{"entity":{"id":"f-radioligand-therapy","kind":"section","name":"Radioligand therapy","aka":[],"tldr":"Radioligand therapy attaches a radioactive particle to a molecule that homes in on a tumour, so the radiation is delivered from the inside of the cancer rather than from an external beam.","summary":"Radioligand therapy (RLT) with beta-emitters is the most clinically mature branch of theranostics. Lutetium-177 vipivotide tetraxetan (Pluvicto, 177Lu-PSMA-617) is approved by the FDA and EMA for PSMA-positive metastatic castration-resistant prostate cancer, on the strength of the VISION trial (median overall survival 15.3 vs 11.3 months, HR 0.62; radiographic progression-free survival 8.7 vs 3.4 months, HR 0.40; Sartor et al., NEJM 2021) and the earlier-line PSMAfore trial (rPFS 9.3 vs 5.6 months, HR 0.41), which supported the FDA's March 2025 label expansion into taxane-naive mCRPC. Lutetium-177 dotatate (Lutathera) is approved for gastroenteropancreatic neuroendocrine tumours on the basis of NETTER-1 (Strosberg et al., NEJM 2017) and has since been extended to a first-line setting by NETTER-2 (Lancet 2024).\n\nA competitive multi-agent PSMA-RLT field is emerging behind Pluvicto: 177Lu-PSMA-I&T (PNT2002, Lantheus/POINT Biopharma) reported the SPLASH trial, and Telix's antibody-based rosopatamab tetraxetan (TLX591-Tx) is in the ProstACT Global phase 3 programme. On the neuroendocrine side, 177Lu-edotreotide (ITM-11) and FAP-targeted 177Lu-FAP-2286 are in later-phase development.\n\nWhat remains unsolved: a 2026 GRADE-assessed meta-analysis of six randomised trials (Mubarika et al., Int Urol Nephrol 2026) found the primary intention-to-treat overall-survival benefit of 177Lu-PSMA over standard of care was not statistically significant (HR 0.81, 95% CI 0.62-1.06), with a benefit only apparent after adjusting for control-arm crossover (HR 0.76, 95% CI 0.59-0.96) — a reminder that trial-design choices, not just the isotope, drive the reported benefit. Optimal sequencing against androgen-receptor pathway inhibitors, taxanes and alpha emitters is still being worked out in trials such as PSMAddition and ENZA-p, and lutetium-177's roughly 0.5-2 mm beta path length is thought to undertreat isolated tumour cells and micrometastases, motivating the move to alpha emitters.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto (accessdata.fda.gov)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf"},{"label":"VISION trial (Sartor et al., NEJM 2021)","url":"https://www.nejm.org/doi/10.1056/NEJMoa2107322"},{"label":"GRADE-assessed meta-analysis of 177Lu-PSMA RCTs (Int Urol Nephrol, 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/42570199/"},{"label":"Guideline of guidelines: 177Lu-PSMA RLT (BJU Int, 2026)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13458634/"}],"tags":[],"related":["f-molecular-imaging","f-alpha-therapy","f-dosimetry","lu-177"],"indications":["prostate-mcrpc","prostate-mhspc","neuroendocrine","small-intestinal-net","pancreatic-net","lung-net"],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy","prrt","peptide-drug-conjugate","psma-pet","sstr-pet"],"targets":[],"drugs":["pluvicto","lutathera","lu177-psma-it","itm-11","fap-2286"],"companies":["novartis","advanced-accelerator-applications","point-biopharma","lantheus","itm","telix"],"institutions":[],"pathways":[],"terms":["prrt-term","psa50","mcrpc-mhspc"],"trials":["vision","psmafore","netter-1","splash","psmaddition"],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021","paper-netter-1-nejm-2017","paper-netter-2-lancet-2024"],"journals":[],"dependsOn":[],"notes":["A 2026 GRADE meta-analysis found the ITT overall-survival benefit of 177Lu-PSMA vs standard of care was not significant (HR 0.81, 95% CI 0.62-1.06) until adjusted for crossover (HR 0.76, 95% CI 0.59-0.96); trial design materially changes the reported effect size.","Optimal sequencing of RLT against ARPIs, taxanes and alpha emitters is unresolved; PSMAddition and ENZA-p are testing earlier and combined use.","177Lu's beta path length (roughly 0.5-2 mm) is thought to leave isolated tumour cells and micrometastases undertreated, which is the main argument for moving to alpha emitters."],"order":2},"route":"/fronts/f-radioligand-therapy/","neighbours":{"section":[{"id":"f-bone-targeted","kind":"section","name":"Bone-targeted radiopharmaceuticals","route":"/fronts/f-bone-targeted/"},{"id":"f-dosimetry","kind":"section","name":"Dosimetry","route":"/fronts/f-dosimetry/"},{"id":"f-isotope-supply","kind":"section","name":"Isotope supply","route":"/fronts/f-isotope-supply/"},{"id":"f-molecular-imaging","kind":"section","name":"Molecular imaging","route":"/fronts/f-molecular-imaging/"},{"id":"f-alpha-therapy","kind":"section","name":"Targeted alpha therapy","route":"/fronts/f-alpha-therapy/"}],"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"indication":[{"id":"lung-net","kind":"indication","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/indications/lung-net/"},{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"},{"id":"prostate-mhspc","kind":"indication","name":"Metastatic hormone-sensitive prostate cancer","route":"/indications/prostate-mhspc/"},{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"},{"id":"pancreatic-net","kind":"indication","name":"Pancreatic neuroendocrine tumours","route":"/indications/pancreatic-net/"},{"id":"small-intestinal-net","kind":"indication","name":"Small intestinal neuroendocrine tumours","route":"/indications/small-intestinal-net/"}],"technology":[{"id":"lu177-radioligand-therapy","kind":"technology","name":"Lutetium-177 radioligand therapy","route":"/technologies/lu177-radioligand-therapy/"},{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","route":"/technologies/prrt/"},{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","route":"/technologies/peptide-drug-conjugate/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"sstr-pet","kind":"technology","name":"Somatostatin receptor PET (68Ga/64Cu-DOTATATE)","route":"/technologies/sstr-pet/"}],"drug":[{"id":"itm-11","kind":"drug","name":"177Lu-edotreotide","route":"/drugs/itm-11/"},{"id":"lu177-psma-it","kind":"drug","name":"177Lu-PSMA-I&T","route":"/drugs/lu177-psma-it/"},{"id":"fap-2286","kind":"drug","name":"FAP-2286 (177Lu / 68Ga)","route":"/drugs/fap-2286/"},{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"company":[{"id":"advanced-accelerator-applications","kind":"company","name":"Advanced Accelerator Applications (Novartis)","route":"/companies/advanced-accelerator-applications/"},{"id":"itm","kind":"company","name":"ITM Isotope Technologies Munich","route":"/companies/itm/"},{"id":"lantheus","kind":"company","name":"Lantheus","route":"/companies/lantheus/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"},{"id":"point-biopharma","kind":"company","name":"POINT Biopharma","route":"/companies/point-biopharma/"},{"id":"telix","kind":"company","name":"Telix Pharmaceuticals","route":"/companies/telix/"}],"term":[{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"},{"id":"prrt-term","kind":"term","name":"PRRT (peptide receptor radionuclide therapy)","route":"/terms/prrt-term/"},{"id":"psa50","kind":"term","name":"PSA50 / PSA90 response","route":"/terms/psa50/"}],"trial":[{"id":"netter-1","kind":"trial","name":"NETTER-1","route":"/trials/netter-1/"},{"id":"psmaddition","kind":"trial","name":"PSMAddition","route":"/trials/psmaddition/"},{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/"},{"id":"splash","kind":"trial","name":"SPLASH","route":"/trials/splash/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}],"paper":[{"id":"paper-netter-1-nejm-2017","kind":"paper","name":"NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide","route":"/key-papers/paper-netter-1-nejm-2017/"},{"id":"paper-netter-2-lancet-2024","kind":"paper","name":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","route":"/key-papers/paper-netter-2-lancet-2024/"},{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","route":"/key-papers/paper-vision-nejm-2021/"}]}}