[{"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},{"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"},{"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"},{"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"},{"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"]},{"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"]},{"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"]},{"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"},{"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)"]},{"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"},{"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},{"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},{"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},{"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"},{"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},{"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"]},{"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},{"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},{"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"},{"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},{"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"},{"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"]},{"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},{"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},{"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},{"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"},{"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"]},{"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},{"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"},{"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"},{"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"]},{"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"]},{"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},{"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"]},{"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},{"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"]},{"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},{"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},{"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},{"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"},{"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},{"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},{"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"},{"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"]},{"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},{"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"},{"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},{"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"},{"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"]},{"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"]},{"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},{"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"]},{"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"]},{"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},{"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"]},{"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},{"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"},{"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"]},{"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},{"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"]},{"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"},{"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},{"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."]},{"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"]},{"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"},{"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"]},{"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"]},{"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"]},{"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}]