# Beta radioligand → alpha radioligand

Source: https://onco.cc/pairings/beta-then-alpha/  
OnCo record `beta-then-alpha` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After lutetium therapy stops working, an actinium version of the same drug can still produce responses.

## Summary

This sequence pairing follows Radioligand therapy (beta emitters) with Targeted alpha therapy using the same targeting molecule: after lutetium stops working, an actinium version of the same drug can still produce responses. Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic or small-volume disease cannot repair, as explained in the Alpha vs beta emitters entry. In Prostate cancer, Actinium-225 PSMA agents after Lutetium-177 vipivotide tetraxetan produced PSA responses in retrospective series, and phase 3 trials (AcTION, AlphaBreak) are ongoing. In Neuroendocrine tumours, Actinium-225 DOTATATE (RYZ101) is being tested in ACTION-1 after Lutetium-177 dotatate, so the evidence is retrospective and phase 1/2 with phase 3 pending.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Radioligand therapy (beta emitters) + Targeted alpha therapy
- Type: sequence
- Rationale: Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic, or small-volume disease cannot repair.
- Evidence: Retrospective and phase 1/2; phase 3 pending.

## Sources

- ClinicalTrials.gov NCT06402331: AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617): https://clinicaltrials.gov/study/NCT06402331

## Connected records

- cancers: [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- drugs: [Actinium-225 DOTATATE](https://onco.cc/drugs/ryz101/), [Actinium-225 PSMA agents](https://onco.cc/drugs/ac225-psma/), [Lutetium-177 dotatate](https://onco.cc/drugs/lutathera/), [Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/)
- terms: [Alpha vs beta emitters](https://onco.cc/terms/alpha-vs-beta/)
- technologies: [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/), [Targeted alpha therapy](https://onco.cc/technologies/targeted-alpha-therapy/)
- roadmaps: [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://onco.cc/roadmaps/radiopharma-roadmap/)

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