# Scaling actinium-225 supply with proton accelerators instead of the thorium-229 cow

Source: https://nuclide.cc/ideas/idea-accelerator-ac225-at-scale/  
Nuclide record `idea-accelerator-ac225-at-scale` (Idea). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Most of the world's actinium-225, a rare radioactive metal used in some newer cancer treatments, comes from slowly extracting it from an old stockpile of another radioactive element. A different method — firing high-energy protons at ordinary thorium metal in an accelerator — can make much bigger batches, needed if actinium-225 treatments are ever to reach more than a small number of patients.

## Summary

Historically, essentially all of the world's actinium-225 has come from 'milking' a legacy stockpile of thorium-229 (itself derived from uranium-233), a process that yields only about 1-1.2 curies a year worldwide, enough for roughly 1,000-1,200 patients and far too little to run more than the most preliminary clinical trials. The US Department of Energy's Isotope Program established the Ac-225 Tri-Lab Effort in 2014-2015 across Brookhaven, Los Alamos and Oak Ridge National Laboratories to develop an alternative: firing high-energy (greater than 70 MeV) proton beams at thorium-232 targets to produce actinium-225 by spallation, a reaction that does not depend on the finite thorium-229/uranium-233 stockpile.

In June 2021, Brookhaven demonstrated that this accelerator route could generate about 60% of the entire annual thorium-229-derived supply in a single 12-day irradiation and processing campaign. The FDA accepted a Type II Drug Master File for accelerator-produced actinium-225 nitrate from Oak Ridge National Laboratory in January 2020, and the Tri-Lab effort has since distributed more than 1,100 millicuries of accelerator-produced actinium-225 to evaluators, with batch sizes targeted to grow from the historical 50-100 mCi range toward 100-1,000 mCi per batch. Brookhaven completed an $8.5 million refurbishment of its All-Purpose Hot Cell facility in March 2023 specifically to expand actinium-225 processing capacity, and separately NorthStar Medical Radioisotopes has pursued a different accelerator route (electron-beam photonuclear transmutation of radium-226) intended to produce up to 200 curies a year per accelerator.

A known trade-off of the proton-spallation route is co-production of actinium-227, a long-lived (22-year) alpha emitter; the DOE Isotope Program states this is kept to 2% or less of total activity at product release, and held a joint roundtable with the US Nuclear Regulatory Commission in March 2023 to work through the regulatory implications of that impurity for hospitals and clinics using the material.

## Fields

- Kind: Idea
- Last checked: 2026-09-22
- Tags: isotope supply; actinium-225; manufacturing
- Hypothesis: Producing actinium-225 by proton-beam spallation of thorium-232 in linear accelerators, rather than extracting it from the legacy thorium-229 stockpile, can scale world supply from roughly 1-1.2 curies a year to the hundreds-of-curies scale needed for large randomized trials and eventual commercial radioligand therapy.
- Rationale: The DOE Tri-Lab effort demonstrated in 2021 that a single 12-day accelerator campaign could produce about 60% of the entire annual thorium-229-derived supply, and the FDA has already accepted a Drug Master File for the accelerator-produced material, showing the regulatory pathway is viable. The main open questions are whether batch sizes can be sustained at the 100-1,000 mCi scale needed for a registrational trial, and how regulators and clinics will handle the co-produced, long-lived actinium-227 impurity.
- Proposed test: The 2021 Brookhaven demonstration campaign already showed technical feasibility at scale; the next milestone is whether the renovated Brookhaven All-Purpose Hot Cell facility and expanded Los Alamos target capacity sustain routine batches in the hundreds of millicuries, and whether an actinium-225 radioligand therapy programme can complete a registrational trial supplied entirely from accelerator-produced material under an agreed actinium-227 impurity limit.
- Maturity: being-tested-at-scale
- Actor: engineering

## Sources

- Production Methods for Ac-225 (DOE Isotope Program): https://www.isotopes.gov/information/actinium-225
- Tri-Lab effort makes strides toward increasing supply of Ac-225 (ORNL news, 2021): https://www.ornl.gov/news/tri-lab-effort-makes-strides-toward-increasing-supply-ac-225-0
- Streamlined Actinium-225 Processing through new All-Purpose Hot Cells (DOE Isotope Program, 2023): https://isotopes.gov/BNL-AP-Hot-Cells
- Accelerating Production of Non-Carrier Added Actinium-225 (NorthStar technical report): https://www.northstarnm.com/wp-content/uploads/2023/11/Accelerating-Production-of-Non-Carrier-Added-Actinium-225-n.c.a.-Ac-225.pdf
- DOE Isotope Program virtual roundtable with NRC on accelerator-produced Ac-225: https://isotopes.gov/NRC-roundtable

## Connected records

- technologies: [Actinium-225 supply: thorium stocks, accelerators and radium targets](https://nuclide.cc/technologies/actinium-225-supply/)
- companies: [NorthStar Medical Radioisotopes](https://nuclide.cc/companies/northstar-medical-radioisotopes/)
- ideas: [Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit](https://nuclide.cc/ideas/idea-reg-ac225-accelerator-pharmacopoeia/)
- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/)

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