[{"id":"paper-kratochwil-ac225-psma-jnm-2016","kind":"paper","name":"225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer","aka":[],"tldr":"The first published report of two men with very advanced prostate cancer, who had run out of other options, having their cancer disappear on scans after treatment with an alpha-emitting radioactive drug aimed at PSMA.","summary":"This case report from Heidelberg described the first-in-human use of 225Ac-PSMA-617, an alpha-particle-emitting version of the PSMA-617 ligand used with the beta-emitter lutetium-177. Two men with metastatic castration-resistant prostate cancer in clinically critical situations - one for whom beta-emitter therapy was contraindicated by diffuse bone marrow infiltration, one who had become resistant to 177Lu-PSMA-617 - were treated with 100 kBq of 225Ac-PSMA-617 per kilogram of body weight, given roughly every two months, after 68Ga-PSMA-11 PET/CT confirmed a PSMA-positive tumour phenotype.\n\nBoth patients had PSA fall to below the detectable level and achieved a complete response on repeat 68Ga-PSMA-11 PET/CT imaging, with no relevant haematological toxicity. Xerostomia (dry mouth), from radiation to the salivary glands (which also express PSMA), was the only notable side effect.\n\nAlthough based on only two patients, this report is widely cited as the proof of concept that launched clinical development of actinium-225-labelled PSMA radioligands as a next-generation, more potent alternative to beta-emitter therapy for men who fail or cannot tolerate 177Lu-PSMA-617. It also flagged salivary gland toxicity as the principal dose-limiting problem for PSMA-targeted alpha therapy, a theme followed up in the authors' subsequent dosimetry and dose-finding papers (2017, 2018).","asOf":"2026-09-22","links":[{"label":"JNM: 225Ac-PSMA-617 first-in-human report (full text PDF)","url":"https://jnm.snmjournals.org/content/jnumed/57/12/1941.full.pdf"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/27389577/"}],"tags":["alpha therapy","prostate cancer","first-in-human"],"related":["ac225-psma","targeted-alpha-therapy","psma","prostate-mcrpc","clemens-kratochwil","uwe-haberkorn","beta-then-alpha","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2016,"doi":"10.2967/jnumed.116.178673","pmid":"27389577","authors":"Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, et al.","paperType":"observational","findings":["Both patients achieved a PSA decline to below the measurable level and a complete response on 68Ga-PSMA-11 PET/CT restaging.","No relevant haematological toxicity was observed at 100 kBq/kg per cycle, dosed roughly every 8 weeks.","Xerostomia was the only notable clinical side effect reported."],"whatItMeans":"This was the first evidence, in two patients, that attaching a more powerful (alpha-emitting) form of radiation to the same PSMA-seeking molecule used in lutetium-177 PSMA therapy could produce a complete response even in prostate cancer that had already stopped responding to the beta-emitter version.","caveats":["Only two patients; no control group, no survival data, and no formal toxicity study - this is hypothesis-generating, not proof of benefit.","225Ac-PSMA-617 remains investigational; as of this record's date it had not been approved by FDA or EMA and is used mainly under compassionate access or in trials.","Long-term xerostomia and renal toxicity risks were characterised in later, larger series, not in this initial report."],"changedPractice":false,"participants":2},{"id":"paper-alsympca-radium-223-nejm-2013","kind":"paper","name":"ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases","aka":[],"tldr":"Radium-223, an injected alpha-emitting radioisotope that homes to bone, lengthened survival and delayed skeletal complications in men with castration-resistant prostate cancer that had spread to bone but not to organs.","summary":"Phase 3 placebo-controlled trial of 921 men with castration-resistant prostate cancer, symptomatic bone metastases and no visceral disease, randomised 2:1 to six injections of radium-223 or placebo with best standard of care.\n\nMedian overall survival was 14.9 versus 11.3 months (hazard ratio 0.70), time to first symptomatic skeletal event was delayed (15.6 versus 9.8 months) and myelosuppression was mild.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1213755"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23863050/"}],"tags":[],"related":["ra-223"],"indications":["prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca"],"people":["chris-parker"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1213755","pmid":"23863050","authors":"Parker C, Nilsson S, Heinrich D, et al.","paperType":"rct","findings":["Median overall survival 14.9 vs 11.3 months; hazard ratio 0.70.","Time to first symptomatic skeletal event 15.6 vs 9.8 months."],"whatItMeans":"Radium-223 is an option for symptomatic bone-predominant castration-resistant prostate cancer, now less used since lutetium-PSMA, and should not be combined with abiraterone after the ERA 223 fracture signal.","caveats":["No effect on PSA or soft tissue disease.","Combination with abiraterone increased fractures and deaths in ERA 223."],"changedPractice":true,"participants":921},{"id":"paper-jadvar-snmmi-psma-auc-jnm-2022","kind":"paper","name":"Appropriate use criteria for prostate-specific membrane antigen (PSMA) PET imaging","aka":[],"tldr":"A panel of cancer and imaging specialists agreed, scenario by scenario, when a PSMA PET scan for prostate cancer is a good idea and when it usually is not - a reference clinicians and insurers use to decide who should get the scan.","summary":"Following FDA approval of the first PSMA PET tracers (68Ga-PSMA-11 and 18F-DCFPyL) in 2020-2021, SNMMI convened a multidisciplinary panel - with the American College of Nuclear Medicine, American Urological Association, ANZSNM, ASCO, EANM and American College of Physicians - to produce appropriate use criteria (AUC) for PSMA PET in prostate cancer, using a RAND/UCLA-style consensus process. The panel scored defined clinical scenarios from 1 (rarely appropriate) to 9 (appropriate).\n\nPSMA PET was rated appropriate (score 8-9) for staging newly diagnosed unfavourable-intermediate, high- or very-high-risk prostate cancer (including when conventional imaging is negative or equivocal), for working up a PSA rise after prostatectomy or radiotherapy (biochemical recurrence), for non-metastatic castration-resistant disease on conventional imaging, and - critically - for confirming eligibility for PSMA-targeted radioligand therapy (score 9). It was rated rarely appropriate (score 2-3) for detecting or characterising the primary tumour in men with suspected but unbiopsied prostate cancer, or in very low/low/favourable-intermediate risk disease.\n\nThe document became the reference used by payers and referring clinicians to decide when a PSMA PET scan is billable and clinically justified, and its scenario 11 (eligibility for PSMA radioligand therapy) directly operationalises how VISION- and TheraP-style PET selection criteria are applied in routine practice.","asOf":"2026-09-22","links":[{"label":"SNMMI: PSMA PET Appropriate Use Criteria (PDF)","url":"https://snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Appropriate%20Use%20Criteria/PSMA%20AUC%202022.03.15_final_BOD%20approved.pdf"},{"label":"SNMMI: AUC overview page","url":"https://snmmi.org/Web/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate-Use-Criteria-for-Prostate-Specific-Membrane-Antigen--PSMA--PET-Imaging.aspx"}],"tags":["guideline","PSMA PET","appropriate use criteria"],"related":["psma-pet","ga68-psma-11","pylarify","prostate","prostate-bcr","prostate-mcrpc","psma-pet-to-rlt","eanm","snmmi","jeremie-calais","f-18","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2022,"doi":"10.2967/jnumed.121.263262","pmid":"34531258","authors":"Jadvar H, Calais J, Fanti S, Feng F, Greene KL, et al.","paperType":"guideline","findings":["PSMA PET rated appropriate (score 8) for staging newly diagnosed unfavourable-intermediate, high- or very-high-risk prostate cancer.","PSMA PET rated appropriate (score 9) for PSA rise after prostatectomy or radiotherapy (biochemical recurrence) and for confirming eligibility for PSMA-targeted radioligand therapy.","PSMA PET rated rarely appropriate (score 2-3) for detecting intraprostatic tumour in men with suspected but unbiopsied cancer, and for very low/low/favourable-intermediate-risk disease.","Panel included representatives from SNMMI, American College of Nuclear Medicine, American College of Physicians, ASCO, American Urological Association, ANZSNM and EANM."],"whatItMeans":"This guideline tells doctors and insurers exactly which clinical situations justify a PSMA PET scan for prostate cancer - mainly staging higher-risk disease, investigating a PSA rise after treatment, and checking that a patient's cancer will respond to PSMA radioligand therapy - and which situations do not.","caveats":["Appropriate use criteria reflect expert consensus and the evidence available in 2022; they are updated periodically and score some scenarios only as 'may be appropriate', reflecting genuine uncertainty rather than a firm answer.","Scores were assigned per clinical scenario, not per specific PSMA tracer; the panel treated different PSMA PET agents as broadly equivalent."],"changedPractice":true},{"id":"paper-cabinet-cabozantinib-nejm-2024","kind":"paper","name":"CABINET (Alliance A021602): cabozantinib for advanced neuroendocrine tumours","aka":[],"tldr":"Cabozantinib delayed progression in previously treated advanced neuroendocrine tumours of both pancreatic and extra-pancreatic origin compared with placebo, adding a new option after somatostatin analogues, everolimus or radioligand therapy.","summary":"Two parallel phase 3 placebo-controlled trials of cabozantinib in 298 patients with progressive advanced neuroendocrine tumours: 203 with extra-pancreatic (including lung and small bowel) and 95 with pancreatic tumours, all previously treated.\n\nMedian progression-free survival was 8.4 versus 3.9 months in extra-pancreatic tumours (hazard ratio 0.38) and 13.8 versus 4.4 months in pancreatic tumours (hazard ratio 0.23); hypertension, fatigue and diarrhoea were common.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2403991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282913/"}],"tags":[],"related":[],"indications":["lung-net","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cabinet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2403991","pmid":"39282913","authors":"Chan JA, Geyer S, Zemla T, et al.","paperType":"rct","findings":["Extra-pancreatic: median progression-free survival 8.4 vs 3.9 months; hazard ratio 0.38.","Pancreatic: 13.8 vs 4.4 months; hazard ratio 0.23."],"whatItMeans":"Cabozantinib is approved for previously treated neuroendocrine tumours of any origin and is a standard later-line choice, including for lung carcinoids.","caveats":["Trials stopped early at interim analysis; overall survival not powered.","Dose reductions needed in most patients."],"changedPractice":true,"participants":298},{"id":"paper-clarinet-lanreotide-nejm-2014","kind":"paper","name":"CLARINET: lanreotide in metastatic enteropancreatic neuroendocrine tumours","aka":[],"tldr":"The long-acting somatostatin analogue lanreotide roughly halved the risk of progression in non-functioning gut and pancreatic neuroendocrine tumours, extending the use of these drugs from symptom control to slowing tumour growth.","summary":"Phase 3 placebo-controlled trial of 204 patients with advanced, well- or moderately differentiated, non-functioning, somatostatin receptor-positive enteropancreatic neuroendocrine tumours (Ki-67 under 10 percent) randomised to lanreotide autogel 120 mg monthly or placebo.\n\nMedian progression-free survival was not reached with lanreotide against 18.0 months with placebo (hazard ratio 0.47), with benefit in pancreatic and midgut tumours and in patients with high hepatic tumour load.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1316158"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25014687/"}],"tags":[],"related":[],"indications":["pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1316158","pmid":"25014687","authors":"Caplin ME, Pavel M, Ćwikła JB, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.47.","24-month progression-free survival 65.1 percent vs 33.0 percent."],"whatItMeans":"Somatostatin analogues are the standard first-line antiproliferative treatment for grade 1 to 2 gastroenteropancreatic neuroendocrine tumours whether or not they cause a hormone syndrome.","caveats":["Most patients had stable disease at entry, so the natural history was slow.","No overall survival benefit shown."],"changedPractice":true,"participants":204},{"id":"paper-detect-a-science-2020","kind":"paper","name":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms","aka":[],"tldr":"The first prospective interventional study of a multi-analyte blood test (CancerSEEK) in asymptomatic people: 26 cancers were first detected by the blood test, most of them localised, and the test roughly doubled the number of cancers caught by standard screening.","summary":"DETECT-A enrolled 10,006 women aged 65-75 with no history of cancer in the Geisinger health system. A blood test measuring mutations in cell-free DNA and protein markers (CancerSEEK) was performed; a confirmed positive led to whole-body PET-CT, and imaging-positive participants were referred for diagnosis.\n\nTwenty-six cancers were detected by the blood test, of which 17 were localised or regional and 12 were treated with surgery with intent to cure. Standard-of-care screening detected a further 24 cancers, so combining the blood test with existing screening roughly doubled detection (from about a quarter to about half of incident cancers). Fewer than 1% of participants had an unnecessary invasive procedure.\n\nIt proved that a blood-first screening pathway can be safely operationalised and that many blood-detected cancers are at a curable stage.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.abb9601"},{"label":"ClinicalTrials.gov NCT03934866","url":"https://clinicaltrials.gov/study/NCT03934866"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2020,"doi":"10.1126/science.abb9601","pmid":"32345712","authors":"Lennon AM, Buchanan AH, Kinde I, et al.","paperType":"observational","findings":["Blood test alone detected 26 of 96 incident cancers (about 27% sensitivity); with standard screening the combined sensitivity was about 52%","17 of 26 blood-detected cancers were localised or regional; 12 patients had surgery with curative intent","The blood test found cancers in organs with no standard screening (ovary, kidney, appendix, uterus, lymphoma)","Participants did not reduce their uptake of standard screening after joining the study"],"whatItMeans":"A blood test can find early, treatable cancers in people who feel well, including cancers for which no screening exists. It is not a replacement for mammography or colonoscopy but a possible addition. Larger randomised trials are needed to show benefit outweighs harm.","caveats":["Single-arm, single health system, women only; no mortality endpoint","Sensitivity of about a quarter for all incident cancers means most cancers were missed","PET-CT confirmation for all positives is costly and exposes participants to radiation","CancerSEEK's commercial successor tests differ in design, so performance does not transfer directly"],"changedPractice":false,"participants":10006},{"id":"paper-eanm-lu177-dosimetry-recommendations-ejnmmi-2022","kind":"paper","name":"EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands","aka":[],"tldr":"European nuclear medicine physicists set out a detailed, agreed method for measuring exactly how much radiation dose a patient's kidneys and tumours actually receive during lutetium-177 treatments, so that dosing can eventually be tailored to the individual rather than fixed for everyone.","summary":"This EANM Dosimetry Committee document provides detailed, practical recommendations for performing patient-specific dosimetry during therapy with 177Lu-labelled somatostatin-receptor ligands (for neuroendocrine tumours) and 177Lu-PSMA ligands (for prostate cancer). It specifies imaging protocols (typically three well-separated SPECT/CT time points per cycle for kidney and tumour dosimetry), segmentation and recovery-correction methods, and reports the underlying pharmacokinetic and dosimetric literature: mean kidney absorbed doses of roughly 0.54-1.00 Gy/GBq for 177Lu-somatostatin-receptor ligands and 0.4-0.8 Gy/GBq for 177Lu-PSMA, and tumour absorbed doses typically 1-8 Gy/GBq, with inter-patient variability up to ninefold for 177Lu-PSMA.\n\nThe guideline notes that because 177Lu-PSMA-617 (Pluvicto) is approved for use at a fixed activity per cycle (7.4 GBq every 6 weeks), patient-specific dosimetry is not mandatory for on-label use, but the committee encourages its practice to build the evidence base for eventually personalising dose - an approach already used for decades in dosimetry-led PRRT centres.\n\nThis document, alongside the companion joint EANM/SNMMI 177Lu-PSMA-RLT procedure guideline, is the reference clinical physicists and nuclear medicine physicians use to standardise dosimetry methodology across centres, a prerequisite for any future trial of dosimetry-personalised versus fixed-activity radioligand therapy.","asOf":"2026-09-22","links":[{"label":"EANM: dosimetry guidelines overview","url":"https://eanm.org/publications/guidelines/overview/dosimetry/"},{"label":"PMC: full text","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9015994/"}],"tags":["guideline","dosimetry","lutetium-177"],"related":["radioligand-dosimetry","dosimetry","prrt","lu177-radioligand-therapy","pluvicto","eanm","gray-unit","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2022,"doi":"10.1007/s00259-022-05727-7","pmid":"35284969","authors":"Sjögreen Gleisner K, Chouin N, Gabina PM, Cicone F, Gnesin S, et al.","paperType":"guideline","findings":["Recommends kidney dosimetry using SPECT/CT at three well-separated time points between day 1 and day 7 after each therapy cycle.","Reports mean absorbed kidney doses of roughly 0.54-1.00 Gy/GBq for 177Lu-somatostatin-receptor ligands and 0.4-0.8 Gy/GBq for 177Lu-PSMA.","Reports mean tumour absorbed doses of approximately 1-8 Gy/GBq, with up to ninefold inter-patient variability for 177Lu-PSMA (range 0.09-0.84 Gy/GBq in one cited series).","Notes that patient-specific dosimetry is not mandatory for on-label 177Lu-PSMA-617 use, since it is approved at a fixed per-cycle activity."],"whatItMeans":"This document standardises how hospitals measure the actual radiation dose reaching a patient's kidneys and tumours during lutetium-177 treatment, laying the groundwork for shifting from a one-dose-fits-all schedule to treatment doses tailored to each patient's biology.","caveats":["Journal metadata note: the article was published in the European Journal of Nuclear Medicine and Molecular Imaging (2022;49(6):1778-1809); recorded here under Journal of Nuclear Medicine as the nearest catalogued match, so the DOI and PMID should be treated as authoritative for sourcing.","Recommendations are methodological guidance, not a mandate; dosimetry uptake still varies widely between centres and countries.","Absorbed-dose ranges cited are drawn from the pooled literature the committee reviewed, not from a single new dataset."],"changedPractice":true},{"id":"paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","kind":"paper","name":"Efficacy and safety of high-specific-activity 131I-MIBG therapy in advanced pheochromocytoma or paraganglioma","aka":[],"tldr":"A purified radioactive form of MIBG, taken up by adrenaline-producing tumour cells, let a quarter of patients halve their blood pressure medication for at least six months and shrank tumours in about one in five, leading to the first approved radiopharmaceutical for these tumours.","summary":"Open-label single-arm multicentre phase 2 study of high-specific-activity iobenguane I-131 in patients with MIBG-avid unresectable or metastatic pheochromocytoma or paraganglioma, given as up to two therapeutic doses; 68 patients received at least one dose.\n\nAbout a quarter of patients achieved the primary endpoint of at least a 50 percent reduction in antihypertensive medication for six months or more, objective responses occurred in about 22 percent, and most patients had disease control; myelosuppression was the main toxicity. The FDA approved the product (Azedra) in 2018.","asOf":"2026-09-18","links":[{"label":"J Nucl Med 2019","url":"https://doi.org/10.2967/jnumed.118.217463"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30291194/"}],"tags":[],"related":["i-131"],"indications":["metastatic-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.118.217463","pmid":"30291194","authors":"Pryma DA, Chin BB, Noto RB, et al.","paperType":"observational","findings":["At least a 50 percent reduction in antihypertensive medication for six months or longer in about a quarter of patients.","Objective tumour response in about 22 percent; myelosuppression was the main adverse effect."],"whatItMeans":"Radionuclide therapy is a standard option for MIBG-avid metastatic pheochromocytoma and paraganglioma; somatostatin receptor targeted lutetium therapy is the alternative for SSTR-avid disease.","caveats":["Single-arm study with a blood pressure medication endpoint rather than survival.","The commercial product was later withdrawn from the US market for business reasons, limiting access."],"changedPractice":true,"participants":68},{"id":"paper-strosberg-netter1-qol-jco-2018","kind":"paper","name":"Health-related quality of life in the NETTER-1 trial of 177Lu-Dotatate","aka":[],"tldr":"In people with a slow-growing gut cancer, the radioactive treatment lutetium-177 dotatate did not just shrink tumours for longer - it also kept their day-to-day quality of life, including energy, pain and diarrhoea, better for much longer than the older drug it was compared with.","summary":"This is the health-related quality-of-life (HRQoL) analysis of NETTER-1, the phase 3 trial that established 177Lu-Dotatate (Lutathera) for progressive midgut neuroendocrine tumours. Patients (117 on 177Lu-Dotatate, 114 on high-dose octreotide) completed the EORTC QLQ-C30 and GI.NET-21 questionnaires at baseline and every 12 weeks. Time to deterioration (TTD), defined as a fall of 10 points or more from baseline in a domain, was compared between arms by intention to treat.\n\nTTD was significantly longer with 177Lu-Dotatate across every domain tested: global health status (HR 0.406), physical functioning (HR 0.518), role functioning (HR 0.580), fatigue (HR 0.621), pain (HR 0.566), diarrhoea (HR 0.473), disease-related worries (HR 0.572) and body image (HR 0.425). The difference in median TTD was large in absolute terms - 28.8 months versus 6.1 months for global health status, and 25.2 versus 11.5 months for physical functioning.\n\nBecause NETTER-1's primary endpoint (progression-free survival) had already shown a large benefit, this paper mattered for showing the benefit was not bought at the cost of how patients felt day to day - in every domain measured, 177Lu-Dotatate patients did the same or better than those on high-dose octreotide, never worse. It is frequently cited alongside the primary NETTER-1 report to support PRRT's tolerability case to patients and payers.","asOf":"2026-09-22","links":[{"label":"PubMed: NETTER-1 quality-of-life analysis (JCO 2018)","url":"https://pubmed.ncbi.nlm.nih.gov/29878866/"},{"label":"ASCO Publications: full text","url":"https://ascopubs.org/doi/10.1200/JCO.2018.78.5865"}],"tags":["neuroendocrine tumours","PRRT","quality of life"],"related":["netter-1","paper-netter-1-nejm-2017","lutathera","prrt","small-intestinal-net","jonathan-strosberg","richard-baum","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO","year":2018,"doi":"10.1200/JCO.2018.78.5865","pmid":"29878866","authors":"Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, et al.","paperType":"rct","findings":["Time to QoL deterioration (10-point fall) was significantly longer with 177Lu-Dotatate than high-dose octreotide across all measured domains.","Global health status: median TTD 28.8 months (177Lu-Dotatate) vs 6.1 months (octreotide); HR 0.406, p<0.001.","Physical functioning: median TTD 25.2 vs 11.5 months; HR 0.518.","Diarrhoea (HR 0.473), fatigue (HR 0.621) and pain (HR 0.566) all deteriorated significantly later on 177Lu-Dotatate."],"whatItMeans":"People treated with the radioactive drug lutetium-177 dotatate kept feeling well for much longer - years rather than months, in several measures - than people on the standard high-dose hormone injection, on top of the tumour-control benefit already shown.","caveats":["Quality-of-life data are patient-reported and unblinded (the trial was open-label), which can bias favourable results toward the novel treatment.","Questionnaires were completed only until disease progression, so long-term quality of life beyond that point is not captured here.","This is a secondary/exploratory endpoint analysis of NETTER-1, not an independently powered trial."],"changedPractice":true,"participants":231},{"id":"paper-hofman-lupsma-lancet-oncol-2018","kind":"paper","name":"LuPSMA trial: single-arm phase 2 study of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer","aka":[],"tldr":"In an early single-hospital study, most men with advanced prostate cancer who had run out of standard treatments saw their PSA fall by at least half after being treated with the radioactive drug lutetium-177 PSMA-617, with mild side effects.","summary":"Conducted at Peter MacCallum Cancer Centre, Melbourne, this single-arm, single-centre phase 2 trial treated men with metastatic castration-resistant prostate cancer who had progressed after taxane chemotherapy and second-generation anti-androgens. Screening 68Ga-PSMA-11 and FDG PET/CT confirmed high PSMA expression before treatment; eligible men received up to four cycles of 177Lu-PSMA-617 (mean 7.5 GBq per cycle) six weeks apart. Endpoints were PSA response (≥50% decline), imaging response, toxicity and quality of life.\n\nOf 43 men screened, 30 were treated. Seventeen of 30 (57%, 95% CI 37-75) had a PSA decline of 50% or more. Objective response in nodal or visceral disease was seen in 14 of 17 (82%) evaluable patients. Toxicity was mostly low grade (dry mouth in 87%, transient nausea and fatigue in 50%), though grade 3-4 thrombocytopenia occurred in 13%. Clinically meaningful pain and global-health-score improvements were recorded from the second cycle onward in over a third of patients.\n\nThis was one of the pivotal early single-arm studies (alongside German centres' compassionate-use experience) that generated the response-rate and toxicity signal used to justify the subsequent randomised trials TheraP and VISION, and it is one of the most-cited early efficacy reports for PSMA radioligand therapy.","asOf":"2026-09-22","links":[{"label":"PubMed: LuPSMA trial (Lancet Oncol 2018)","url":"https://pubmed.ncbi.nlm.nih.gov/29752180/"}],"tags":["prostate cancer","radioligand therapy","phase 2"],"related":["therap","vision","lu177-radioligand-therapy","psma-pet","prostate-mcrpc","hofman-michael","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30198-0","pmid":"29752180","authors":"Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, et al.","paperType":"observational","findings":["17 of 30 patients (57%, 95% CI 37-75) achieved a PSA decline of 50% or more.","Objective response in nodal or visceral disease in 14 of 17 (82%) evaluable patients.","Grade 1 dry mouth in 87%, grade 1-2 nausea and fatigue each in 50%; grade 3-4 thrombocytopenia in 13% (4 of 30).","37% of patients had a 10-point or greater improvement in global health score by the second treatment cycle; no treatment-related deaths."],"whatItMeans":"In a small early trial, most heavily pre-treated men with advanced prostate cancer responded to the PSMA-targeted radioactive drug, with manageable side effects, supporting the case for testing it in larger randomised trials.","caveats":["Single-arm, single-centre design with no comparator - response rates cannot be attributed to the drug alone with the same confidence as a randomised trial.","Small sample size (30 treated patients) limits precision of toxicity estimates, particularly for rarer serious events.","Patients were required to have high PSMA expression on screening PET, so results do not apply to PSMA-low disease."],"changedPractice":true,"participants":30},{"id":"paper-netter-1-nejm-2017","kind":"paper","name":"NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide","aka":[],"tldr":"Radioligand therapy with lutetium-177 dotatate reduced the risk of progression or death by nearly 80 percent compared with high-dose octreotide in midgut neuroendocrine tumours, the first randomised proof that targeted radiation works in these cancers.","summary":"Phase 3 trial of 229 patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumours randomised to four cycles of 177Lu-Dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR 60 mg.\n\nProgression-free survival at 20 months was 65.2 versus 10.8 percent (hazard ratio 0.21), response 18 versus 3 percent, and an interim analysis suggested improved overall survival; myelosuppression was modest.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1607427"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28076709/"}],"tags":[],"related":["lu-177"],"indications":["small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1607427","pmid":"28076709","authors":"Strosberg J, El-Haddad G, Wolin E, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.21; 20-month rate 65.2 percent vs 10.8 percent.","Objective response 18 percent vs 3 percent."],"whatItMeans":"Lutetium-177 dotatate is a standard treatment for progressive small bowel neuroendocrine tumours after somatostatin analogues, and NETTER-2 has since moved it into first-line use for higher-grade tumours.","caveats":["Final overall survival difference (48.0 vs 36.3 months) did not reach significance, partly because of crossover.","Rare late myelodysplasia and leukaemia."],"changedPractice":true,"participants":229},{"id":"paper-netter-2-lancet-2024","kind":"paper","name":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","aka":[],"tldr":"Using the radioactive drug lutetium dotatate as the first treatment for faster-growing neuroendocrine tumours, rather than saving it for later, nearly tripled the time without progression compared with high-dose octreotide.","summary":"Open-label phase 3 trial of 226 patients with newly diagnosed, somatostatin-receptor-positive grade 2-3 (Ki-67 10-55%) advanced gastroenteropancreatic neuroendocrine tumours randomised 2:1 to four cycles of 177Lu-dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR (60 mg). Primary endpoint was PFS by blinded review.\n\nMedian PFS was 22.8 vs 8.5 months (HR 0.28) with an objective response rate of 43% vs 9%. Following NETTER-1 (which established lutetium dotatate in progressive midgut tumours), it moved radioligand therapy to the first line for higher-grade disease, where somatostatin analogues alone are weak.","asOf":"2026-09-08","links":[{"label":"PubMed search: NETTER-2 Lancet 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"},{"label":"ClinicalTrials.gov NCT03972488","url":"https://clinicaltrials.gov/study/NCT03972488"}],"tags":[],"related":["lu-177"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","dosimetry"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00701-3","pmid":"38851203","authors":"Singh S, Halperin D, Myrehaug S, et al.","paperType":"rct","findings":["Median PFS 22.8 vs 8.5 months; HR 0.28 (95% CI 0.18-0.42).","Objective response 43.0% vs 9.3%.","Benefit consistent in grade 2 and grade 3 tumours and in pancreatic and small-bowel primaries.","Grade 3 or higher adverse events about 35% vs 28%; no cases of treatment-related myelodysplasia or leukaemia at the primary analysis.","Overall survival data immature; crossover to lutetium dotatate was permitted at progression."],"whatItMeans":"Patients newly diagnosed with an advanced grade 2 or 3 neuroendocrine tumour of the gut or pancreas that shows somatostatin receptors on imaging can now receive lutetium dotatate as their first treatment, gaining more than a year of additional disease control and a much higher chance of tumour shrinkage. It does not settle whether radioligand therapy is better than other first-line options such as capecitabine-temozolomide or everolimus, and long-term marrow safety with earlier use needs surveillance.","caveats":["Comparator was high-dose octreotide, which has limited anti-proliferative activity in grade 2-3 tumours.","Overall survival not yet shown; crossover will make it hard to demonstrate.","Long-term risks of earlier radioligand exposure (marrow, kidney, secondary leukaemia) require follow-up.","Requires somatostatin-receptor PET and nuclear medicine capacity; grade 3 tumours with Ki-67 above 55% were excluded."],"changedPractice":true,"participants":226},{"id":"paper-tagawa-ac225-j591-jco-2024","kind":"paper","name":"Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC","aka":[],"tldr":"The first human test of an alpha-emitting radioactive drug attached to an antibody (rather than a small molecule) against PSMA found a safe dose in men with advanced prostate cancer who had exhausted other treatments, and shrank the PSA marker in nearly half of them - including those whose cancer had already stopped responding to the more common lutetium-177 PSMA treatment.","summary":"This first-in-human phase 1 dose-escalation trial tested 225Ac-J591 - the anti-PSMA monoclonal antibody J591 labelled with the alpha emitter actinium-225 - as a single intravenous dose in 32 men with progressive metastatic castration-resistant prostate cancer who had received or were ineligible for taxane chemotherapy and an androgen receptor pathway inhibitor. Unlike PSMA-617 or PSMA-I&T, J591 is a full antibody rather than a small peptidomimetic ligand, giving different pharmacokinetics (slower clearance, longer tumour residence). Patients were treated across seven dose levels (13.3 to 93.3 kBq/kg) without pre-selection by PSMA PET.\n\nOne dose-limiting toxicity (grade 4 anaemia and thrombocytopenia) occurred at 80 kBq/kg; none occurred at the highest dose level tested (93.3 kBq/kg), so a maximum tolerated dose was not reached and the recommended phase 2 dose was set at the top studied level. Most high-grade adverse events were haematological and dose-related; non-haematological toxicity was generally low grade - a different pattern from PSMA-617-based alpha agents, where xerostomia (dry mouth) from salivary gland uptake dominates, since antibodies clear the salivary glands less than small-molecule ligands. Efficacy signals were encouraging for a phase 1, dose-finding, unselected population: 46.9% of patients had a PSA decline of 50% or more at some point, 34.4% had a confirmed PSA50 response, and 59.1% had control of circulating tumour cells, with responses seen regardless of prior 177Lu-PSMA exposure.\n\nAs one of the first published clinical results for an antibody-based (rather than small-molecule) PSMA alpha-emitter, this trial supports antibody-delivered alpha therapy as a second route to targeted alpha therapy in prostate cancer, potentially with a different toxicity trade-off (more marrow suppression, less xerostomia) than PSMA-617-based agents, and without requiring PSMA PET pre-selection.","asOf":"2026-09-22","links":[{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/37922438/"},{"label":"ASCO Publications: full text","url":"https://ascopubs.org/doi/10.1200/JCO.23.00573"}],"tags":["alpha therapy","prostate cancer","phase 1"],"related":["ac225-psma","targeted-alpha-therapy","psma","prostate-mcrpc","oliver-sartor","beta-then-alpha","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO","year":2024,"doi":"10.1200/JCO.23.00573","pmid":"37922438","authors":"Tagawa ST, Thomas C, Sartor AO, Sun M, Stangl-Kremser J, et al.","paperType":"rct","findings":["Recommended phase 2 dose was the highest studied level, 93.3 kBq/kg; maximum tolerated dose was not reached across seven dose levels.","One dose-limiting toxicity (grade 4 anaemia and thrombocytopenia) occurred, at 80 kBq/kg; none at the highest dose level.","46.9% of patients had a PSA decline of 50% or more at any time; 34.4% had a confirmed PSA50 response.","Circulating tumour cell count control occurred in 13 of 22 evaluable patients (59.1%); responses were seen regardless of prior 177Lu-PSMA treatment.","High-grade adverse events were predominantly haematological and radioactivity-dose related; non-haematological toxicity was generally low grade."],"whatItMeans":"An alpha-emitting radioactive drug built on a PSMA-targeting antibody, rather than the small-molecule ligands used in existing PSMA therapies, was safe enough to move into further testing and shrank PSA in roughly a third to a half of heavily pre-treated men, including some whose cancer had already stopped responding to lutetium-177 PSMA therapy.","caveats":["Small, single-arm, phase 1 dose-escalation trial (32 patients) - not designed or powered to show a survival or definitive efficacy benefit.","No PSMA PET pre-selection was used, unlike VISION and TheraP, so response rates are not directly comparable to those trials.","Blood toxicity (anaemia, thrombocytopenia) tracked with dose, which will need careful management as the drug moves into larger trials."],"changedPractice":false,"participants":32},{"id":"paper-propsma-hofman-lancet-2020","kind":"paper","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","aka":[],"tldr":"PSMA PET-CT was 27 percentage points more accurate than CT and bone scan for finding spread in men with high-risk prostate cancer before treatment, with less radiation and more influence on management, and it has replaced conventional imaging where available.","summary":"Randomised multicentre trial of 302 men with high-risk localised prostate cancer randomised to conventional imaging (CT and bone scan) or gallium-68 PSMA PET-CT for staging, with crossover imaging to define a reference standard.\n\nAccuracy was 92 percent for PSMA PET-CT against 65 percent for conventional imaging, with higher sensitivity (85 versus 38 percent) and specificity, fewer equivocal results, lower radiation dose and more frequent management change.","asOf":"2026-09-17","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(20)30314-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32209449/"}],"tags":[],"related":["ga-68"],"indications":["prostate-bcr","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["propsma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7","pmid":"32209449","authors":"Hofman MS, Lawrentschuk N, Francis RJ, et al.","paperType":"rct","findings":["Accuracy 92 percent vs 65 percent (27 percent absolute difference).","Sensitivity 85 percent vs 38 percent; specificity 98 percent vs 91 percent."],"whatItMeans":"PSMA PET-CT is the preferred staging investigation for high-risk prostate cancer and for biochemical recurrence, though most treatment trials were designed with conventional imaging.","caveats":["Reference standard relied partly on imaging follow-up rather than histology.","Detecting more disease does not by itself prove better outcomes."],"changedPractice":true,"participants":302},{"id":"paper-psmafore-lancet-2024","kind":"paper","name":"PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC","aka":[],"tldr":"In men with advanced prostate cancer who had not yet had chemotherapy but whose disease had grown on one hormone-blocking drug, switching to the radioactive PSMA treatment kept the cancer under control for longer than switching to a different hormone drug.","summary":"PSMAfore was a phase 3, randomised, controlled, open-label trial at 74 sites in Europe and North America. Taxane-naive men with PSMA-positive metastatic castration-resistant prostate cancer who had progressed once on an androgen receptor pathway inhibitor (ARPI) were randomised 1:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for six cycles) or a change of ARPI (abiraterone or enzalutamide). Crossover to 177Lu-PSMA-617 was permitted after confirmed radiographic progression on ARPI change. The primary endpoint was radiographic progression-free survival (rPFS).\n\nOf 468 randomised men, updated analysis (median follow-up ~24 months) showed median rPFS of 11.6 months with 177Lu-PSMA-617 versus 5.6 months with ARPI change (HR 0.49, 95% CI 0.39-0.61). The final overall survival analysis (Ann Oncol 2025) found no significant intention-to-treat difference (24.5 vs 23.1 months, HR 0.91, p=0.20), heavily confounded by a 60% crossover rate from the control arm; a crossover-adjusted analysis suggested benefit (HR 0.59). Grade 3+ and serious adverse events were less frequent with 177Lu-PSMA-617 than with ARPI change.\n\nPSMAfore moved PSMA radioligand therapy earlier in the treatment sequence - before chemotherapy - and was the evidentiary basis, alongside VISION, for regulators to consider extending 177Lu-PSMA-617 use to the pre-taxane setting.","asOf":"2026-09-22","links":[{"label":"PubMed: PSMAfore primary results (Lancet 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39293462/"},{"label":"PubMed: PSMAfore final overall survival (Ann Oncol 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/40680993/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["psmafore","vision","pluvicto","psma-pet","prostate-mcrpc","arpi","michael-morris","ken-herrmann","oliver-sartor","karim-fizazi","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01653-2","pmid":"39293462","authors":"Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, et al.","paperType":"rct","findings":["Updated analysis: median rPFS 11.6 months (177Lu-PSMA-617) vs 5.6 months (ARPI change); HR 0.49 (95% CI 0.39-0.61).","Primary analysis: median rPFS 9.3 months vs 5.55 months; HR 0.41 (95% CI 0.29-0.56), p<0.0001.","Final overall survival (intention to treat): 24.48 vs 23.13 months, HR 0.91 (95% CI 0.72-1.14), p=0.20; crossover-adjusted HR 0.59 (95% CI 0.38-0.91).","60.3% of men assigned to ARPI change crossed over to 177Lu-PSMA-617 after progression.","Grade 3+ treatment-emergent adverse events: 60.8 per 100 patient-treatment years (177Lu-PSMA-617) vs 85.1 (ARPI change)."],"whatItMeans":"For men who still have a working hormone treatment option but whose cancer is progressing, offering the PSMA radioligand therapy sooner - before chemotherapy - delayed disease progression, though it did not clearly extend how long men lived once the very high rate of patients switching over is accounted for.","caveats":["Open-label design and high crossover from control to experimental arm make the overall-survival comparison unreliable by intention to treat.","Crossover-adjusted survival analyses rely on modelling assumptions rather than randomisation.","Trial excluded men who had already had a taxane, so results do not generalise to post-chemotherapy patients (that population is VISION and TheraP)."],"changedPractice":true,"participants":468},{"id":"paper-sgouros-tat-review-nat-rev-2020","kind":"paper","name":"Radiopharmaceutical therapy in cancer: clinical advances and challenges","aka":[],"tldr":"A review, written for drug developers, of how radioactive cancer drugs work, which ones had reached patients by 2020, and what stands in the way of making more of them.","summary":"This review by Sgouros, Bodei, McDevitt and Nedrow surveys the state of radiopharmaceutical therapy (RPT) as of 2020: the physics of alpha, beta and Auger emitters, the targeting chemistry (small molecules, peptides, antibodies), the theranostic pairing of imaging and therapy isotopes, and the clinical evidence behind approved and late-stage agents (iodine-131, radium-223, lutetium-177 dotatate, and the then-emerging lutetium-177 and actinium-225 PSMA agents). It frames RPT's central advantage - imageable biodistribution paired with cytotoxic effect, and a favourable toxicity profile relative to most systemic cytotoxic therapies - and its central bottlenecks: isotope supply, dosimetry standardisation, and the absence of a companion-diagnostic regulatory pathway equivalent to that for drugs.\n\nThe review does not report new clinical data; its contribution is a structured account of the field's trajectory and the translational problems (manufacturing scale, radiobiology of low dose-rate irradiation, patient selection biomarkers) that a decade of subsequent approvals (Pluvicto, Lutathera label expansions) had to solve.\n\nIt is widely cited as a field-level reference in subsequent radiopharmaceutical papers and grant applications, alongside the companion 2020 Lancet Oncology roadmap by Herrmann and colleagues.","asOf":"2026-09-22","links":[{"label":"Nature Reviews Drug Discovery: full text","url":"https://www.nature.com/articles/s41573-020-0073-9"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/32728207/"}],"tags":["review","radiopharmaceutical therapy"],"related":["targeted-alpha-therapy","radioligand-therapy","therapy-isotope-supply-chain","radioligand-dosimetry","theranostics","lu-177","ac-225","ra-223","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2020,"doi":"10.1038/s41573-020-0073-9","pmid":"32728207","authors":"Sgouros G, Bodei L, McDevitt MR, Nedrow JR","paperType":"review","findings":["Surveys approved and late-stage radiopharmaceutical therapies as of 2020 (iodine-131, radium-223, 177Lu-dotatate, emerging PSMA agents) and their radiobiological basis.","Identifies isotope supply, standardised dosimetry, and regulatory pathways for companion imaging diagnostics as the principal translational bottlenecks for the field.","Frames radiopharmaceutical therapy's comparative advantage as imageable biodistribution combined with generally lower toxicity than systemic cytotoxic chemotherapy."],"whatItMeans":"This paper is a map of the radioactive-cancer-drug field at a pivotal moment, explaining to non-specialists and drug developers alike why these treatments work differently from chemotherapy and what needed to be fixed - supply, dosing science, regulation - before more of them could reach patients.","caveats":["As a narrative review, it synthesises published data rather than presenting new trial results, and reflects the evidence base and pipeline as they stood in 2020.","Note the journal is Nature Reviews Drug Discovery (the corpus records this under the closest matching journal entry, Nature Medicine, as Nature Reviews Drug Discovery is not separately catalogued); consult the DOI/PMID for the exact source."],"changedPractice":false},{"id":"paper-herrmann-radiotheranostics-lancet-oncol-2020","kind":"paper","name":"Radiotheranostics: a roadmap for future development","aka":[],"tldr":"A group of leading nuclear medicine specialists set out, in one article, what needs to happen - in science, manufacturing, regulation and training - for more radioactive scan-and-treat drugs to reach patients over the following five years.","summary":"This roadmap article, led by Ken Herrmann with co-authors including Jason Lewis, argues that radiotheranostics - radiopharmaceuticals that both image and treat the same molecular target - had reached an inflection point by 2020, with several agents already approved and many more in the pipeline. Rather than reporting new trial data, it lays out the practical barriers standing in the way of that pipeline reaching patients: logistics of a decaying drug (short shelf life, need for rapid distribution), isotope supply chains, the absence of harmonised regulatory frameworks for paired diagnostic-therapeutic products, reimbursement, and the shortage of trained nuclear medicine physicians and technologists.\n\nThe authors call for multidisciplinary clinical trial designs that pair imaging biomarker development with therapeutic dose-finding from the outset, rather than treating the diagnostic and therapeutic halves of a theranostic pair as separate regulatory programmes.\n\nPublished in the same year as the FDA approval of 177Lu-dotatate's expanded indications and shortly before the VISION trial results, it is frequently cited as a statement of the field's ambitions and obstacles just before radioligand therapy entered mainstream oncology practice with Pluvicto's 2022 approval.","asOf":"2026-09-22","links":[{"label":"The Lancet Oncology: article","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30821-6/abstract"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/32135118/"}],"tags":["review","roadmap","theranostics"],"related":["theranostics","therapy-isotope-supply-chain","radiopharmaceutical-gmp-release","radiopharmacy-network","ken-herrmann","jason-lewis","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(19)30821-6","pmid":"32135118","authors":"Herrmann K, Schwaiger M, Lewis JS, Solomon SB, McNeil BJ, et al.","paperType":"review","findings":["Identifies logistics of short-half-life radiopharmaceuticals, isotope supply, and fragmented regulatory pathways for paired diagnostic-therapeutic products as the main barriers to radiotheranostics reaching more patients.","Calls for trial designs that integrate imaging-biomarker qualification with therapeutic dose-finding rather than developing the diagnostic and therapeutic halves separately.","Flags workforce shortages in nuclear medicine training as a practical constraint on scaling radiotheranostics services."],"whatItMeans":"This article is a call to action from senior nuclear medicine physicians: the treatments were becoming ready, but hospitals, regulators and isotope suppliers were not yet organised to deliver them at scale - a warning that proved accurate when demand for lutetium-177 PSMA therapy outstripped supply after 2022.","caveats":["An expert roadmap and opinion piece, not a systematic review or trial report; recommendations reflect the authors' priorities rather than a formal consensus process.","Written before the VISION trial and Pluvicto's approval, so some of its forward-looking statements have since been superseded by events."],"changedPractice":false},{"id":"paper-rathl-interim-pet-adapted-abvd-advanced-hodgkin-nejm-2016","kind":"paper","name":"RATHL: adapted treatment guided by interim PET-CT in advanced Hodgkin lymphoma","aka":[],"tldr":"Using a PET scan after two cycles to decide the rest of treatment let patients with a clear scan drop bleomycin, sparing their lungs without losing cure, while those with a positive scan were escalated to stronger chemotherapy.","summary":"International randomised trial of 1,214 patients with advanced Hodgkin lymphoma who had an interim PET-CT after two cycles of ABVD; PET-negative patients were randomised to continue ABVD or switch to AVD (omitting bleomycin), and PET-positive patients were escalated to BEACOPP.\n\nThree-year progression-free survival was 85.7 percent with ABVD and 84.4 percent with AVD, with fewer pulmonary adverse events after bleomycin was dropped; PET-positive patients escalated to BEACOPP had a three-year progression-free survival of 67.5 percent, better than expected. PET-adapted therapy became standard.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1510093"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27332902/"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rathl"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1510093","pmid":"27332902","authors":"Johnson P, Federico M, Kirkwood A, et al.","paperType":"rct","findings":["Three-year progression-free survival 85.7 percent with continued ABVD versus 84.4 percent with AVD after a negative interim PET.","Fewer pulmonary and other toxic effects without bleomycin; PET-positive patients escalated to BEACOPP had 67.5 percent three-year progression-free survival."],"whatItMeans":"An interim PET scan after two cycles guides treatment of advanced Hodgkin lymphoma: drop bleomycin if negative, intensify if positive.","caveats":["The non-inferiority margin for AVD was not formally met in the intention-to-treat analysis, though the difference was small.","Predates brentuximab vedotin and nivolumab combinations, which now often replace ABVD."],"changedPractice":true,"participants":1214},{"id":"paper-baum-prrt-1048-patients-oncotarget-2018","kind":"paper","name":"Results and adverse events of personalised peptide receptor radionuclide therapy in 1048 patients with neuroendocrine neoplasms","aka":[],"tldr":"The largest single-centre report of a radioactive treatment for neuroendocrine tumours, from over a thousand patients treated across a decade at one German hospital, showing typical survival times and how often serious side effects such as blood cancers occurred.","summary":"This retrospective single-centre analysis from Zentralklinik Bad Berka, Germany, reports outcomes for 1048 patients with neuroendocrine neoplasms treated with personalised peptide receptor radionuclide therapy (PRRT) using 90Y- and/or 177Lu-labelled somatostatin analogues between 2004 and 2014, drawn from 2294 patients screened by 68Ga-SSTR PET/CT. Radionuclide, dose and cycle number were individualised to tumour and organ dosimetry rather than fixed, reflecting the Bad Berka group's long-standing personalised-dosimetry approach to PRRT, predating the fixed four-cycle regimen later used in NETTER-1.\n\nMedian overall survival across all patients was 51 months (95% CI 47.0-54.9), varying significantly by radionuclide used, tumour grade, prior therapies and tumour origin (for example, gastrinoma and glucagonoma patients had median survival of 66 and 127 months respectively; insulinoma patients 32 months). Median progression-free survival (by 68Ga-SSTR PET/CT with EORTC criteria) was 19 months. Myelodysplastic syndrome or leukaemia developed in 22 patients (2.1%), and five patients required haemodialysis after treatment; other serious adverse events were rare.\n\nAs one of the largest published PRRT cohorts, and predating the randomised NETTER-1 trial, this paper was widely cited as real-world evidence for PRRT's long-term safety and effectiveness, and its dosimetry-personalised approach is a touchstone for the ongoing debate about fixed-activity versus dosimetry-guided PRRT dosing.","asOf":"2026-09-22","links":[{"label":"PMC: full text","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5908296/"},{"label":"PubMed record","url":"https://pubmed.ncbi.nlm.nih.gov/29682217/"}],"tags":["neuroendocrine tumours","PRRT","real-world evidence"],"related":["prrt","lutathera","neuroendocrine","radioligand-dosimetry","richard-baum","paper-netter-1-nejm-2017","ga-68","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Oncotarget","year":2018,"doi":"10.18632/oncotarget.24524","pmid":"29682217","authors":"Baum RP, Kulkarni HR, Singh A, Kaemmerer D, Mueller D, et al.","paperType":"observational","findings":["Median overall survival across all 1048 patients: 51 months (95% CI 47.0-54.9), varying by radionuclide, tumour grade, prior therapies and site of origin.","Median progression-free survival by 68Ga-SSTR PET/CT: 19 months overall.","Myelodysplastic syndrome or leukaemia developed in 22 of 1048 patients (2.1%); 5 patients required haemodialysis after treatment.","Survival varied widely by tumour subtype: gastrinoma 66 months and glucagonoma 127 months median OS, versus insulinoma 32 months."],"whatItMeans":"In the largest reported group of neuroendocrine tumour patients treated with individually dosed radioactive peptide therapy, most people lived several years after treatment, and serious long-term harms such as blood cancers were uncommon but real, occurring in about 1 in 50 patients.","caveats":["Retrospective, single-centre, uncontrolled cohort - there is no comparator arm, so the survival figures cannot be attributed to PRRT alone.","Radionuclide choice, dose and cycle number were personalised per patient rather than fixed, so results may not generalise directly to fixed-activity regimens such as the one used in NETTER-1 or Lutathera's approved label.","Long recruitment period (2004-2014) spans changes in imaging, patient selection and supportive care that could affect outcomes over time."],"changedPractice":false,"participants":1048},{"id":"paper-sempet-de-santis-jco-2004","kind":"paper","name":"SEMPET: FDG-PET as a predictor of viable tumour in post-chemotherapy seminoma residuals","aka":[],"tldr":"A PET scan reliably told apart residual masses that still contained living seminoma from scar tissue after chemotherapy, allowing surgeons to leave PET-negative masses alone rather than operating on all masses over 3 cm.","summary":"Prospective multicentre study of 51 patients with metastatic seminoma and residual masses after chemotherapy who underwent FDG-PET, with results validated against histology or clinical follow-up.\n\nPET had a sensitivity of 80 percent and specificity of 100 percent for viable tumour, and for residual lesions over 3 cm specificity and sensitivity were both 100 percent, outperforming CT size criteria.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2004","url":"https://doi.org/10.1200/JCO.2004.07.188"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15020605/"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2004,"doi":"10.1200/JCO.2004.07.188","pmid":"15020605","authors":"De Santis M, Becherer A, Bokemeyer C, et al.","paperType":"observational","findings":["Specificity 100 percent, sensitivity 80 percent for viable residual seminoma.","Sensitivity and specificity 100 percent for lesions over 3 cm."],"whatItMeans":"FDG-PET is standard for residual seminoma masses larger than 3 cm after chemotherapy, sparing most men surgery.","caveats":["Small study; false positives occur when PET is done too soon after chemotherapy, so scans are delayed at least six weeks."],"changedPractice":true,"participants":51},{"id":"paper-therap-lancet-2021","kind":"paper","name":"TheraP: [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer","aka":[],"tldr":"In men whose prostate cancer had grown after chemotherapy, a radioactive drug that homes in on prostate cancer cells (lutetium-177 PSMA-617) shrank the PSA marker in more men, and caused fewer serious side effects, than the standard chemotherapy drug it was compared with.","summary":"TheraP (ANZUP 1603) was an open-label, randomised phase 2 trial at 11 Australian centres. Men with metastatic castration-resistant prostate cancer progressing after docetaxel, selected by centrally reviewed 68Ga-PSMA-11 and FDG PET/CT (excluding FDG-positive/PSMA-negative discordant disease), were randomised 1:1 to [177Lu]Lu-PSMA-617 (6.0-8.5 GBq IV every 6 weeks, up to six cycles) or cabazitaxel (20 mg/m2 IV every 3 weeks, up to ten cycles). The primary endpoint was a PSA50 response.\n\nOf 291 men screened, 200 were PET-eligible and randomised. PSA50 responses were 66% with 177Lu-PSMA-617 versus 37% with cabazitaxel by intention to treat (difference 29 percentage points, 95% CI 16-42, p<0.0001). Grade 3-4 adverse events were less frequent with the radioligand (33% versus 53%). A mature follow-up analysis (Hofman et al., Lancet Oncology 2024) found overall survival was similar between arms (restricted mean survival time 19.1 versus 19.6 months), with substantial crossover (32% of the radioligand-therapy group and 20% of the cabazitaxel group went on to the other treatment).\n\nTheraP was the first randomised trial to compare a PSMA radioligand head-to-head against a standard chemotherapy and used PET-based patient selection prospectively, a design later echoed by VISION and PSMAfore. It helped establish 177Lu-PSMA-617 (subsequently approved as Pluvicto) as a credible alternative to cabazitaxel in the post-docetaxel setting.","asOf":"2026-09-22","links":[{"label":"PubMed: TheraP primary results (Lancet 2021)","url":"https://pubmed.ncbi.nlm.nih.gov/33581798/"},{"label":"PubMed: TheraP overall survival (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/38043558/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["therap","vision","lu177-radioligand-therapy","pluvicto","psma-pet","cabazitaxel","prostate-mcrpc","michael-morris","hofman-michael","louise-emmett","sandhu-shahneen","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00237-3","pmid":"33581798","authors":"Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, et al.","paperType":"rct","findings":["PSA50 response: 66% (177Lu-PSMA-617) vs 37% (cabazitaxel) by intention to treat; difference 29% (95% CI 16-42), p<0.0001.","Grade 3-4 adverse events: 33% (98 men, PSMA arm) vs 53% (85 men, cabazitaxel arm); no deaths attributed to 177Lu-PSMA-617.","Mature follow-up (median 35.7 months): overall survival restricted mean survival time 19.1 months (PSMA) vs 19.6 months (cabazitaxel), difference -0.5 months (95% CI -3.7 to 2.7), p=0.77 - no evidence of an OS difference.","80 of 291 registered men (27%) were excluded after PET screening for low PSMA expression or FDG-discordant disease; their median survival was substantially shorter (RMST 11.0 months)."],"whatItMeans":"For men whose prostate cancer has grown after chemotherapy, a PSMA-targeted radioactive treatment worked at least as well as, and was gentler than, the chemotherapy drug it replaced - provided a PET scan first confirms the cancer takes up the PSMA tracer.","caveats":["Phase 2, single-country (Australia), open-label, not powered for overall survival as a primary endpoint.","High crossover between arms after the randomised period complicates the survival comparison.","PET-based selection excluded over a quarter of screened men, whose prognosis was worse regardless of treatment - the trial says nothing about that PSMA-negative group."],"changedPractice":true,"participants":200},{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","aka":[],"tldr":"A radioactive drug that homes to the PSMA protein on prostate cancer cells helped men with heavily pretreated metastatic prostate cancer live about four months longer, launching radioligand therapy as a mainstream treatment.","summary":"Open-label phase 3 trial of 831 men with PSMA-PET-positive metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor pathway inhibitor and one or two taxanes, randomised 2:1 to 177Lu-PSMA-617 (7.4 GBq every six weeks for up to six cycles) plus protocol-permitted standard care, or standard care alone. Primary endpoints were radiographic PFS and OS.\n\nMedian OS was 15.3 vs 11.3 months (HR 0.62) and median rPFS 8.7 vs 3.4 months (HR 0.40). It led to FDA and EMA approval of Pluvicto in 2022, the first radioligand therapy to show a survival benefit in a common cancer, and made PSMA PET a theranostic gatekeeper.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03511664","url":"https://clinicaltrials.gov/study/NCT03511664"}],"tags":[],"related":["psma-pet-to-rlt","lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","psma-pet","pet-ct"],"targets":["psma"],"drugs":["pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","alpha-vs-beta","dosimetry"],"trials":["vision","psmafore"],"people":["karim-fizazi","michael-morris"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2107322","authors":"Sartor O, de Bono J, Chi KN, et al.","paperType":"rct","findings":["Median overall survival 15.3 vs 11.3 months; HR 0.62 (95% CI 0.52-0.74).","Median radiographic PFS 8.7 vs 3.4 months; HR 0.40 (99.2% CI 0.29-0.57).","PSA decline of 50% or more in 46% vs 7%; objective response in measurable disease 30% vs 2%.","Grade 3 or higher adverse events 53% vs 38%, mainly anaemia, thrombocytopenia and fatigue; dry mouth was common but rarely severe.","About 13% of screened patients were excluded by PSMA PET (PSMA-negative lesions), and early dropout in the control arm required protocol changes."],"whatItMeans":"Men with metastatic castration-resistant prostate cancer that has progressed after hormonal therapy and chemotherapy, and whose tumours show PSMA on a PET scan, can now receive lutetium-PSMA, which extends life, controls pain and is usually better tolerated than further chemotherapy. It has established a new treatment class in which a scan decides who gets the matching radioactive drug, and it is now being tested earlier in the disease (PSMAfore, PSMAddition).","caveats":["Standard care in the control arm excluded chemotherapy, radium-223 and other active drugs, and about 56% of control patients withdrew early, weakening the comparison.","Open-label; the OS benefit is nonetheless robust to sensitivity analyses.","Requires nuclear medicine infrastructure, isotope supply and PSMA PET access, which are unequally distributed.","PSMAfore in the pre-chemotherapy setting improved rPFS but not OS, because most control patients crossed over."],"changedPractice":true,"participants":831},{"id":"paper-zircon-lancet-oncol-2024","kind":"paper","name":"ZIRCON: [89Zr]Zr-girentuximab PET-CT for detecting clear-cell renal cell carcinoma","aka":[],"tldr":"A PET scan using a radioactively-labelled antibody could tell, without surgery, whether a suspicious kidney lump was the most common type of kidney cancer - correctly in about 9 out of 10 people.","summary":"ZIRCON was a prospective, open-label, multicentre phase 3 trial at 36 sites in nine countries. Adults with an indeterminate renal mass of 7 cm or less (cT1), suspicious for clear-cell renal cell carcinoma (ccRCC) and scheduled for nephrectomy, received a single dose of [89Zr]Zr-girentuximab (37 MBq, 10 mg antibody) intravenously, followed by PET-CT 5 (±2) days later. Blinded central histopathological review of the surgical specimen was the reference standard. Co-primary endpoints were sensitivity and specificity for ccRCC detection.\n\nOf 332 enrolled patients, 300 received the tracer and 284 were evaluable in the primary analysis. Mean sensitivity was 85.5% (95% CI 81.5-89.6) and mean specificity was 87.0% (81.0-93.1) across three independent readers; positive predictive value was around 93%. The safety profile was favourable: most adverse events occurred peri-operatively and were unrelated to the tracer, with no treatment-related deaths.\n\n[89Zr]Zr-girentuximab (TLX250-CDx, Telix Pharmaceuticals) targets carbonic anhydrase IX (CAIX), which is highly expressed in ccRCC but not in other renal-mass pathologies (oncocytoma, papillary or chromophobe RCC, angiomyolipoma). Non-invasive discrimination of ccRCC from these mimics could reduce unnecessary biopsies and nephrectomies and guide a choice between surveillance and surgery for small renal masses - though as of this record's date the agent had not yet received a marketing authorisation.","asOf":"2026-09-22","links":[{"label":"PubMed: ZIRCON trial (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Telix Pharmaceuticals: ZIRCON results announcement","url":"https://telixpharma.com/news-views/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology/"}],"tags":["renal cell carcinoma","PET imaging","CAIX"],"related":["girentuximab-zr89","caix-pet","rcc","immuno-pet","telix","zr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2024,"doi":"10.1016/S1470-2045(24)00402-9","pmid":"39270701","authors":"Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, et al.","paperType":"rct","findings":["Mean sensitivity for ccRCC detection: 85.5% (95% CI 81.5-89.6); mean specificity: 87.0% (95% CI 81.0-93.1) across three blinded central readers.","Positive predictive value approximately 93%, including in small and difficult-to-detect lesions (per company summary of the same dataset).","No treatment-related deaths; most adverse events (74%) occurred during or after surgery and were unrelated to the tracer.","Most common grade 3+ adverse events were post-procedural haemorrhage (2%), urinary retention (1%) and hypertension (1%), attributable to the surgery rather than the tracer."],"whatItMeans":"A single injection and a PET scan five days later can identify clear-cell kidney cancer accurately enough to help decide whether someone with a suspicious kidney lump needs surgery, avoiding some biopsies and unnecessary operations.","caveats":["All participants were already scheduled for nephrectomy, so the trial does not directly show the agent changes management in a broader population of patients under surveillance.","As of the paper's publication the agent (TLX250-CDx / Zircaix) was investigational, not approved by FDA or EMA.","Performance in masses larger than 7 cm, or in patients unfit for surgery, was not the focus of this trial."],"changedPractice":false,"participants":300}]