{"entity":{"id":"idea-accelerator-ac225-at-scale","kind":"idea","name":"Scaling actinium-225 supply with proton accelerators instead of the thorium-229 cow","aka":[],"tldr":"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.\n\nIn 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.\n\nA 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.","asOf":"2026-09-22","links":[{"label":"Production Methods for Ac-225 (DOE Isotope Program)","url":"https://www.isotopes.gov/information/actinium-225"},{"label":"Tri-Lab effort makes strides toward increasing supply of Ac-225 (ORNL news, 2021)","url":"https://www.ornl.gov/news/tri-lab-effort-makes-strides-toward-increasing-supply-ac-225-0"},{"label":"Streamlined Actinium-225 Processing through new All-Purpose Hot Cells (DOE Isotope Program, 2023)","url":"https://isotopes.gov/BNL-AP-Hot-Cells"},{"label":"Accelerating Production of Non-Carrier Added Actinium-225 (NorthStar technical report)","url":"https://www.northstarnm.com/wp-content/uploads/2023/11/Accelerating-Production-of-Non-Carrier-Added-Actinium-225-n.c.a.-Ac-225.pdf"},{"label":"DOE Isotope Program virtual roundtable with NRC on accelerator-produced Ac-225","url":"https://isotopes.gov/NRC-roundtable"}],"tags":["isotope supply","actinium-225","manufacturing"],"related":["actinium-225-supply","northstar-medical-radioisotopes","idea-reg-ac225-accelerator-pharmacopoeia","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"large","horizonYears":5},"route":"/ideas/idea-accelerator-ac225-at-scale/","neighbours":{"technology":[{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/"}],"company":[{"id":"northstar-medical-radioisotopes","kind":"company","name":"NorthStar Medical Radioisotopes","route":"/companies/northstar-medical-radioisotopes/"}],"idea":[{"id":"idea-reg-ac225-accelerator-pharmacopoeia","kind":"idea","name":"Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit","route":"/ideas/idea-reg-ac225-accelerator-pharmacopoeia/"}],"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"}]}}