# Actinium-225 PSMA agents

Source: https://nuclide.cc/drugs/ac225-psma/  
Nuclide record `ac225-psma` (Agent). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Agent
- Status: phase-3
- Last checked: 2026-09-04
- 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.
- Dosing: IV infusion; Trial regimens ~100 kBq/kg every 6-8 weeks

## Sources

- ClinicalTrials.gov: trials of Actinium-225 PSMA agents: https://clinicaltrials.gov/search?intr=225Ac-PSMA-617

## Connected records

- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/)
- indications: [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/), [Prostate cancer](https://nuclide.cc/indications/prostate/)
- technologies: [Actinium-225 supply: thorium stocks, accelerators and radium targets](https://nuclide.cc/technologies/actinium-225-supply/), [Alpha-emitter daughter redistribution ('free daughter' problem)](https://nuclide.cc/technologies/alpha-daughter-redistribution/), [Macropa chelation](https://nuclide.cc/technologies/macropa-chelation/), [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- targets: [PSMA](https://nuclide.cc/targets/psma/)
- companies: [AstraZeneca](https://nuclide.cc/companies/astrazeneca/), [Bayer](https://nuclide.cc/companies/bayer/), [Fusion Pharmaceuticals (AstraZeneca)](https://nuclide.cc/companies/fusion-pharma/), [Novartis](https://nuclide.cc/companies/novartis/)
- trials: [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://nuclide.cc/trials/alphabreak/), [Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer](https://nuclide.cc/trials/nct07590934/)
- pairings: [177Lu-PSMA-617 then 225Ac-PSMA rescue therapy](https://nuclide.cc/pairings/beta-psma-then-alpha-psma-rescue/), [Beta radioligand → alpha radioligand](https://nuclide.cc/pairings/beta-then-alpha/)
- roadmaps: [Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline](https://nuclide.cc/roadmaps/alpha-therapy-roadmap/), [PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha](https://nuclide.cc/roadmaps/psma-theranostics-roadmap/), [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://nuclide.cc/roadmaps/radiopharma-roadmap/)
- ideas: [Alpha-emitting PSMA therapy at first metastatic diagnosis](https://nuclide.cc/ideas/idea-alpha-first-mhspc/), [Alpha-emitting PSMA therapy for oligometastatic (few-lesion) prostate cancer](https://nuclide.cc/ideas/idea-alpha-for-oligometastatic-disease/), [Recover legacy radium-226 sources worldwide as the feedstock for actinium-225](https://nuclide.cc/ideas/idea-reg-legacy-radium-recovery-ac225/)
- people: [Clemens Kratochwil](https://nuclide.cc/people/clemens-kratochwil/)
- bottlenecks: [Actinium-225 supply](https://nuclide.cc/bottlenecks/b-ac225-supply/), [Manufacturing cost and time for living and radioactive medicines](https://nuclide.cc/bottlenecks/b-manufacturing-cell-therapy/)
- fronts: [Targeted alpha therapy](https://nuclide.cc/fronts/f-alpha-therapy/)
- key papers: [225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer](https://nuclide.cc/key-papers/paper-kratochwil-ac225-psma-jnm-2016/), [Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC](https://nuclide.cc/key-papers/paper-tagawa-ac225-j591-jco-2024/)

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