{"entity":{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","aka":[],"tldr":"Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply.","summary":"Novartis (225Ac-PSMA-617, phase 3 AcTION), Bayer (225Ac-PSMA-Trillium with albumin binder, PAnTHA phase 1 at ASCO GU 2026), Fusion/AstraZeneca (FPI-2265, 225Ac-PSMA-I&T, phase 3 AlphaBreak), and academic 225Ac-PSMA data from South Africa and Germany. Xerostomia from salivary uptake is dose-limiting.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Actinium-225 PSMA agents","url":"https://clinicaltrials.gov/search?intr=225Ac-PSMA-617"}],"tags":[],"related":["ac-225"],"indications":["prostate","prostate-mcrpc"],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":["psma"],"drugs":[],"companies":["novartis","bayer","fusion-pharma","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07590934"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"225Ac-PSMA-617, 225Ac-PSMA-I&T, BAY 3563254 (Trillium)","modality":"Targeted alpha therapy","mechanism":"PSMA ligand with 225Ac; four alpha emissions per decay chain.","approvals":[],"mechanismSteps":["Radioligand circulates and binds PSMA on tumour cells","Ligand is internalised or retained at the membrane","Alpha (225Ac) emissions deposit energy within a short range","Clustered DNA double-strand breaks form in the tumour cell and its neighbours (crossfire)","Cells die; unbound ligand is cleared via the kidneys"],"dosing":{"route":"IV infusion","schedule":"Trial regimens ~100 kBq/kg every 6-8 weeks","monitoring":"Salivary gland toxicity (xerostomia), renal function, blood counts","source":"https://clinicaltrials.gov"},"toxicity":[{"event":"Xerostomia","note":"Dose-limiting in academic series"},{"event":"Anaemia"},{"event":"Thrombocytopenia"},{"event":"Renal toxicity"}],"access":[{"country":"US","reimbursement":"Investigational (phase 3)","asOf":"2026-09-06"},{"country":"DE","reimbursement":"Compassionate use at selected centres (Heidelberg and others)","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-06","type":"filing","region":"US","note":"AstraZeneca completes Fusion Pharmaceuticals acquisition; FPI-2265 phase 3 planned","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/ac225-psma/","neighbours":{"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"technology":[{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/"},{"id":"alpha-daughter-redistribution","kind":"technology","name":"Alpha-emitter daughter redistribution ('free daughter' problem)","route":"/technologies/alpha-daughter-redistribution/"},{"id":"macropa-chelation","kind":"technology","name":"Macropa chelation","route":"/technologies/macropa-chelation/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","route":"/companies/fusion-pharma/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"trial":[{"id":"alphabreak","kind":"trial","name":"AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","route":"/trials/alphabreak/"},{"id":"nct07590934","kind":"trial","name":"Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer","route":"/trials/nct07590934/"}],"pairing":[{"id":"beta-psma-then-alpha-psma-rescue","kind":"pairing","name":"177Lu-PSMA-617 then 225Ac-PSMA rescue therapy","route":"/pairings/beta-psma-then-alpha-psma-rescue/"},{"id":"beta-then-alpha","kind":"pairing","name":"Beta radioligand → alpha radioligand","route":"/pairings/beta-then-alpha/"}],"roadmap":[{"id":"alpha-therapy-roadmap","kind":"roadmap","name":"Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline","route":"/roadmaps/alpha-therapy-roadmap/"},{"id":"psma-theranostics-roadmap","kind":"roadmap","name":"PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha","route":"/roadmaps/psma-theranostics-roadmap/"},{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/"}],"idea":[{"id":"idea-alpha-first-mhspc","kind":"idea","name":"Alpha-emitting PSMA therapy at first metastatic diagnosis","route":"/ideas/idea-alpha-first-mhspc/"},{"id":"idea-alpha-for-oligometastatic-disease","kind":"idea","name":"Alpha-emitting PSMA therapy for oligometastatic (few-lesion) prostate cancer","route":"/ideas/idea-alpha-for-oligometastatic-disease/"},{"id":"idea-reg-legacy-radium-recovery-ac225","kind":"idea","name":"Recover legacy radium-226 sources worldwide as the feedstock for actinium-225","route":"/ideas/idea-reg-legacy-radium-recovery-ac225/"}],"person":[{"id":"clemens-kratochwil","kind":"person","name":"Clemens Kratochwil","route":"/people/clemens-kratochwil/"}],"bottleneck":[{"id":"b-ac225-supply","kind":"bottleneck","name":"Actinium-225 supply","route":"/bottlenecks/b-ac225-supply/"},{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"section":[{"id":"f-alpha-therapy","kind":"section","name":"Targeted alpha therapy","route":"/fronts/f-alpha-therapy/"}],"paper":[{"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","route":"/key-papers/paper-kratochwil-ac225-psma-jnm-2016/"},{"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","route":"/key-papers/paper-tagawa-ac225-j591-jco-2024/"}]}}