{"entity":{"id":"f-alpha-therapy","kind":"section","name":"Targeted alpha therapy","aka":[],"tldr":"Alpha therapy uses a heavier type of radioactive particle that travels only a few cell widths but hits much harder, aimed at cancer cells that have stopped responding to the gentler beta-particle treatments.","summary":"Targeted alpha therapy (TAT) conjugates an alpha-emitting radionuclide, most often actinium-225, to the same PSMA or somatostatin-receptor ligands used in beta radioligand therapy. Alpha particles have a short tissue range (tens of micrometres, a few cell diameters) but a much higher linear energy transfer than beta particles, so they cause dense, largely non-repairable double-strand DNA breaks. Radium-223 (Alpharadin), an alpha-emitting bone-seeking agent, was the first alpha emitter approved in oncology, on the basis of the ALSYMPCA trial (improved overall survival and delayed skeletal-related events in bone-predominant mCRPC).\n\nFor tumour-targeted alpha therapy, 225Ac-PSMA agents (including Fusion Pharmaceuticals' FPI-2265 in the AlphaBreak programme, and RayzeBio/BMS's RYZ101, 225Ac-DOTATATE, for neuroendocrine tumours) are in phase 1/2 development, largely in patients who progressed on or are refractory to lutetium-177 therapy. A 2026 systematic review and meta-analysis (Belabaci et al., Eur J Nucl Med Mol Imaging 2026) assessed combined 225Ac/177Lu-PSMA therapy but the field still lacks randomised phase 3 evidence for any alpha-PSMA agent.\n\nThe defining unsolved problem is supply, not biology: global 225Ac production is estimated at roughly 63 GBq (1.7 Ci) per year, sufficient for only about 100-200 patients annually, against an estimated clinical and trial demand of around 185 GBq/year and rising (Alpha Atlas / IAEA TECDOC-2057, 2024). Production depends on a handful of 229Th generators (Oak Ridge National Laboratory, the EU Joint Research Centre in Karlsruhe, and Russia's IPPE) or on cyclotron irradiation of 226Ra, and the IAEA's Global Radium-226 Management Initiative is recovering legacy radium sources from around 80 countries as an alternative feedstock. Xerostomia (salivary gland uptake) and dosimetric uncertainty are the main clinical limitations reported so far.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC-2057: Production and quality control of actinium-225 radiopharmaceuticals (2024)","url":"https://www-pub.iaea.org/MTCD/publications/PDF/TE-2057web.pdf"},{"label":"ALSYMPCA trial (Parker et al., NEJM 2013)","url":"https://www.nejm.org/doi/10.1056/NEJMoa1213755"},{"label":"IAEA: Global Radium-226 Management Initiative update (ANS, Jan 2026)","url":"https://www.ans.org/news/2026-01-14/article-7675/iaeas-global-radium226-management-initiative-continues-to-progress/"},{"label":"Actinium-225/Bismuth-213 supply and application barriers (Cancers, 2025)","url":"https://www.mdpi.com/2072-6694/17/18/3055"}],"tags":[],"related":["f-radioligand-therapy","f-isotope-supply","f-bone-targeted","lu-177","ac-225","ra-223"],"indications":["prostate-mcrpc","neuroendocrine","metastatic-ppgl"],"sections":[],"technologies":["targeted-alpha-therapy","actinium-225-supply","astatine-211-alpha-therapy","alpha-nanogenerators"],"targets":[],"drugs":["ac225-psma","fpi-2265","ryz101","alphamedix","radium-223"],"companies":["fusion-pharma","rayzebio","perspective-therapeutics","orano-med","actinium-pharmaceuticals","artbio","convergent-therapeutics"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":["alsympca","alphabreak","nct05219500"],"people":[],"bottlenecks":[],"keyPapers":["paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":["Global 225Ac supply (~63 GBq/year) covers only about 100-200 patient treatments a year against an estimated demand of ~185 GBq/year and rising (IAEA TECDOC-2057, 2024).","No alpha-PSMA agent has randomised phase 3 evidence yet; current clinical use is investigational or salvage after lutetium-177.","The IAEA's Global Radium-226 Management Initiative is recovering legacy radium sources from roughly 80 countries as feedstock for 225Ac, a genuinely new supply route rather than incremental reactor capacity."],"order":3},"route":"/fronts/f-alpha-therapy/","neighbours":{"section":[{"id":"f-bone-targeted","kind":"section","name":"Bone-targeted radiopharmaceuticals","route":"/fronts/f-bone-targeted/"},{"id":"f-isotope-supply","kind":"section","name":"Isotope supply","route":"/fronts/f-isotope-supply/"},{"id":"f-radioligand-therapy","kind":"section","name":"Radioligand therapy","route":"/fronts/f-radioligand-therapy/"}],"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"},{"id":"ra-223","kind":"isotope","name":"Radium-223","route":"/isotopes/ra-223/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"},{"id":"metastatic-ppgl","kind":"indication","name":"Metastatic pheochromocytoma and paraganglioma","route":"/indications/metastatic-ppgl/"},{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"}],"technology":[{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/"},{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","route":"/technologies/alpha-nanogenerators/"},{"id":"astatine-211-alpha-therapy","kind":"technology","name":"Astatine-211 alpha therapy","route":"/technologies/astatine-211-alpha-therapy/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"drug":[{"id":"alphamedix","kind":"drug","name":"212Pb-DOTAMTATE","route":"/drugs/alphamedix/"},{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","route":"/drugs/ryz101/"},{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/"},{"id":"fpi-2265","kind":"drug","name":"FPI-2265","route":"/drugs/fpi-2265/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"}],"company":[{"id":"actinium-pharmaceuticals","kind":"company","name":"Actinium Pharmaceuticals","route":"/companies/actinium-pharmaceuticals/"},{"id":"artbio","kind":"company","name":"ARTBIO","route":"/companies/artbio/"},{"id":"convergent-therapeutics","kind":"company","name":"Convergent Therapeutics","route":"/companies/convergent-therapeutics/"},{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","route":"/companies/fusion-pharma/"},{"id":"orano-med","kind":"company","name":"Orano Med","route":"/companies/orano-med/"},{"id":"perspective-therapeutics","kind":"company","name":"Perspective Therapeutics","route":"/companies/perspective-therapeutics/"},{"id":"rayzebio","kind":"company","name":"RayzeBio (BMS)","route":"/companies/rayzebio/"}],"term":[{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","route":"/terms/alpha-vs-beta/"}],"trial":[{"id":"alphabreak","kind":"trial","name":"AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","route":"/trials/alphabreak/"},{"id":"alsympca","kind":"trial","name":"ALSYMPCA","route":"/trials/alsympca/"},{"id":"nct05219500","kind":"trial","name":"Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST).","route":"/trials/nct05219500/"}],"paper":[{"id":"paper-alsympca-radium-223-nejm-2013","kind":"paper","name":"ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases","route":"/key-papers/paper-alsympca-radium-223-nejm-2013/"}]}}