{"id":"radiopharma-roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/","eras":[{"era":"1946-2000","title":"Radioiodine and early radioimmunotherapy","description":"131I cures differentiated thyroid cancer, the first theranostic. Strontium-89 and samarium-153 palliate bone pain. 90Y-ibritumomab and 131I-tositumomab (2002-03) work in lymphoma but fail commercially.","status":"historic","refs":[{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/","tldr":"Thyroid cancer is usually curable with surgery and radioactive iodine, the original theranostic. Rare aggressive forms respond to RET and BRAF inhibitors."}],"trials":[],"papers":[]},{"era":"2013-2018","title":"Radium-223 and Lutathera","description":"Radium-223 (ALSYMPCA, 2013) is the first alpha emitter approved, for bone metastases. 177Lu-DOTATATE (NETTER-1, 2018) establishes the modern peptide receptor radionuclide therapy paradigm with a matched 68Ga-DOTATATE PET.","status":"historic","refs":[{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/","status":"approved","tldr":"Lutetium-177 dotatate was the first modern radioligand therapy (2018), for neuroendocrine tumours, and is now used in first line."},{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/","tldr":"Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care."}],"trials":[],"papers":[]},{"era":"2020-2022","title":"PSMA theranostics","description":"PSMA PET approved (68Ga-PSMA-11 2020, Pylarify 2021); Pluvicto approved (VISION, 2022). Novartis builds the first radioligand commercial franchise; supply and site-capacity constraints appear.","status":"current","refs":[{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/","status":"standard-of-care","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."},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/","status":"approved","tldr":"A radioactive drug that seeks out PSMA on prostate cancer cells; the best-selling radiopharmaceutical ever."},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/","status":"positive","tldr":"VISION was the trial that established radioligand therapy in prostate cancer."},{"id":"pylarify","kind":"drug","name":"Piflufolastat F-18 / Pylarify TruVu","route":"/drugs/pylarify/","status":"approved","tldr":"Piflufolastat F-18 (Pylarify) is the leading PSMA PET tracer for prostate cancer, with a new formulation approved in March 2026."}],"trials":[{"id":"vision","name":"VISION","route":"/trials/vision/","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care","n":551,"value":15.3},{"name":"Standard care","n":280,"value":11.3}],"hr":0.62,"ci":[0.52,0.74],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"},{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617 + standard care","value":8.7},{"name":"Standard care","value":3.4}],"hr":0.4,"ci":[0.29,0.57],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"}],"setting":"PSMA+ metastatic castration-resistant prostate cancer after ARPI and taxane: 177Lu-PSMA-617 + SOC vs SOC","enrolled":861,"enrolledBasis":"registry"}],"papers":[]},{"era":"2023-2026","title":"Earlier lines, consolidation, and an M&A wave","description":"PSMAfore moves Pluvicto pre-chemotherapy (2025), NETTER-2 moves Lutathera to first line (2024); 2026 label expansions. BMS buys RayzeBio ($4.1B), AstraZeneca buys Fusion ($2.4B), Lilly buys Point; Bayer, Sanofi, Novartis expand. Pylarify TruVu approved March 2026. ITM-11 reads out a positive phase 3.","status":"current","refs":[{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/","status":"positive","tldr":"PSMAfore moved Pluvicto before chemotherapy in prostate cancer."},{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","route":"/drugs/ryz101/","status":"phase-3","tldr":"An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version."},{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","route":"/companies/fusion-pharma/","tldr":"Alpha-emitter company acquired by AstraZeneca ($2.4B, 2024); FPI-2265 (225Ac-PSMA-I&T) in phase 3."},{"id":"rayzebio","kind":"company","name":"RayzeBio (BMS)","route":"/companies/rayzebio/","tldr":"RayzeBio is the actinium-225 radiopharma company that BMS bought for $4.1B; its RYZ101 is in phase 3."},{"id":"itm","kind":"company","name":"ITM Isotope Technologies Munich","route":"/companies/itm/","tldr":"ITM is the largest non-carrier-added lutetium-177 supplier and the developer of ITM-11 (177Lu-edotreotide)."}],"trials":[{"id":"psmafore","name":"PSMAfore","route":"/trials/psmafore/","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PSMA-617","n":234,"value":12},{"name":"ARPI switch","n":234,"value":5.6}],"hr":0.41,"ci":[0.29,0.56],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"},{"endpoint":"Overall survival (crossover-adjusted)","unit":"months","arms":[{"name":"177Lu-PSMA-617","note":"Unadjusted OS HR 0.98 with 84% crossover from control"},{"name":"ARPI switch"}],"hr":0.59,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/fulltext"}],"setting":"PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch","enrolled":469,"enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2029","title":"Alpha emitters and new targets","description":"225Ac-PSMA (Novartis, Bayer Trillium, Fusion FPI-2265), 225Ac-DOTATATE (RYZ101) and 212Pb-DOTAMTATE are in phase 3; FAP radioligands (FAP-2286) are in phase 2; GRPR, CAIX, B7-H3, DLL3 radioconjugates are in early trials. TerraPower's Philadelphia Ac-225 plant aims for a 20-fold supply increase. Dosimetry-guided dosing enters trials.","status":"emerging","refs":[{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/","status":"phase-3","tldr":"Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply."},{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","route":"/drugs/ryz101/","status":"phase-3","tldr":"An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version."},{"id":"fap-2286","kind":"drug","name":"FAP-2286 (177Lu / 68Ga)","route":"/drugs/fap-2286/","status":"phase-2","tldr":"A FAP-targeted theranostic pair: one version images almost any solid tumour, the other treats it with radiation."},{"id":"terrapower-isotopes","kind":"company","name":"TerraPower Isotopes","route":"/companies/terrapower-isotopes/","tldr":"Bill Gates-backed producer of actinium-225 from thorium-229, building a Philadelphia facility to raise supply 20-fold."},{"id":"orano-med","kind":"company","name":"Orano Med","route":"/companies/orano-med/","tldr":"Orano Med is the leading lead-212 producer and the developer of 212Pb-DOTAMTATE (AlphaMedix)."},{"id":"dosimetry","kind":"term","name":"Dosimetry","route":"/terms/dosimetry/","tldr":"Measuring how much radiation dose each organ and tumour actually received from a radioactive drug."}],"trials":[],"papers":[]},{"era":"2029+","title":"Speculative: radioligands as a standard modality","description":"Alpha therapy in hormone-sensitive prostate cancer and after ADC failure; pan-cancer FAP theranostics; radio-ADCs and pretargeting; combination with PARP inhibitors, IO, and ADCs; automated decentralised radiopharmacies; total-body PET for ultra-low-dose dosimetry.","status":"speculative","refs":[{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/","status":"phase-2","tldr":"Attaching a radioactive atom to an antibody, so an ADC's targeting is used to deliver radiation instead of chemotherapy."},{"id":"beta-then-alpha","kind":"pairing","name":"Beta radioligand → alpha radioligand","route":"/pairings/beta-then-alpha/","tldr":"After lutetium therapy stops working, an actinium version of the same drug can still produce responses."},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/","status":"standard-of-care","tldr":"PET and CT in one machine, so hot spots on the PET are pinned to exact locations on the CT."}],"trials":[],"papers":[]}],"watch":[]}