# Actinium-225 DOTATATE

Source: https://nuclide.cc/drugs/ryz101/  
Nuclide record `ryz101` (Agent). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version.

## Summary

RYZ101 is actinium-225 DOTATATE, a targeted alpha therapy: the same SSTR2-binding peptide as Lutathera but chelating 225Ac, whose alpha decay chain delivers dense, short-range double-strand DNA breaks that beta particles cannot match. Bristol Myers Squibb acquired it with RayzeBio in 2024 for $4.1B. The ACTION-1 phase 3 trial tests it in SSTR-positive GEP-NETs progressing after 177Lu-SSTR therapy, at 10.5 MBq/kg every 8 weeks for 4 cycles, and it is also being combined with chemo-immunotherapy in extensive-stage small-cell lung cancer. Nausea, fatigue and lymphopenia are expected, and renal function is monitored because the kidneys clear the peptide. Whether alpha emission overcomes resistance to beta therapy, and whether 225Ac supply can meet demand, are the open questions. For a newcomer: an alpha-particle upgrade of an approved neuroendocrine radioligand.

## Fields

- Kind: Agent
- Status: phase-3
- Last checked: 2026-09-04
- Code: RYZ101
- Modality: Targeted alpha therapy
- Mechanism: DOTATATE chelating 225Ac; alpha decay chain.
- Dosing: IV infusion; 10.5 MBq/kg every 8 weeks for 4 cycles (ACTION-1)

## Sources

- ClinicalTrials.gov: trials of Actinium-225 DOTATATE: https://clinicaltrials.gov/search?intr=RYZ101

## Connected records

- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- indications: [Neuroendocrine tumours](https://nuclide.cc/indications/neuroendocrine/), [Pancreatic neuroendocrine tumours](https://nuclide.cc/indications/pancreatic-net/), [Small intestinal neuroendocrine tumours](https://nuclide.cc/indications/small-intestinal-net/), [Small-cell lung cancer](https://nuclide.cc/indications/sclc/)
- 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/), [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- targets: [Somatostatin receptor 2](https://nuclide.cc/targets/sstr2/)
- companies: [Bristol Myers Squibb](https://nuclide.cc/companies/bms/), [RayzeBio (BMS)](https://nuclide.cc/companies/rayzebio/)
- trials: [ACTION-1](https://nuclide.cc/trials/action-1/), [Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.](https://nuclide.cc/trials/nct06590857/)
- pairings: [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/), [Neuro-oncology imaging roadmap: FDG PET → amino acid PET → SSTR2 theranostics in meningioma](https://nuclide.cc/roadmaps/neuro-imaging-roadmap/), [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://nuclide.cc/roadmaps/radiopharma-roadmap/), [SSTR theranostics roadmap: octreotide scintigraphy → 68Ga-DOTATATE → 177Lu-DOTATATE → alpha](https://nuclide.cc/roadmaps/sstr-theranostics-roadmap/)
- ideas: [Recover legacy radium-226 sources worldwide as the feedstock for actinium-225](https://nuclide.cc/ideas/idea-reg-legacy-radium-recovery-ac225/)
- bottlenecks: [Actinium-225 supply](https://nuclide.cc/bottlenecks/b-ac225-supply/), [Clinical trial capacity for radioligand therapy](https://nuclide.cc/bottlenecks/b-rlt-trial-capacity/)
- fronts: [Targeted alpha therapy](https://nuclide.cc/fronts/f-alpha-therapy/)

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