveness (RBE) is defined as the ratio of the absorbed dose of a reference radiation (conventionally x-rays, gamma rays, or a beta emitter) to the absorbed dose of a test radiation required to produce an identical biological effect under otherwise identical conditions: RBE = D(reference)/D(test) for the same endpoint. Unlike the fixed, consensus-based radiation weighting factor (wR) used in the regulatory quantity equivalent dose, RBE is an empirically measured quantity that varies with the specific biological endpoint studied (cell survival, organ toxicity, tumour control), the dose and dose rate, the cell type, and oxygen tension, so a single RBE value cannot be assumed to apply across all contexts.\n\nFor targeted alpha therapy, RBE values for cell-kill endpoints are commonly reported in the range of roughly 3 to 8 relative to external-beam or beta reference radiation, though for stochastic cancer-induction endpoints regulatory bodies use a flat wR of 20 for alpha particles, illustrating why RBE and wR are not interchangeable. In actinium-225 versus lutetium-177 dosimetry specifically, experimental work using DNA double-strand-break markers has reported RBE values around 5, and this figure has been used as a practical multiplier to convert measured absorbed dose in gray into an RBE-weighted dose estimate when comparing alpha and beta radioligand therapies or predicting organ toxicity.\n\nRBE is central to interpreting and comparing dosimetry across the beta-to-alpha pairing strategy in radioligand therapy (for example, sequencing lutetium-177 PSMA therapy with actinium-225 PSMA therapy), because a modest gray value from an alpha emitter can correspond to a much larger biologically effective dose than the same gray value from a beta emitter.","asOf":"2026-09-22","links":[{"label":"PMC: redefining relative biological effectiveness in the context of alpha-particle therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3984880/"},{"label":"PMC: estimation of relative biological effectiveness of 225Ac compared to 177Lu","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10495309/"}],"tags":[],"related":["linear-energy-transfer","equivalent-dose","alpha-vs-beta","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/relative-biological-effectiveness/"}
{"id":"mird-formalism","kind":"term","name":"MIRD formalism","aka":[],"tldr":"The standard recipe physicists use to work out how much radiation dose a patient's organs and tumours actually received from an injected radioactive drug, based on how long it stayed in the body and where it went.","summary":"The Medical Internal Radiation Dose (MIRD) formalism, developed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging, is the standard framework for calculating the absorbed dose to a target region of the body from a radionuclide distributed in one or more source regions. In its simplified organ-level form, the mean absorbed dose to a target region equals the time-integrated activity in a source region multiplied by an 'S value': D = A-tilde x S, where the S value (units of Gy per Bq-s, or a convenient multiple) is a radionuclide- and geometry-specific constant representing the absorbed dose rate per unit activity, computed from the energies and yields of all emitted radiations and the fraction of that energy absorbed in the target given the source-target anatomy (the absorbed fraction).\n\nThe other half of the calculation is the time-integrated activity (historically called cumulated activity), obtained by integrating the time-activity curve, the measured activity in a source region plotted against time after injection, over the treatment or imaging period; dividing by the administered activity gives the time-integrated activity coefficient (formerly 'residence time'). S values have been tabulated for many radionuclides and source-target organ pairs using standardised anthropomorphic reference phantoms (MIRD Pamphlets 11 and 21, and successor tools such as MIRDcalc), and voxel-level S values extend the same schema to patient-specific 3D dosimetry from SPECT/CT or PET/CT.\n\nThe MIRD schema underpins essentially all clinical and research dosimetry for radioligand therapy, including personalised activity prescription, and it is functionally similar to (and cross-validated against) the ICRP's own internal dosimetry system, both built on the same underlying physics of time-integrated activity and absorbed fraction.","asOf":"2026-09-22","links":[{"label":"Journal of Nuclear Medicine: MIRD Pamphlet No. 21, a generalized schema for radiopharmaceutical dosimetry","url":"https://jnm.snmjournals.org/content/50/3/477"},{"label":"Journal of Nuclear Medicine Technology: the MIRD schema for radiopharmaceutical dosimetry, a review","url":"https://tech.snmjournals.org/content/jnmt/52/2/74.full.pdf"}],"tags":[],"related":["absorbed-dose-term","time-activity-curve","activity-prescription"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/mird-formalism/"}
{"id":"time-activity-curve","kind":"term","name":"Time-activity curve (TAC)","aka":[],"tldr":"A graph of how much of an injected radioactive drug is present in an organ or tumour at different times after the injection. It shows the drug arriving, peaking and then clearing out, and it is the raw data that personalised radiation-dose calculations are built from.","summary":"A time-activity curve (TAC) plots measured radioactivity (or activity concentration) in a region of interest, an organ, a tumour, blood, or the whole body, against time after a radiopharmaceutical is administered. It is generated from a series of quantitative images (dynamic PET frames, or sequential SPECT/CT or planar scans taken at several time points after a therapeutic injection) or from direct sampling such as blood or excreta counting.\n\nThe shape of the TAC reflects both the physical decay of the radionuclide and the biological uptake, retention and clearance of the labelled compound in that tissue; separating these two contributions is why dosimetry needs the effective half-life rather than the physical half-life alone. Integrating the area under a TAC over the intended dose-integration period gives the time-integrated activity (historically 'cumulated activity'), and dividing that by the administered activity gives the time-integrated activity coefficient, the direct input to the MIRD dose equation. Because TAC shape is usually inferred from only a handful of imaging time points (commonly three to four samples spanning a few hours to about a week after 177Lu therapy) and then fitted with an exponential or other analytical function, the number, timing and spacing of these samples, and the choice of fitting model, are recognised as major, site-dependent sources of variability in radioligand-therapy dosimetry.\n\nAccurate TAC measurement matters clinically because both under- and over-sampling can bias the estimated absorbed dose to kidneys, marrow or tumour, which in turn affects dosimetry-guided activity prescription and estimates of nephrotoxicity or haematotoxicity risk.","asOf":"2026-09-22","links":[{"label":"PMC: understanding time-activity curve and time-integrated activity coefficient calculation in radiopharmaceutical therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12464796/"},{"label":"EANM guidance document: dosimetry for first-in-human studies","url":"https://link.springer.com/content/pdf/10.1007/s00259-024-06640-x.pdf"}],"tags":[],"related":["mird-formalism","decay-correction","effective-half-life","activity-prescription","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/time-activity-curve/"}
{"id":"biological-half-life","kind":"term","name":"Biological half-life","aka":[],"tldr":"The time it takes the body to clear out half of a substance through ordinary biological processes (metabolism and excretion), separate from any radioactive decay. A drug that the kidneys clear quickly has a short biological half-life regardless of which radioactive atom is attached to it.","summary":"Biological half-life is the time required for the amount of a substance present in an organ or the whole body to fall to half its original value through biological elimination processes alone, that is, metabolic breakdown, renal or hepatobiliary excretion, or other clearance mechanisms, independent of any radioactive decay of an attached isotope. It is a pharmacokinetic property of the molecule (and of the specific tissue considered), not of the radionuclide, and it is influenced by physiological factors such as renal function, hydration and hepatic clearance.\n\nBiological half-life is measured directly from a decay-corrected time-activity curve, or inferred from the biodistribution of a stable-isotope-labelled or otherwise trackable analogue of the compound. In radiopharmaceutical dosimetry it is combined with the physical (radioactive) half-life to give the effective half-life, which is the quantity that actually determines how quickly the radioactivity, and therefore the absorbed dose rate, declines in a given organ or tumour after administration.\n\nBecause biological half-life is independent of the isotope used, the same targeting molecule with different attached radionuclides (a diagnostic and a therapeutic pair) is expected to share very similar tissue biological half-lives, an assumption that underlies using a diagnostic imaging agent's kinetics (for example gallium-68 or copper-64 labelled) to predict dosimetry for its therapeutic counterpart (lutetium-177 or actinium-225 labelled) in theranostic pairs.","asOf":"2026-09-22","links":[{"label":"Radiopharmacy teaching notes (Loyola University Chicago): effective half-life","url":"https://www.lumen.luc.edu/lumen/meded/radio/nuc_med/radpharm/sect-a3.htm"},{"label":"DOE-HDBK-1122-99: radiological control technician training, biological half-life","url":"https://www.energy.gov/sites/prod/files/2013/07/f2/hdbk-1122-04_sg112_0.pdf"}],"tags":[],"related":["effective-half-life","half-life","time-activity-curve","ga-68","cu-64","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/biological-half-life/"}
{"id":"effective-half-life","kind":"term","name":"Effective half-life","aka":[],"tldr":"The real-world time it takes for the radioactivity in a patient's organ to fall by half, combining both the radioactive atom's own decay and the body's own clearance of the drug. It is always shorter than either process acting alone, and it is the number that actually drives how much radiation dose an organ receives.","summary":"The effective half-life (Teff) is the time required for the radioactivity of a radiopharmaceutical within an organ or the whole body to fall to half its original value under the combined action of radioactive decay (physical half-life, Tphys) and biological elimination (biological half-life, Tbiol). Because both processes remove activity in parallel and independently, their rate constants add: 1/Teff = 1/Tphys + 1/Tbiol, equivalently Teff = (Tphys x Tbiol)/(Tphys + Tbiol); Teff is always shorter than whichever of Tphys or Tbiol is shorter, and it converges towards the shorter of the two when the two half-lives differ greatly (for a radionuclide with a very long physical half-life and fast biological clearance, Teff approaches Tbiol, and vice versa).\n\nEffective half-life is the quantity that actually appears in dosimetry calculations, because it describes how the true, measurable radioactivity in a source organ declines over time, which is exactly what a time-activity curve records and what must be integrated to obtain the time-integrated activity used in the MIRD formalism. It can be measured directly from serial quantitative imaging without needing to separately determine the physical and biological components.\n\nA practical example: 177Lu has a physical half-life of about 6.65 days; if a PSMA-targeted ligand clears from the kidneys with a biological half-life of a few days, the effective half-life in the kidney will be shorter than 6.65 days, meaning the kidney's radiation exposure is delivered, and finishes, faster than lutetium-177's own decay alone would suggest.","asOf":"2026-09-22","links":[{"label":"Wikipedia: effective half-life, derivation and formula","url":"https://en.wikipedia.org/wiki/Effective_half-life"},{"label":"Radiopharmacy teaching notes (Loyola University Chicago): effective, biological and physical half-life","url":"https://www.lumen.luc.edu/lumen/meded/radio/nuc_med/radpharm/sect-a3.htm"}],"tags":[],"related":["biological-half-life","half-life","time-activity-curve","decay-correction","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/effective-half-life/"}
{"id":"radiolysis","kind":"term","name":"Radiolysis (self-radiolysis of radiopharmaceuticals)","aka":[],"tldr":"A radioactive drug can damage itself: the radiation it gives off breaks apart water and other molecules in the vial, creating reactive fragments that attack the drug molecule and reduce how much of it is still working correctly by the time it reaches the patient.","summary":"Radiolysis is the chemical decomposition of a radiopharmaceutical caused by its own emitted radiation, primarily through the radiolysis of water in the formulation, which generates highly reactive free radicals (such as hydroxyl radicals) that go on to damage the targeting molecule or its chelator. It is distinct from radioactive decay of the radionuclide itself; radiolysis affects the chemical integrity of the drug molecule the radionuclide is attached to, and it is measured as a fall in radiochemical purity over time.\n\nRadiolysis is a particularly significant problem for high-activity, high-specific-activity therapeutic radiometal preparations such as 177Lu-labelled PSMA and somatostatin-receptor ligands, because beta particles emitted by 177Lu interact with the surrounding water to produce radicals that attack the peptide or chelator. Published data show 177Lu-PSMA-617 radiochemical purity falling from about 98% to roughly 80% within 24 hours at room temperature without adequate protection, and falling to single-digit percentages within 24 hours with no radioprotectant at all, whereas with adequate antioxidant protection and cold storage it can be kept above 95% for 48 hours or longer.\n\nRadiolysis is controlled in manufacturing and formulation by adding radioprotectant ('quencher') compounds, most commonly ascorbic acid/sodium ascorbate, often combined with gentisic acid or methionine, which scavenge the reactive radicals before they reach the drug molecule; by keeping the radioactive concentration below a set threshold (diluting the product); and by storing and transporting the finished product refrigerated or frozen. The FDA labels for Lutathera (177Lu-dotatate) and Pluvicto (177Lu-vipivotide tetraxetan) specify their gentisic acid and ascorbate/sodium ascorbate content and corresponding shelf-lives (78 hours and 120 hours respectively) as part of managing radiolysis.","asOf":"2026-09-22","links":[{"label":"PMC: radiolysis-associated decrease in radiochemical purity of 177Lu-radiopharmaceuticals and comparison of quenchers","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9967390/"},{"label":"Bioconjugate Chemistry: ascorbic acid as a buffer agent and radiolytic stabilizer for metalloradiopharmaceuticals","url":"https://pubs.acs.org/doi/10.1021/bc034109i"}],"tags":[],"related":["radiochemical-purity","chelator-term","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","sterile-fill-finish","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry","route":"/terms/radiolysis/"}
{"id":"decay-correction","kind":"term","name":"Decay correction","aka":[],"tldr":"Adjusting a radioactivity measurement to account for the fact that the sample kept decaying between the moment it was measured and the moment you actually care about, such as when the dose was drawn up versus when it was injected, or between two scans taken hours apart.","summary":"Decay correction is the mathematical adjustment of a measured activity or image intensity to remove the effect of ongoing radioactive decay between the time of measurement and a chosen reference time, using the standard exponential decay law At = A0 x e^(-λt), where λ = ln(2)/T-half is the decay constant and t is the elapsed time. Without this correction, any comparison of activity across two different times, whether it is checking the activity in a dose calibrator against the time of patient injection, or comparing two frames of a dynamic PET scan, or comparing organ uptake on serial post-therapy SPECT images taken days apart, would confound genuine biological change with the trivial fact that the radionuclide has simply decayed further by the later time point.\n\nIn practice, decay correction is applied both to individual imaging frames (each PET or SPECT frame is corrected back to a common reference time, commonly either the frame start time, its mid-point, or the injection time) and to any activity measurement recorded away from the time it is needed, such as calculating the percentage of injected activity present in an organ, which requires decay-correcting the measured organ activity back to, or the injected activity forward to, a common time point. For dynamic and quantitative studies, the correction must also account for decay occurring during the frame acquisition itself, not just between frames, particularly for short-half-life radionuclides such as rubidium-82 or oxygen-15 relative to the scan duration.\n\nGetting the decay-correction convention wrong, or applying it inconsistently between the dose calibrator, the scanner and the dosimetry software, is a recognised, easily overlooked source of quantitative error in both diagnostic quantification (SUV, kinetic modelling) and therapeutic dosimetry.","asOf":"2026-09-22","links":[{"label":"IAEA Human Health Reports No. 9: quantitative nuclear medicine imaging, decay correction","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1605_web.pdf"},{"label":"Journal of Nuclear Medicine Technology: decay correction for quantitative myocardial PET perfusion","url":"https://tech.snmjournals.org/content/jnmt/early/2021/09/27/jnmt.121.262320.full.pdf"}],"tags":[],"related":["time-activity-curve","effective-half-life","becquerel-curie","o-15","rb-82"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","pet","spect"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/decay-correction/"}
{"id":"partial-volume-effect","kind":"term","name":"Partial volume effect (PVE)","aka":[],"tldr":"A PET or SPECT scan can make small tumours or lesions look fainter than they really are, simply because the scanner cannot see fine detail perfectly; the true 'brightness' gets smeared out over a wider area, especially in objects smaller than about 1-2 cm.","summary":"The partial volume effect is the systematic underestimation of measured activity concentration in objects that are small relative to the spatial resolution of a PET or SPECT imaging system, caused by two combined phenomena: the finite spatial resolution of the scanner blurs the true activity distribution (a 3D convolution with the system's point-spread function), causing signal to 'spill out' of small hot lesions and background signal to 'spill in'; and the sampling of a continuous activity distribution onto a discrete voxel grid means boundary voxels contain a mixture of tissues (the tissue-fraction effect). Both effects become significant when an object's smallest dimension is below roughly two to three times the system's full-width-at-half-maximum (FWHM) spatial resolution, corresponding to roughly 6-15 mm for typical PET systems and roughly 14-25 mm for SPECT systems, which have poorer intrinsic resolution.\n\nThe practical consequence is a size-dependent, reproducible bias, not random noise: the smaller the lesion, the greater the underestimation of measured uptake (SUVmax or SUVmean) or, for post-therapy dosimetry, of the true absorbed dose. In one worked clinical example, SPECT-based lesion dosimetry for 177Lu therapy underestimated the true absorbed dose by more than 60% in a roughly 1 cm lesion and by more than 99% in a lesion only a few millimetres across.\n\nPartial volume effect matters for radiopharmaceutical therapy dosimetry because small metastases, exactly the lesions most likely to be missed or under-dosed, are the ones most affected; it also affects diagnostic PET quantification, where small lymph nodes below about 10 mm read out with substantially lower SUV than their true uptake. Partial volume correction methods (recovery-coefficient-based, MRI- or CT-guided) can partly compensate but rarely restore full accuracy for sub-centimetre structures, and current guidance recommends excluding lesions below about 10 mm from quantitative analysis unless a validated correction method is applied.","asOf":"2026-09-22","links":[{"label":"PMC: partial volume effect in SPECT and PET imaging and impact on dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9803618/"},{"label":"Journal of Nuclear Medicine: partial-volume effect in PET tumor imaging","url":"https://jnm.snmjournals.org/content/48/6/932"}],"tags":[],"related":["attenuation-correction","suv","time-of-flight-pet","lu-177"],"indications":[],"sections":[],"technologies":["pet","spect","quantitative-imaging-biomarkers","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/partial-volume-effect/"}
{"id":"attenuation-correction","kind":"term","name":"Attenuation correction","aka":[],"tldr":"Radiation coming from deep inside the body has to pass through more tissue to reach the scanner's detectors than radiation from near the skin, so without correction, deep organs look falsely dim. Attenuation correction uses a separate scan (usually a CT) to fix this and make the image quantitatively accurate.","summary":"Attenuation is the loss of PET or SPECT signal that occurs when photons emitted inside the body are absorbed or scattered before they escape and reach the detector; because photons emitted deep in the body must traverse more tissue than those emitted near the surface, uncorrected images make deep structures appear falsely cold and superficial tissue falsely hot. Attenuation correction is the processing step that compensates for this, turning PET or SPECT from a qualitative picture into a quantitatively meaningful measurement of activity concentration, the basis for standardised uptake value (SUV) and for dosimetry calculations.\n\nIn PET, an annihilation event produces two 511 keV photons travelling in opposite directions; because attenuation depends on the total tissue thickness traversed by both photons along their combined path (the line of response), the attenuation correction factor for that path can be computed independent of exactly where along the path the decay occurred, making PET attenuation correction mathematically straightforward once the tissue attenuation map is known. In modern PET/CT and SPECT/CT, this attenuation map is derived from the CT scan: the CT's x-ray attenuation values (measured at a low, polyenergetic effective energy around 70 keV) must be mathematically rescaled to the much higher, monoenergetic energy of the emission photons (511 keV for PET, the specific gamma energy for a given SPECT radionuclide, such as 208 keV for 177Lu) before being applied as a correction, since attenuation is strongly energy-dependent.\n\nAttenuation correction is one of the largest and most consequential physical corrections applied to PET and SPECT data, essential for accurate SUV measurement, lesion detectability, and any dosimetry that depends on absolute activity quantification; historically it was performed with a rotating external radioactive transmission source before CT-based methods became standard.","asOf":"2026-09-22","links":[{"label":"AAPM (Kinahan): CT-based attenuation correction (CTAC), artifacts, and quantitation in PET/CT","url":"https://www.aapm.org/meetings/08ss/documents/Kinahan.pdf"},{"label":"PMC: attenuation correction in emission tomography using synergistic PET/MR data","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4715007/"}],"tags":[],"related":["partial-volume-effect","suv","time-of-flight-pet","lu-177"],"indications":[],"sections":[],"technologies":["pet-ct","spect-ct","pet","spect","quantitative-imaging-biomarkers"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/attenuation-correction/"}
{"id":"time-of-flight-pet","kind":"term","name":"Time-of-flight (TOF) PET","aka":[],"tldr":"A more precise kind of PET scanner that measures the tiny difference in arrival time between the two flashes of light produced by each radioactive decay, which helps pinpoint where in the body the decay happened and produces clearer, less noisy images, especially in larger patients.","summary":"In PET, a positron annihilates with an electron to produce two 511 keV photons travelling in almost exactly opposite directions; the scanner detects both photons in coincidence and knows the decay occurred somewhere along the line connecting the two detectors (the line of response), but conventional PET has no information about where along that line. Time-of-flight (TOF) PET measures the small difference in the two photons' arrival times with high-precision timing electronics and fast scintillator crystals, which localises the annihilation point to a smaller segment of the line of response: the positional uncertainty is Δx = c x Δt / 2, where c is the speed of light and Δt is the scanner's coincidence timing resolution.\n\nModern clinical TOF-PET scanners achieve coincidence timing resolutions in the range of roughly 200-400 picoseconds, corresponding to a spatial localisation of roughly 3-6 cm along the line of response; this does not by itself improve the intrinsic spatial resolution of the image (still around 4-5 mm, set by detector and reconstruction factors), but it substantially reduces statistical noise during image reconstruction because each detected event only needs to be redistributed across a much shorter segment of possible locations rather than the full line of response. The resulting gain in image signal-to-noise ratio is proportional to the square root of the object size (patient girth) divided by the timing resolution, so the benefit of TOF is greatest in larger patients.\n\nClinically, TOF capability improves lesion detectability, allows shorter scan times or lower injected activity for the same image quality, and is now standard on modern PET/CT and total-body PET systems used for oncological imaging, including PSMA, SSTR and FDG PET.","asOf":"2026-09-22","links":[{"label":"PMC: update on time-of-flight PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4287223/"},{"label":"PMC: advances in time-of-flight PET","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4747834/"}],"tags":[],"related":["attenuation-correction","partial-volume-effect"],"indications":[],"sections":[],"technologies":["pet","pet-ct","nuclear-medicine-hardware","total-body-pet-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics","route":"/terms/time-of-flight-pet/"}
{"id":"activity-prescription","kind":"term","name":"Activity prescription: fixed versus dosimetry-guided dosing","aka":[],"tldr":"Deciding how much radioactive drug to give a patient. Most approved radioligand therapies today use the same fixed amount for everyone, but some clinics instead measure each patient's own radiation exposure and adjust the amount up or down to try to give more benefit with less harm.","summary":"Activity prescription is the process of deciding how much radioactivity (in gigabecquerel or millicurie) to administer per cycle of a radiopharmaceutical therapy, and how many cycles to give. Two broad approaches are used. Fixed (empirical) activity prescription gives every eligible patient the same standard activity per cycle, as established in the pivotal trials: 177Lu-PSMA-617 (Pluvicto) is approved and administered as 7.4 GBq (200 mCi) every six weeks for up to six cycles, as tested in the VISION trial, and 177Lu-dotatate (Lutathera) as a fixed 7.4 GBq per cycle for four cycles, as tested in NETTER-1, with dose reductions on toxicity but no upward personalisation. Regulators have approved these regimens without requiring patient-specific dosimetry for in-label use.\n\nDosimetry-guided (personalised) activity prescription instead measures each patient's own absorbed dose to organs at risk (chiefly kidneys and, for PSMA agents, salivary glands, and bone marrow for both) from an early cycle, using serial quantitative imaging and the MIRD formalism, and then adjusts subsequent cycle activity, or the number of cycles, to approach an organ dose-tolerance threshold (commonly cited working limits are around 23 Gy cumulative to the kidneys and around 2 Gy to red marrow) rather than stopping at a fixed number of fixed-size doses. Reported mean absorbed doses per unit administered activity vary widely between patients (for example roughly 0.4-1.9 Gy/GBq to salivary glands and roughly 0.4-1.0 Gy/GBq to kidneys for 177Lu-PSMA agents), which is the empirical basis for the argument that a single fixed activity under- or over-treats a substantial fraction of patients.\n\nDosimetry-guided prescription is used selectively in academic centres and in some national protocols, and is an active area of clinical trial development (see the idea of dosimetry-personalised PRRT instead of four fixed cycles), but it is more resource-intensive, requiring multiple post-therapy scans, quantitative calibration and physicist time, and has not replaced fixed dosing as the regulatory standard for the approved indications.","asOf":"2026-09-22","links":[{"label":"PMC: joint EANM/SNMMI procedure guideline for 177Lu-labelled PSMA radioligand therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"},{"label":"PMC: dosimetry in radiopharmaceutical therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12079709/"}],"tags":[],"related":["mird-formalism","time-activity-curve","becquerel-curie","lu-177"],"indications":[],"sections":[],"technologies":["lu177-radioligand-therapy","prrt","radioligand-dosimetry","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry","route":"/terms/activity-prescription/"}
{"id":"zircon","kind":"trial","name":"ZIRCON","aka":["89Zr-girentuximab phase 3 trial"],"tldr":"A single PET scan with a radioactive antibody (89Zr-girentuximab, brand TLX250-CDx) can tell whether an unexplained kidney lump is a clear cell kidney cancer before surgery, so some patients might be spared an unnecessary biopsy or operation.","summary":"ZIRCON was a prospective, open-label, multicentre phase 3 trial across 36 sites in nine countries that evaluated [89Zr]Zr-girentuximab PET-CT, a radiolabelled monoclonal antibody targeting carbonic anhydrase IX (CAIX), in patients with an indeterminate renal mass (cT1, up to 7 cm) scheduled for nephrectomy. Patients received a single dose (37 MBq, 10 mg girentuximab) five days before abdominal PET-CT, and blinded central histopathology from the resected specimen served as the reference standard.\n\nOf 371 patients screened, 300 received the tracer and 284 were evaluable for the primary analysis. Mean sensitivity was 85.5% and mean specificity was 87.0%, both exceeding the prespecified thresholds for all three independent readers; performance was maintained in the cT1a (up to 4 cm) subgroup. Safety was favourable, with most adverse events attributable to the subsequent surgery rather than the tracer.\n\nThe result supports use of CAIX PET as a non-invasive complement to cross-sectional imaging for risk-stratifying small renal masses, potentially reducing biopsies and overtreatment of benign lesions. TLX250-CDx has not yet received FDA or EMA marketing approval as of this record's date; ZIRCON is the pivotal trial underpinning that filing.","status":"completed","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2024: ZIRCON primary results (Shuch et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"ClinicalTrials.gov: NCT03849118","url":"https://clinicaltrials.gov/study/NCT03849118"}],"tags":["diagnostic trial","renal cell carcinoma","immuno-PET"],"related":["girentuximab-zr89","caix-pet","rcc","telix","zr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03849118","phase":"3","setting":"Adults with a single indeterminate renal mass (cT1, up to 7 cm) suspicious for clear cell renal cell carcinoma, scheduled for nephrectomy; a diagnostic (imaging) trial, not a treatment line","sponsor":"Telix Pharmaceuticals","result":"Met both co-primary endpoints: mean sensitivity 85.5% (95% CI 81.5-89.6) and mean specificity 87.0% (95% CI 81.0-93.1) for detecting clear cell renal cell carcinoma by 89Zr-girentuximab PET-CT against blinded central histopathology (Shuch et al., Lancet Oncology 2024)","yearReported":2024,"enrolled":300,"enrolledBasis":"registry","outcomes":[{"endpoint":"Sensitivity for ccRCC detection vs surgical histopathology","primary":true,"unit":"%","arms":[{"name":"89Zr-girentuximab PET-CT","n":284,"value":85.5,"note":"95% CI 81.5-89.6, mean of 3 independent readers"}],"source":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"endpoint":"Specificity for ccRCC detection vs surgical histopathology","primary":true,"unit":"%","arms":[{"name":"89Zr-girentuximab PET-CT","n":284,"value":87,"note":"95% CI 81.0-93.1, mean of 3 independent readers"}],"source":"https://pubmed.ncbi.nlm.nih.gov/39270701/"}],"route":"/trials/zircon/"}
{"id":"lighthouse","kind":"trial","name":"LIGHTHOUSE","aka":["18F-rhPSMA-7.3 newly diagnosed prostate cancer trial"],"tldr":"A PET scan using a PSMA-targeting tracer (later approved as Posluma) was tested in men newly diagnosed with high-risk prostate cancer to see how well it spots cancer that has already spread to lymph nodes or elsewhere in the body before surgery.","summary":"LIGHTHOUSE was a phase 3, prospective, multicentre, single-arm imaging trial of 18F-rhPSMA-7.3 (later named flotufolastat F-18, brand Posluma) in men with newly diagnosed unfavourable intermediate- to very-high-risk prostate cancer planned for radical prostatectomy with pelvic lymph node dissection. The co-primary endpoints were patient-level sensitivity and specificity for pelvic lymph node metastases, using histopathology at lymphadenectomy as the reference standard, evaluated by three blinded independent readers.\n\nOf 356 enrolled patients, 296 formed the efficacy analysis population. Specificity was high (93-97%) and met the pre-specified threshold for all readers, but sensitivity (23-30%) fell short of the statistical bar, consistent with the modest nodal sensitivity typical of PSMA PET tracers as a class. A separate analysis of extrapelvic (M1) findings, reported at ASCO GU 2023, found a verified detection rate of 10-15% among 335 men, concentrated in bone. No serious adverse events were observed.\n\nLIGHTHOUSE, alongside the companion SPOTLIGHT trial in biochemical recurrence, formed the basis of the FDA approval of flotufolastat F-18 (Posluma) for PSMA PET imaging in both newly diagnosed unfavourable-risk and recurrent prostate cancer.","status":"completed","asOf":"2026-09-22","links":[{"label":"European Urology 2023: LIGHTHOUSE primary results","url":"https://pubmed.ncbi.nlm.nih.gov/37414702/"},{"label":"ClinicalTrials.gov: NCT04186819","url":"https://clinicaltrials.gov/study/NCT04186819"},{"label":"Blue Earth Diagnostics: LIGHTHOUSE topline results announcement","url":"https://www.itnonline.com/content/blue-earth-diagnostics-announces-efficacy-and-safety-results-phase-3-lighthouse-trial"}],"tags":["diagnostic trial","prostate cancer","staging"],"related":["flotufolastat","psma-pet","prostate-high-risk","blue-earth-diagnostics","spotlight","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04186819","phase":"3","setting":"Men with newly diagnosed, treatment-naive unfavourable intermediate- to very-high-risk prostate cancer planned for radical prostatectomy with pelvic lymph node dissection; a staging (diagnostic) trial","sponsor":"Blue Earth Diagnostics","result":"Specificity for pelvic lymph node metastases met the pre-specified threshold (93-97% across readers) but sensitivity did not (23-30%); the agent additionally identified distant (M1) lesions, later verified true-positive in 10-15% of men (Eur Urol 2023; ASCO GU 2023)","yearReported":2023,"enrolled":356,"enrolledBasis":"registry","outcomes":[{"endpoint":"Sensitivity for pelvic lymph node metastases vs histopathology at prostatectomy","primary":true,"unit":"%","arms":[{"name":"18F-flotufolastat (rhPSMA-7.3) PET-CT","n":296,"value":27,"note":"range 23-30% across 3 readers; did not meet the 22.5% lower-CI threshold for 2 of 3 readers"}],"source":"https://pubmed.ncbi.nlm.nih.gov/37414702/"},{"endpoint":"Specificity for pelvic lymph node metastases vs histopathology at prostatectomy","primary":true,"unit":"%","arms":[{"name":"18F-flotufolastat (rhPSMA-7.3) PET-CT","n":296,"value":95,"note":"range 93-97% across 3 readers, exceeding the 82.5% pre-specified threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/37414702/"},{"endpoint":"Verified detection rate of distant (M1) lesions","unit":"%","arms":[{"name":"18F-flotufolastat PET-CT, verified by biopsy or confirmatory imaging","n":335,"value":12,"note":"range 10-15%; highest in bone (6.0-11%)"}]}],"route":"/trials/lighthouse/"}
{"id":"spotlight","kind":"trial","name":"SPOTLIGHT","aka":["18F-rhPSMA-7.3 biochemical recurrence trial"],"tldr":"A PET scan (the tracer later approved as Posluma) was tested in men whose PSA rose again after treatment for prostate cancer, to see how often it can find exactly where the cancer has come back.","summary":"SPOTLIGHT was a phase 3, prospective, multicentre, open-label, single-arm imaging trial of 18F-rhPSMA-7.3 (flotufolastat F-18, brand Posluma) in men with biochemically recurrent prostate cancer being considered for salvage therapy. Co-primary endpoints were patient-level verified detection rate and region-level positive predictive value against a composite standard of truth (histopathology where available, otherwise confirmatory imaging).\n\nOf 420 men consented, 391 received the tracer and 389 had an evaluable scan. The overall detection rate was 83%, rising from 64% at PSA below 0.5 ng/mL to 100% at higher PSA levels. The verified detection rate (51-54%) met its pre-specified threshold, but the region-level positive predictive value narrowly missed its bar when judged against the composite standard of truth; both endpoints were comfortably met in the subset with histopathology confirmation only (detection rate 81%, PPV 72%). No serious adverse events were attributed to the tracer.\n\nSPOTLIGHT and the companion LIGHTHOUSE trial in newly diagnosed disease together supported FDA approval of flotufolastat F-18 (Posluma). Post-hoc analyses have since reported performance in patients with low PSA, negative baseline conventional imaging, and in African American men.","status":"completed","asOf":"2026-09-22","links":[{"label":"Journal of Urology 2023: SPOTLIGHT primary results (Jani et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/37126069/"},{"label":"ClinicalTrials.gov: NCT04186845","url":"https://clinicaltrials.gov/study/NCT04186845"}],"tags":["diagnostic trial","prostate cancer","biochemical recurrence"],"related":["flotufolastat","psma-pet","prostate-bcr","blue-earth-diagnostics","lighthouse","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04186845","phase":"3","setting":"Men with biochemical recurrence of prostate cancer after prior curative-intent treatment, being considered for salvage therapy; a diagnostic (imaging) trial","sponsor":"Blue Earth Diagnostics","result":"Overall detection rate 83% by majority read; verified detection rate against a composite standard of truth was 51-54% across readers, meeting the pre-specified threshold, though combined region-level positive predictive value (46-60%) did not (Jani et al., J Urol 2023)","yearReported":2023,"enrolled":391,"enrolledBasis":"registry","outcomes":[{"endpoint":"Verified detection rate vs composite standard of truth (histopathology or confirmatory imaging)","primary":true,"unit":"%","arms":[{"name":"18F-flotufolastat (rhPSMA-7.3) PET-CT","n":366,"value":52,"note":"range 51-54% across 3 readers, exceeding the pre-specified threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/37126069/"},{"endpoint":"Region-level positive predictive value","primary":true,"unit":"%","arms":[{"name":"18F-flotufolastat PET-CT","n":366,"value":53,"note":"range 46-60% across readers; did not meet the pre-specified threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/37126069/"},{"endpoint":"Overall detection rate, all evaluable scans","unit":"%","arms":[{"name":"18F-flotufolastat PET-CT","n":389,"value":83,"note":"rising from 64% at PSA below 0.5 ng/mL to 100% at higher PSA"}]}],"route":"/trials/spotlight/"}
{"id":"condor","kind":"trial","name":"CONDOR","aka":["18F-DCFPyL biochemical recurrence trial"],"tldr":"A PET scan using a PSMA tracer (piflufolastat F-18, brand Pylarify) was tested in men whose prostate cancer PSA had risen again but standard scans could not find where, to see how reliably it could locate the recurrence.","summary":"CONDOR was a phase 3, prospective, multicentre, open-label, single-arm trial of 18F-DCFPyL (piflufolastat F-18, brand Pylarify) in men with biochemically recurrent prostate cancer and negative or equivocal conventional imaging (CT, MRI, bone scan, or fluciclovine/choline PET). It followed the earlier phase 2/3 OSPREY trial. The primary endpoint was correct localisation rate (CLR): positive predictive value plus a requirement that the PET-positive lesion anatomically co-localised with a composite standard of truth (histopathology, correlative imaging, or post-radiotherapy PSA response).\n\nOf 208 men enrolled (median PSA 0.8 ng/mL), the CLR was 84.8-87.0% across three independent readers, comfortably exceeding the pre-specified threshold, and performance was maintained across all three standard-of-truth categories. 18F-DCFPyL detected at least one lesion in 59-66% of patients, and the scan changed the intended management plan in 63.9% of evaluable patients, most often a shift to targeted radiotherapy.\n\nCONDOR, together with OSPREY, formed the basis of the May 2021 FDA approval of piflufolastat F-18 (Pylarify) for PSMA PET imaging in both initial high-risk staging and biochemical recurrence, one of the tracers that established PSMA PET as standard practice ahead of the confirmatory proPSMA trial.","status":"completed","asOf":"2026-09-22","links":[{"label":"Clinical Cancer Research 2021: CONDOR primary results (Morris et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/33622706/"},{"label":"ClinicalTrials.gov: NCT03739684","url":"https://clinicaltrials.gov/study/NCT03739684"}],"tags":["diagnostic trial","prostate cancer","biochemical recurrence"],"related":["pylarify","psma-pet","prostate-bcr","osprey","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03739684","phase":"3","setting":"Men with biochemically recurrent prostate cancer after radical prostatectomy or radiotherapy, with negative or equivocal conventional imaging; a diagnostic (imaging) trial","sponsor":"Progenics Pharmaceuticals","result":"Correct localisation rate 84.8-87.0% across three readers, meeting the primary endpoint; 63.9% of patients had a change in intended management after the scan (Morris et al., Clinical Cancer Research 2021)","yearReported":2021,"enrolled":208,"enrolledBasis":"registry","outcomes":[{"endpoint":"Correct localisation rate vs composite standard of truth","primary":true,"unit":"%","arms":[{"name":"18F-DCFPyL (piflufolastat F-18) PET-CT","n":208,"value":86,"note":"range 84.8-87.0% across 3 readers (lower bound of 95% CI 77.8-80.4%), meeting the pre-specified >20% threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/33622706/"},{"endpoint":"Change in intended patient management","unit":"%","arms":[{"name":"18F-DCFPyL PET-CT","value":63.9,"note":"proportion of evaluable patients with a management change after the scan"}]}],"route":"/trials/condor/"}
{"id":"osprey","kind":"trial","name":"OSPREY","aka":["18F-DCFPyL staging and recurrence trial"],"tldr":"An earlier study of the same PSMA PET scan later branded Pylarify, testing how well it detects lymph node spread before surgery in high-risk prostate cancer, and how well it confirms recurrent or spreading disease when a biopsy is possible.","summary":"OSPREY was a prospective, multicentre phase 2/3 trial of 18F-DCFPyL (piflufolastat F-18, brand Pylarify) with two cohorts. Cohort A (252 evaluable patients) evaluated sensitivity and specificity for pelvic lymph node metastases in men with high-risk prostate cancer planned for prostatectomy with lymphadenectomy, using surgical histopathology as the reference. Cohort B (93 evaluable patients) evaluated sensitivity and positive predictive value for detecting prostate cancer at sites of suspected recurrence or metastasis, verified by biopsy.\n\nIn Cohort A, specificity (97.9%) met its pre-specified threshold but sensitivity (40.3%) did not, a pattern later echoed in LIGHTHOUSE and consistent with the difficulty PSMA PET has detecting small-volume nodal disease. In Cohort B, sensitivity (95.8%) and positive predictive value (81.9%) for extraprostatic lesions were high. The tracer was well tolerated, with drug-related adverse events in 7.0% of patients.\n\nOSPREY was the earlier of the two pivotal trials (with CONDOR) supporting the May 2021 FDA approval of piflufolastat F-18 (Pylarify).","status":"completed","asOf":"2026-09-22","links":[{"label":"J Urol 2021: OSPREY primary results (Pienta et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/33634707/"},{"label":"ClinicalTrials.gov: NCT02981368","url":"https://clinicaltrials.gov/study/NCT02981368"}],"tags":["diagnostic trial","prostate cancer","staging"],"related":["pylarify","psma-pet","prostate-high-risk","condor","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02981368","phase":"2/3","setting":"Cohort A: men with high-risk prostate cancer planned for radical prostatectomy with lymphadenectomy (initial staging). Cohort B: men with suspected recurrent or metastatic prostate cancer feasible for biopsy","sponsor":"Progenics Pharmaceuticals","result":"Cohort A: specificity 97.9% met the primary endpoint but sensitivity 40.3% did not; Cohort B: sensitivity 95.8% and PPV 81.9% for extraprostatic lesions (Pienta et al., J Urol 2021)","yearReported":2021,"enrolled":385,"enrolledBasis":"registry","outcomes":[{"endpoint":"Specificity for pelvic nodal disease, Cohort A, vs histopathology at prostatectomy","primary":true,"unit":"%","arms":[{"name":"18F-DCFPyL PET-CT","n":252,"value":97.9,"note":"median 95% CI 94.5-99.4% across 3 readers, meeting the pre-specified threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/33634707/"},{"endpoint":"Sensitivity for pelvic nodal disease, Cohort A, vs histopathology","primary":true,"unit":"%","arms":[{"name":"18F-DCFPyL PET-CT","n":252,"value":40.3,"note":"median 95% CI 28.1-52.5%; did not meet the pre-specified threshold"}],"source":"https://pubmed.ncbi.nlm.nih.gov/33634707/"},{"endpoint":"Sensitivity for extraprostatic lesions, Cohort B, vs biopsy","unit":"%","arms":[{"name":"18F-DCFPyL PET-CT","n":93,"value":95.8,"note":"median 95% CI 87.8-99.0%; PPV 81.9%"}]}],"route":"/trials/osprey/"}
{"id":"falcon","kind":"trial","name":"FALCON","aka":["18F-fluciclovine biochemical recurrence management trial"],"tldr":"A PET scan using the tracer fluciclovine (brand Axumin) was tested in UK men whose prostate cancer PSA had risen again, to see how often the scan changed the treatment doctors planned to give.","summary":"FALCON was a UK-based, prospective, multicentre, open-label phase 3 trial of 18F-fluciclovine PET-CT (Axumin) jointly funded by Innovate UK and Blue Earth Diagnostics, run across six NHS sites. It enrolled men with a first episode of biochemical recurrence after curative-intent therapy who were being considered for salvage treatment. The primary endpoint was the proportion of patients whose documented management plan changed after the scan, comparing pre-scan and post-scan plans recorded by treating clinicians.\n\nAmong 104 scanned patients (median PSA 0.79 ng/mL), lesions were detected in 56%, with detection rising with PSA. A management change occurred in 64% (66/104) of patients, 65% of these classed as major (a change in treatment modality, such as salvage or systemic therapy to watchful waiting, or vice versa); the remainder were adjustments within a modality, commonly a fluciclovine-guided radiotherapy boost. A pre-planned interim analysis stopped recruitment early on efficacy grounds. A related secondary analysis found that outcomes tended to be better when salvage therapy was guided by a positive scan.\n\nFALCON, alongside the US LOCATE trial, supported the clinical adoption of fluciclovine PET for biochemical recurrence, and its subgroup work on salvage radiotherapy planning fed into later evidence (including a separate randomised trial) showing improved failure-free survival when radiotherapy fields were guided by fluciclovine PET rather than conventional imaging.","status":"completed","asOf":"2026-09-22","links":[{"label":"Int J Radiat Oncol Biol Phys 2020: FALCON primary results (Scarsbrook et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/32068113/"},{"label":"ClinicalTrials.gov: NCT02578940","url":"https://clinicaltrials.gov/study/NCT02578940"},{"label":"Blue Earth Diagnostics: FALCON trial results announcement","url":"https://www.blueearthdiagnostics.com/hubfs/PR063.pdf"}],"tags":["diagnostic trial","prostate cancer","biochemical recurrence","management impact"],"related":["fluciclovine-f18","prostate-bcr","blue-earth-diagnostics","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02578940","phase":"3","setting":"Men with a first episode of biochemical recurrence of prostate cancer after curative-intent primary therapy, being considered for salvage therapy; a diagnostic (management-impact) trial","sponsor":"Blue Earth Diagnostics","result":"64% (66/104) of patients had a management plan change after 18F-fluciclovine PET-CT, 65% of those major (e.g. a switch in treatment modality); lesions were detected in 56% of scans (Scarsbrook et al., Int J Radiat Oncol Biol Phys 2020)","yearReported":2019,"enrolled":104,"enrolledBasis":"registry","outcomes":[{"endpoint":"Proportion of patients with a revised management plan (pre-scan vs post-scan)","primary":true,"unit":"%","arms":[{"name":"18F-fluciclovine PET-CT","n":104,"value":64,"note":"66/104; recruitment stopped early for overwhelming efficacy at a planned interim analysis"}],"source":"https://pubmed.ncbi.nlm.nih.gov/32068113/"},{"endpoint":"Detection rate","unit":"%","arms":[{"name":"18F-fluciclovine PET-CT","n":104,"value":56,"note":"58/104 patients had at least one avid lesion; 93% of scans positive at PSA >2.0 ng/mL"}]}],"route":"/trials/falcon/"}
{"id":"upfront-psma","kind":"trial","name":"UpFrontPSMA","aka":["ANZUP sequential LuPSMA and docetaxel trial"],"tldr":"In men newly diagnosed with prostate cancer that has already spread widely, giving two doses of the radioactive drug lutetium-PSMA before starting chemotherapy cleared PSA to undetectable levels in more men than chemotherapy alone, without adding side effects.","summary":"UpFrontPSMA was an investigator-initiated, open-label, randomised phase 2 trial run at 11 Australian hospitals by the Peter MacCallum Cancer Centre and ANZUP, testing 177Lu-PSMA-617 given before docetaxel in men with de novo, high-volume, PSMA-avid metastatic hormone-sensitive prostate cancer starting androgen deprivation therapy. Patients were randomised 1:1 to two cycles of 177Lu-PSMA-617 (7.5 GBq every 6 weeks) followed six weeks later by six cycles of docetaxel, or to six cycles of docetaxel alone, both with continuous ADT. The primary endpoint was the proportion with undetectable PSA (≤0.2 ng/mL) at 48 weeks.\n\nAmong 130 randomised patients (122 evaluable), the LuPSMA-then-docetaxel sequence produced undetectable PSA in 41% versus 16% with docetaxel alone, and improved PSA progression-free survival (31 vs 20 months) and freedom from castration resistance (20 vs 16 months), with grade 3-4 toxicity comparable between arms (29% vs 27%) and no treatment-related deaths.\n\nUpFrontPSMA is the first randomised evidence that adding LuPSMA before chemotherapy can deepen responses in newly diagnosed, high-volume hormone-sensitive disease, a different sequencing strategy from the phase 3 PSMAddition trial (which added LuPSMA to an ARPI rather than to chemotherapy). Overall survival data are still immature; the trial is registered as active, not recruiting, and follow-up continues.","status":"active","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2024: UpFrontPSMA primary results (Azad et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/39293461/"},{"label":"ClinicalTrials.gov: NCT04343885","url":"https://clinicaltrials.gov/study/NCT04343885"},{"label":"ANZUP: UpFrontPSMA trial page","url":"https://anzup.org.au/clinical-trial/upfrontpsma-trial/"}],"tags":["radioligand therapy","prostate cancer","hormone-sensitive","first line"],"related":["pluvicto","docetaxel","prostate-mhspc","psmaddition","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04343885","phase":"2","setting":"De novo, high-volume metastatic hormone-sensitive prostate cancer, first-line, given within 12 weeks of diagnosis and no more than 4 weeks of androgen deprivation therapy","sponsor":"Peter MacCallum Cancer Centre / ANZUP Cancer Trials Group","result":"41% undetectable PSA at 48 weeks with sequential 177Lu-PSMA-617 then docetaxel vs 16% with docetaxel alone (OR 3.88, 95% CI 1.61-9.38, p=0.002); PSA progression-free survival 31 vs 20 months (HR 0.60, 95% CI 0.37-0.98, p=0.039) (Azad et al., Lancet Oncology 2024)","yearReported":2024,"enrolled":130,"enrolledBasis":"registry","outcomes":[{"endpoint":"Undetectable PSA (≤0.2 ng/mL) at 48 weeks","primary":true,"unit":"%","arms":[{"name":"177Lu-PSMA-617 (2 cycles) then docetaxel (6 cycles) + ADT","n":61,"value":41,"note":"25/61, 95% CI 30-54"},{"name":"Docetaxel (6 cycles) + ADT alone","n":61,"value":16,"note":"10/61, 95% CI 9-28"}],"p":"0.0020","source":"https://pubmed.ncbi.nlm.nih.gov/39293461/"},{"endpoint":"PSA progression-free survival","unit":"months","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":31},{"name":"Docetaxel + ADT alone","value":20}],"hr":0.6,"ci":[0.37,0.98],"p":"0.039"},{"endpoint":"Freedom from castration resistance","unit":"months","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":20},{"name":"Docetaxel + ADT alone","value":16}],"hr":0.6,"ci":[0.38,0.96],"p":"0.033"},{"endpoint":"Grade 3-4 treatment-related adverse events","unit":"%","arms":[{"name":"177Lu-PSMA-617 then docetaxel + ADT","value":29},{"name":"Docetaxel + ADT alone","value":27}],"source":"https://pubmed.ncbi.nlm.nih.gov/39293461/"}],"route":"/trials/upfront-psma/"}
{"id":"enza-p","kind":"trial","name":"ENZA-p","aka":["ANZUP 1901"],"tldr":"Adding the radioactive drug lutetium-PSMA to the hormone drug enzalutamide, with the dose adjusted according to a mid-treatment PET scan, kept prostate cancer under control for longer and helped men with high-risk metastatic disease live longer than enzalutamide on its own.","summary":"ENZA-p (ANZUP 1901) was an open-label, randomised, controlled phase 2 trial at 15 Australian hospitals in men with metastatic castration-resistant prostate cancer who had not yet received docetaxel or an androgen receptor pathway inhibitor for mCRPC, had PSMA-PET-positive disease, and carried at least two risk factors for early progression on enzalutamide. Patients received oral enzalutamide alone or with adaptive-dosed intravenous 177Lu-PSMA-617 (two or four cycles of 7.5 GBq every 6-8 weeks, guided by an interim PSMA PET-CT at week 12). The primary endpoint was PSA progression-free survival.\n\nAmong 162 randomised patients, adding LuPSMA improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and PSA response rate (93% vs 68%) at the interim analysis. At longer follow-up (median 34 months), overall survival also favoured the combination (median 34 vs 26 months, HR 0.55, p=0.0053), along with better quality-of-life deterioration-free survival for physical function and overall health. Grade 3-5 adverse events were comparable between arms, with anaemia and thrombocytopenia occurring only in the combination group; there were no treatment-related deaths.\n\nENZA-p is the first randomised trial to show an overall survival benefit for adding LuPSMA to an ARPI ahead of chemotherapy, using biomarker-guided adaptive dosing via interim PSMA PET, and it has prompted phase 3 evaluation of the same combination strategy.","status":"active","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2024: ENZA-p interim results","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00135-9/abstract"},{"label":"Lancet Oncology 2025: ENZA-p overall survival and quality of life (secondary outcomes)","url":"https://pubmed.ncbi.nlm.nih.gov/39956124/"},{"label":"ClinicalTrials.gov: NCT04419402","url":"https://clinicaltrials.gov/study/NCT04419402"}],"tags":["radioligand therapy","prostate cancer","combination therapy","adaptive dosing"],"related":["pluvicto","enzalutamide","prostate-mcrpc","psma-pet","psmafore","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04419402","phase":"2","setting":"Metastatic castration-resistant prostate cancer, PSMA-PET-positive, no prior docetaxel or ARPI for mCRPC, with at least two risk factors for early progression on enzalutamide; first-line mCRPC","sponsor":"Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)","result":"Adding adaptive-dosed 177Lu-PSMA-617 to enzalutamide improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43, p<0.0001) and, at longer follow-up, overall survival (median 34 vs 26 months, HR 0.55, 95% CI 0.36-0.84, p=0.0053) (Lancet Oncology 2024 and 2025)","yearReported":2025,"enrolled":162,"enrolledBasis":"registry","outcomes":[{"endpoint":"PSA progression-free survival","primary":true,"unit":"months","arms":[{"name":"Enzalutamide + adaptive-dosed 177Lu-PSMA-617","n":83,"value":13},{"name":"Enzalutamide alone","n":79,"value":7.8}],"hr":0.43,"ci":[0.29,0.63],"p":"<0.0001","source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00135-9/abstract"},{"endpoint":"Overall survival (longer follow-up)","unit":"months","arms":[{"name":"Enzalutamide + adaptive-dosed 177Lu-PSMA-617","n":83,"value":34},{"name":"Enzalutamide alone","n":79,"value":26}],"hr":0.55,"ci":[0.36,0.84],"p":"0.0053","source":"https://pubmed.ncbi.nlm.nih.gov/39956124/"},{"endpoint":"PSA response rate (≥50% decline)","unit":"%","arms":[{"name":"Enzalutamide + 177Lu-PSMA-617","n":83,"value":93},{"name":"Enzalutamide alone","n":79,"value":68}]},{"endpoint":"Grade 3-5 adverse events (secondary-outcomes report)","unit":"%","arms":[{"name":"Enzalutamide + 177Lu-PSMA-617","n":81,"value":46},{"name":"Enzalutamide alone","n":79,"value":44}],"source":"https://pubmed.ncbi.nlm.nih.gov/39956124/"}],"route":"/trials/enza-p/"}
{"id":"lutectomy","kind":"trial","name":"LuTectomy","aka":["Neoadjuvant 177Lu-PSMA-617 before radical prostatectomy"],"tldr":"In men about to have their prostate removed for high-risk cancer, giving one or two doses of the radioactive drug lutetium-PSMA beforehand delivered a meaningful radiation dose straight to the tumour, was well tolerated, and did not make the surgery harder or riskier.","summary":"LuTectomy was a single-centre, single-arm phase 1/2 study at the Peter MacCallum Cancer Centre investigating neoadjuvant 177Lu-PSMA-617 in men with high-risk localised prostate cancer (PSA >20 ng/mL, ISUP grade group 3-5, or ≥cT2c) with high tumour uptake on 68Ga-PSMA-11 PET, scheduled for robotic radical prostatectomy. Cohort A (n=10) received one cycle and cohort B (n=10) received two cycles of 177Lu-PSMA-617 (5 GBq), with surgery six weeks after the last dose. The primary endpoint was tumour radiation absorbed dose, measured by three-timepoint SPECT-CT dosimetry.\n\nAcross 20 patients, the treatment delivered a median highest-lesion dose of 35.5 Gy (19.6 Gy to the prostate, with lymph node doses up to a median of 38-48 Gy in relevant patients), and 45% achieved a PSA decline of 50% or more. Toxicity was low grade only (fatigue, nausea, dry mouth, mild thrombocytopenia), with no grade 3-4 events and no Clavien-Dindo grade 3-5 surgical complications; surgeons reported no unexpected intraoperative difficulty. On pathology, 80% of specimens showed a partial histological response, but no patient achieved a complete pathological response.\n\nLuTectomy is one of the first trials to test PSMA radioligand therapy in the neoadjuvant, potentially curative setting rather than in metastatic disease. It establishes feasibility and biological activity but not yet a benefit in metastasis-free or overall survival; larger trials of multi-cycle or combination regimens are the logical next step, and neoadjuvant PSMA radioligand therapy is not currently part of any clinical guideline.","status":"active","asOf":"2026-09-22","links":[{"label":"European Urology 2024: LuTectomy primary results (Eapen et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/37891072/"},{"label":"ClinicalTrials.gov: NCT04430192","url":"https://clinicaltrials.gov/study/NCT04430192"}],"tags":["radioligand therapy","prostate cancer","neoadjuvant","dosimetry"],"related":["pluvicto","prostate-high-risk","prostatectomy","psma-pet","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04430192","phase":"1/2","setting":"Men with high-risk localised prostate cancer and high PSMA uptake, scheduled for radical prostatectomy; neoadjuvant, pre-surgical setting","sponsor":"Peter MacCallum Cancer Centre, Australia","result":"A single dose of neoadjuvant 177Lu-PSMA-617 delivered a median tumour absorbed dose of 35.5 Gy (19.6 Gy to the prostate), with 45% of patients achieving a >50% PSA decline; no grade 3/4 toxicity and no surgical complications attributable to the drug (Eapen et al., Eur Urol 2024)","yearReported":2023,"enrolled":20,"enrolledBasis":"registry","outcomes":[{"endpoint":"Highest tumour radiation absorbed dose after cycle 1","primary":true,"unit":"Gy","arms":[{"name":"177Lu-PSMA-617 (5 GBq), one or two cycles before prostatectomy","n":20,"value":35.5,"note":"median, IQR 19.5-50.1; 19.6 Gy (IQR 11.3-48.4) delivered to the prostate specifically"}],"source":"https://pubmed.ncbi.nlm.nih.gov/37891072/"},{"endpoint":"PSA50 response","unit":"%","arms":[{"name":"177Lu-PSMA-617 before prostatectomy","n":20,"value":45,"note":"9/20 patients achieved a >50% PSA decline"}]},{"endpoint":"Pathological complete response","unit":"%","arms":[{"name":"177Lu-PSMA-617 before prostatectomy","n":20,"value":0,"note":"0 of 20 patients; 80% showed a partial histological response (fibrosis, reduced tumour cell density)"}]},{"endpoint":"Grade 3/4 toxicity and Clavien-Dindo grade 3-5 surgical complications","unit":"%","arms":[{"name":"177Lu-PSMA-617 before prostatectomy","n":20,"value":0,"note":"none observed; surgery was feasible and safe in all patients"}]}],"route":"/trials/lutectomy/"}
{"id":"prince-trial","kind":"trial","name":"PRINCE","aka":["PSMA-lutetium Radionuclide Therapy and ImmuNotherapy in Prostate CancEr"],"tldr":"Combining the radioactive drug lutetium-PSMA with the immunotherapy drug pembrolizumab produced strong PSA responses in men with advanced, heavily pretreated prostate cancer, with side effects in line with what each drug causes on its own.","summary":"PRINCE was a single-arm, multicentre phase 1b/2 trial led by the Peter MacCallum Cancer Centre, testing whether adding the checkpoint inhibitor pembrolizumab to 177Lu-PSMA-617 could improve on radioligand therapy alone in metastatic castration-resistant prostate cancer, a disease with generally low response to immunotherapy alone. Eligible men had progressed on an androgen receptor pathway inhibitor (prior docetaxel allowed) and had high PSMA expression on PET. Participants received up to six cycles of 177Lu-PSMA-617 every six weeks with pembrolizumab 200 mg every three weeks for up to 24 months. Co-primary endpoints were safety and PSA50 response rate.\n\nAmong 37 participants (73% docetaxel-pretreated, 100% ARPI-pretreated), a PSA decline of 50% or more was seen in 76%, and 46% had a PSA decline of 90% or more. In the subset with measurable disease, the objective response rate was 70%. Median overall survival was 20.8 months. Toxicity was consistent with the known profiles of each drug: xerostomia, fatigue and pruritus were common but mostly grade 1-2, while grade 3 immune-related adverse events (colitis, pancreatitis, myasthenia gravis, and others attributable to pembrolizumab) occurred in 30% of patients; there were no grade 4 events or treatment-related deaths.\n\nPRINCE reports encouraging activity and manageable toxicity for the combination, broadly in line with 177Lu-PSMA-617 monotherapy benchmarks from VISION, and the authors conclude that radioligand therapy remains the principal driver of response with pembrolizumab possibly adding benefit in a biologically susceptible subset. It is a single-arm, non-randomised study, so it cannot establish incremental benefit from adding pembrolizumab.","status":"completed","asOf":"2026-09-22","links":[{"label":"Lancet Oncology 2026: PRINCE final results (Sandhu et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/41926961/"},{"label":"ClinicalTrials.gov: NCT03658447","url":"https://clinicaltrials.gov/study/NCT03658447"}],"tags":["radioligand therapy","prostate cancer","immunotherapy combination"],"related":["pluvicto","pembrolizumab","prostate-mcrpc","psma-pet","vision","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03658447","phase":"1/2","setting":"Metastatic castration-resistant prostate cancer with high PSMA expression, after prior androgen receptor pathway inhibitor (with prior docetaxel allowed); combination therapy trial","sponsor":"Peter MacCallum Cancer Centre, Australia","result":"76% (28/37) of patients achieved a PSA50 response with 177Lu-PSMA-617 plus pembrolizumab; median overall survival 20.8 months; grade 3 immune-related adverse events occurred in 30% of patients, with no grade 4 events or treatment-related deaths (Sandhu et al., Lancet Oncology 2026)","yearReported":2026,"enrolled":37,"enrolledBasis":"registry","outcomes":[{"endpoint":"PSA50 response rate (co-primary with safety)","primary":true,"unit":"%","arms":[{"name":"177Lu-PSMA-617 (up to 6 cycles) + pembrolizumab (up to 24 months)","n":37,"value":76,"note":"28/37, 95% CI 59-88; 46% had a PSA90 response"}],"source":"https://pubmed.ncbi.nlm.nih.gov/41926961/"},{"endpoint":"Objective response rate (RECIST-evaluable subset)","unit":"%","arms":[{"name":"177Lu-PSMA-617 + pembrolizumab","n":10,"value":70,"note":"7/10 patients with measurable disease"}]},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"177Lu-PSMA-617 + pembrolizumab","n":37,"value":20.8,"note":"95% CI 13.5-not estimable"}]},{"endpoint":"Grade 3 immune-related adverse events","unit":"%","arms":[{"name":"177Lu-PSMA-617 + pembrolizumab","n":37,"value":30,"note":"colitis, fatigue, amylase rise, and others; no grade 4 events or treatment-related deaths"}]}],"route":"/trials/prince-trial/"}
{"id":"aurora-flurpiridaz","kind":"trial","name":"AURORA","aka":["International Study to Evaluate Diagnostic Efficacy of Flurpiridaz (18F) Injection PET MPI"],"tldr":"A new PET heart-imaging tracer called flurpiridaz was tested against the standard SPECT heart scan in people with suspected coronary artery disease, and found blocked arteries more reliably, especially in women and people with obesity, while using about half the radiation dose.","summary":"AURORA was the second (confirmatory) phase 3, prospective, multicentre trial of 18F-flurpiridaz, a novel PET myocardial perfusion imaging tracer, following an earlier phase 3 study that met its sensitivity endpoint but not its specificity non-inferiority criterion. AURORA enrolled 730 patients with suspected coronary artery disease across 48 sites in the US, Canada, and Europe; 578 were evaluable. Each patient underwent same-day rest/stress flurpiridaz PET and rest-stress 99mTc-labelled SPECT, both read blinded by three experts, before invasive coronary angiography (ICA) as the reference standard for ≥50% stenosis.\n\nFlurpiridaz PET met both co-primary efficacy endpoints: sensitivity was higher than SPECT (80.3% vs 68.7%, p=0.0003) and specificity was non-inferior (63.8% vs 61.7%, p=0.0004). The area under the receiver-operating-characteristic curve favoured PET overall (0.80 vs 0.68) and specifically in women and obese patients, two groups in whom SPECT image quality is often degraded by attenuation artefact. PET also reduced radiation exposure by roughly half compared with SPECT and improved image quality and diagnostic certainty. A prespecified obesity subgroup analysis published in 2026 confirmed the advantage held across BMI categories.\n\nAURORA supported FDA approval of flurpiridaz F-18 for PET myocardial perfusion imaging, giving cardiac PET a second widely available perfusion tracer alongside rubidium-82 and expanding access to PET myocardial perfusion imaging at centres with an on-site or nearby cyclotron rather than a generator.","status":"completed","asOf":"2026-09-22","links":[{"label":"JACC 2023: AURORA primary results (Maddahi et al.)","url":"https://pubmed.ncbi.nlm.nih.gov/37821170/"},{"label":"ClinicalTrials.gov: NCT03354273","url":"https://clinicaltrials.gov/study/NCT03354273"}],"tags":["diagnostic trial","cardiology","PET tracer","myocardial perfusion"],"related":["pet","pet-tracer-manufacturing","f-18","tc-99m","rb-82"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03354273","phase":"3","setting":"Adults with suspected coronary artery disease undergoing myocardial perfusion imaging before invasive coronary angiography; a diagnostic (cardiac imaging) trial","sponsor":"GE HealthCare","result":"18F-flurpiridaz PET was more sensitive than 99mTc-SPECT for detecting ≥50% coronary stenosis (80.3% vs 68.7%, p=0.0003) with non-inferior specificity (63.8% vs 61.7%, p=0.0004), meeting both primary efficacy endpoints (Maddahi et al., JACC 2023)","yearReported":2023,"enrolled":730,"enrolledBasis":"registry","outcomes":[{"endpoint":"Sensitivity for coronary artery disease (≥50% stenosis by quantitative coronary angiography)","primary":true,"unit":"%","arms":[{"name":"18F-flurpiridaz PET","n":578,"value":80.3},{"name":"99mTc-SPECT","n":578,"value":68.7}],"p":"0.0003","source":"https://pubmed.ncbi.nlm.nih.gov/37821170/"},{"endpoint":"Specificity for coronary artery disease","primary":true,"unit":"%","arms":[{"name":"18F-flurpiridaz PET","n":578,"value":63.8},{"name":"99mTc-SPECT","n":578,"value":61.7}],"p":"0.0004","source":"https://pubmed.ncbi.nlm.nih.gov/37821170/"},{"endpoint":"Area under the ROC curve, overall population","unit":"AUC","arms":[{"name":"18F-flurpiridaz PET","value":0.8},{"name":"99mTc-SPECT","value":0.68}],"p":"<0.001"}],"route":"/trials/aurora-flurpiridaz/"}
{"id":"ideas-amyloid","kind":"trial","name":"IDEAS (Imaging Dementia-Evidence for Amyloid Scanning)","aka":["IDEAS study"],"tldr":"A large US Medicare study asked whether a brain scan that detects amyloid protein (a hallmark of Alzheimer's disease) actually changes what doctors do for patients with memory problems; it found that doctors changed the treatment or diagnosis plan for roughly six in ten patients after seeing the scan.","summary":"IDEAS was a single-group, multisite, longitudinal observational study run by the American College of Radiology under Medicare's Coverage with Evidence Development programme, designed to determine whether amyloid PET changes clinical management in Medicare beneficiaries with mild cognitive impairment (MCI) or dementia of uncertain aetiology who met published appropriate-use criteria. Dementia specialists recorded an intended management plan before amyloid PET and again 90 days after, covering Alzheimer's disease drug therapy, other drug therapy, and safety/future-planning counselling; the study was powered to detect a 30% or greater change in each of the MCI and dementia groups.\n\nOf 18,488 registered participants, 11,409 were included in the primary analysis (6,905 with MCI, 4,504 with dementia). The composite management endpoint changed in 60.2% of the MCI group and 63.5% of the dementia group, both far exceeding the 30% target; Alzheimer's disease drug use changed most often. The aetiological diagnosis flipped from Alzheimer's to non-Alzheimer's disease in 25.1% of patients and the reverse in 10.5%. A later health-utilisation analysis found a smaller-than-hoped 4.5% relative reduction in 12-month hospitalisations, short of the pre-specified 10% effect size, though patients with positive scans were hospitalised less often than those with negative scans.\n\nIDEAS is a management-impact study, not a trial of clinical outcomes from a therapeutic intervention, and it predates the era of anti-amyloid disease-modifying drugs (lecanemab, donanemab), which have since made amyloid status a treatment-eligibility gate rather than only a diagnostic aid. Its results, together with the follow-on New IDEAS study (NCT04426539), underpinned the 2023 removal of the Medicare national coverage determination that had required amyloid PET to be performed only within an approved research study.","status":"completed","asOf":"2026-09-22","links":[{"label":"JAMA 2019: IDEAS primary results (Rabinovici et al.)","url":"https://jamanetwork.com/journals/jama/fullarticle/2729371"},{"label":"ClinicalTrials.gov: NCT02420756","url":"https://clinicaltrials.gov/study/NCT02420756"},{"label":"CMS: amyloid PET national coverage determination removal decision memo","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=308"}],"tags":["diagnostic trial","neurology","amyloid PET","coverage with evidence development"],"related":["medicare-ced"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02420756","phase":"observational","setting":"Medicare beneficiaries with mild cognitive impairment or dementia of uncertain cause, evaluated by dementia specialists; a coverage-with-evidence-development registry study, not a treatment trial","sponsor":"American College of Radiology","result":"Amyloid PET changed the composite management plan (drug therapy or counselling) within 90 days in 60.2% of patients with mild cognitive impairment and 63.5% of patients with dementia of uncertain cause, both far exceeding the pre-specified 30% threshold, among 11,409 analysed patients (Rabinovici et al., JAMA 2019)","yearReported":2019,"enrolled":18488,"enrolledBasis":"registered","enrolledNote":"Registry enrolment (18,488) is the total registered; the JAMA 2019 primary management-change analysis was on 11,409 patients with complete pre- and post-scan data.","outcomes":[{"endpoint":"Change in composite patient management plan within 90 days, mild cognitive impairment group","primary":true,"unit":"%","arms":[{"name":"Pre-PET vs post-PET documented plan (MCI)","n":6905,"value":60.2,"note":"95% CI 59.1-61.4%, exceeding the pre-specified 30% threshold, p<0.001"}],"source":"https://jamanetwork.com/journals/jama/fullarticle/2729371"},{"endpoint":"Change in composite patient management plan within 90 days, dementia of uncertain cause group","primary":true,"unit":"%","arms":[{"name":"Pre-PET vs post-PET documented plan (dementia)","n":4504,"value":63.5,"note":"95% CI 62.1-64.9%, exceeding the pre-specified 30% threshold, p<0.001"}],"source":"https://jamanetwork.com/journals/jama/fullarticle/2729371"},{"endpoint":"Change in aetiological diagnosis","unit":"%","arms":[{"name":"Amyloid PET, all patients","n":11409,"value":25.1,"note":"changed from Alzheimer's disease to non-Alzheimer's; 10.5% changed the other way"}]}],"route":"/trials/ideas-amyloid/"}