# Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline

Source: https://nuclide.cc/roadmaps/alpha-therapy-roadmap/  
Nuclide record `alpha-therapy-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Alpha particles carry much more energy over a much shorter distance than the beta particles used in Lutathera and Pluvicto, so they can be more powerful against small clusters of cancer cells. The first alpha drug was approved in 2013; a wave of alpha versions of existing beta drugs is now in late-stage testing, and the isotopes are still scarce.

## Summary

Alpha-particle therapy began clinically with radium-223 dichloride, approved by the FDA on 15 May 2013 for bone metastases in prostate cancer after the ALSYMPCA trial, though radium-223 is a bone-seeker rather than a targeted radioligand. The targeted-alpha era proper starts with Kratochwil and colleagues at Heidelberg and the Joint Research Centre Karlsruhe, who treated the first patients with 225Ac-PSMA-617 in 2014 and reported complete responses in two heavily pretreated men with metastatic castration-resistant prostate cancer in 2016, followed by empirical dose-finding in a larger series in 2017.

That compassionate-use experience seeded a pipeline of sponsor-run trials repeating the beta-to-alpha substitution across targets: 225Ac-DOTATATE (RYZ101, RayzeBio/BMS) in the ACTION-1 trial for neuroendocrine tumours progressing after 177Lu-DOTATATE; 225Ac-PSMA-I&T (FPI-2265, Fusion Pharmaceuticals/AstraZeneca) in AlphaBreak for prostate cancer after 177Lu-PSMA; 225Ac-PSMA-617 (AAA817, Novartis) in a phase 3 programme; and 212Pb-DOTAMTATE (AlphaMedix, RadioMedix/Orano Med/Sanofi), whose phase 2 ALPHAMEDIX-02 study reported that it met all primary efficacy endpoints in October 2025. Every one of these programmes is capacity-constrained: actinium-225 in particular is scarce, and lead-212 and actinium-225 production are both being scaled by companies such as TerraPower Isotopes and Orano Med.

The unresolved questions are whether alpha activity will translate into a survival benefit large enough for approval once the phase 3 readouts arrive (2026-2028 on current registry estimates), whether the added myelotoxicity and xerostomia seen in compassionate-use series are tolerable at scale, and whether supply can grow fast enough to support first-line or earlier-line use rather than remaining a last-resort option after beta radioligand therapy fails.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-22

## Sources

- FDA: Alsympca (radium-223 dichloride) approval, May 2013: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203971Orig1s000TOC.cfm
- Kratochwil et al., 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy (J Nucl Med 2016): https://pubmed.ncbi.nlm.nih.gov/27390158/
- RayzeBio/ClinicalTrials.gov: ACTION-1 (NCT05477576): https://clinicaltrials.gov/study/NCT05477576
- Sanofi: AlphaMedix (212Pb-DOTAMTATE) ALPHAMEDIX-02 phase 2 results, October 2025: https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053
- TerraPower Isotopes: Bellwether Laboratory groundbreaking, May 2026: https://www.terrapower.com/TerraPower-Isotopes-Breaks-Ground-on-Worlds-Largest-Actinium-225-Manufacturing-Facility-in-Philadelphia

## Connected records

- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Lead-212](https://nuclide.cc/isotopes/pb-212/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/), [Radium-223](https://nuclide.cc/isotopes/ra-223/)
- technologies: [Actinium-225 supply: thorium stocks, accelerators and radium targets](https://nuclide.cc/technologies/actinium-225-supply/), [Peptide receptor radionuclide therapy (PRRT)](https://nuclide.cc/technologies/prrt/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/), [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- drugs: [212Pb-DOTAMTATE](https://nuclide.cc/drugs/alphamedix/), [Actinium-225 DOTATATE](https://nuclide.cc/drugs/ryz101/), [Actinium-225 PSMA agents](https://nuclide.cc/drugs/ac225-psma/), [FPI-2265](https://nuclide.cc/drugs/fpi-2265/), [Radium-223 dichloride](https://nuclide.cc/drugs/radium-223/)
- companies: [Fusion Pharmaceuticals (AstraZeneca)](https://nuclide.cc/companies/fusion-pharma/), [Novartis](https://nuclide.cc/companies/novartis/), [Orano Med](https://nuclide.cc/companies/orano-med/), [RadioMedix](https://nuclide.cc/companies/radiomedix/), [RayzeBio (BMS)](https://nuclide.cc/companies/rayzebio/), [TerraPower Isotopes](https://nuclide.cc/companies/terrapower-isotopes/)
- trials: [ACTION-1](https://nuclide.cc/trials/action-1/), [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://nuclide.cc/trials/alphabreak/), [ALPHAMEDIX-02](https://nuclide.cc/trials/alphamedix-02/), [ALSYMPCA](https://nuclide.cc/trials/alsympca/)
- people: [Clemens Kratochwil](https://nuclide.cc/people/clemens-kratochwil/), [Uwe Haberkorn](https://nuclide.cc/people/uwe-haberkorn/)
- key papers: [ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases](https://nuclide.cc/key-papers/paper-alsympca-radium-223-nejm-2013/)
- ideas: [Alpha radioligands after ADC failure](https://nuclide.cc/ideas/idea-alpha-after-adc/), [Alpha-emitting PSMA therapy at first metastatic diagnosis](https://nuclide.cc/ideas/idea-alpha-first-mhspc/)

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