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

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.