{"entity":{"id":"isotope-supply-roadmap","kind":"roadmap","name":"Isotope supply roadmap: reactor dependence → non-uranium production → accelerator-made actinium","aka":[],"tldr":"The radioactive ingredients that make theranostics work come from a small number of ageing nuclear reactors, generators and accelerators around the world. A shortage anywhere in that chain delays cancer scans and treatments; new non-uranium and accelerator-based production lines are being built to fix that, but they take years and hundreds of millions of dollars.","summary":"For decades the world's molybdenum-99 (the parent of technetium-99m, the workhorse of conventional nuclear medicine) came almost entirely from a handful of ageing research reactors using highly enriched uranium targets, concentrated in Canada, the Netherlands, Belgium, France and South Africa. When Canada's NRU reactor and the Netherlands' HFR both went offline for repairs in 2009-2010, the resulting shortage disrupted nuclear medicine services worldwide and triggered a policy response.\n\nThe US response, formalised in the American Medical Isotope Production Act of 2012, funded non-uranium domestic production. NorthStar Medical Radioisotopes' RadioGenix System, producing molybdenum-99 without highly enriched uranium via neutron capture at the University of Missouri Research Reactor, received FDA approval in February 2018, the first domestic Mo-99 production in roughly three decades. Lutetium-177 demand then rose sharply once Lutathera (2018) and Pluvicto (2022) were approved, straining the same reactor capacity and the enriched ytterbium-176 supply used for no-carrier-added production.\n\nThe newest constraint is actinium-225 for targeted alpha therapy, historically harvested in gram quantities from thorium-229 stockpiles. TerraPower Isotopes announced commercial-scale, weekly actinium-225 production in October 2024 using a natural decay method from thorium-229 recovered from US Department of Energy uranium-233 stocks, and in 2026 broke ground on a $450 million Philadelphia facility intended to increase global capacity twentyfold, with production expected from 2029. Whether reactor, cyclotron and accelerator capacity can keep pace with a growing radioligand pipeline, without a repeat of the 2009-2010 shortage, is the open question this roadmap tracks.","asOf":"2026-09-22","links":[{"label":"DOE/NNSA: FDA approval of domestically-produced, non-uranium based Mo-99, February 2018","url":"https://www.energy.gov/articles/doennsa-partnership-us-healthcare-industry-results-fda-approval-domestically-produced-non"},{"label":"TerraPower Isotopes: reaches market-scale production of actinium-225, October 2024","url":"https://www.terrapower.com/tpi-brings-actinium-225-to-market"},{"label":"TerraPower Isotopes: Bellwether Laboratory groundbreaking, May 2026","url":"https://www.terrapower.com/TerraPower-Isotopes-Breaks-Ground-on-Worlds-Largest-Actinium-225-Manufacturing-Facility-in-Philadelphia"},{"label":"NorthStar: FDA approves additional Mo-99 filling lines, February 2020","url":"https://www.itnonline.com/content/fda-approves-additional-molybdenum-99-mo-99-filling-lines-northstar-medical-radioisotopes"}],"tags":[],"related":["tc-99m","mo-99","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain","actinium-225-supply","cyclotron-isotope-production","radiopharmacy-network"],"targets":[],"drugs":[],"companies":["northstar-medical-radioisotopes","shine-technologies","terrapower-isotopes","orano-med","nordion","ire","ntp-radioisotopes","ansto","nusano"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1960s-2008","title":"Reactor-dependent, HEU-based supply","description":"Global molybdenum-99 supply concentrates in a small number of ageing, mostly HEU-fuelled research reactors (Canada's NRU, the Netherlands' HFR, Belgium's BR2, France's OSIRIS, South Africa's SAFARI-1), each serving large multi-country markets with no domestic US production.","refs":["research-reactor-isotope-production"],"status":"historic"},{"era":"2009-2010","title":"The global Mo-99 shortage","description":"NRU (Chalk River) and HFR both go offline for unplanned repairs at overlapping times, causing a worldwide shortage of molybdenum-99/technetium-99m that disrupts nuclear medicine imaging and prompts a US and international policy response to diversify supply.","refs":["research-reactor-isotope-production"],"status":"historic"},{"era":"2012-2018","title":"Non-HEU domestic Mo-99 production","description":"The American Medical Isotope Production Act (2012) directs the US Department of Energy/NNSA to fund non-HEU Mo-99 production. NorthStar Medical Radioisotopes' RadioGenix System, using neutron-capture production of Mo-99 at the University of Missouri Research Reactor, receives FDA approval on 8 February 2018, the first domestic, non-uranium Mo-99 production since the 1980s.","refs":["northstar-medical-radioisotopes"],"status":"historic"},{"era":"2018-2024","title":"Lutetium-177 demand outpaces capacity","description":"Approvals of Lutathera (2018) and Pluvicto (2022) sharply increase demand for reactor-produced lutetium-177, straining both irradiation capacity and the enriched ytterbium-176 supply used for no-carrier-added Lu-177 production; multiple national reactor operators (ANSTO, IRE, NTP Radioisotopes) expand production lines.","refs":["therapy-isotope-supply-chain","pluvicto","lutathera"],"status":"current"},{"era":"2024-2026","title":"Accelerator-made actinium-225 reaches commercial scale","description":"TerraPower Isotopes announces commercial-scale, weekly actinium-225 production from October 2024, using a natural decay method from thorium-229 recovered from US Department of Energy uranium-233 stockpiles in partnership with Isotek. In March 2026 the company announces a second, much larger facility in Philadelphia.","refs":["terrapower-isotopes","actinium-225-supply"],"status":"current"},{"era":"2026-2029","title":"Building twentyfold actinium-225 capacity","description":"TerraPower Isotopes breaks ground on its $450m Bellwether Laboratory in Philadelphia in May 2026, intended to increase global actinium-225 production capacity twentyfold alongside expansion at its Everett, Washington site; the Pennsylvania state government contributes grant funding. Production is expected to begin in 2029.","refs":["terrapower-isotopes"],"status":"emerging"},{"era":"2029+","title":"Speculative: a resilient, diversified isotope supply","description":"Proposals under discussion include Western enrichment of ytterbium-176 to add a second Lu-177 supplier, a coordinated international reserve and shared schedule for medical isotope reactors, regional radiopharmacy hubs with harmonised transport rules for short-lived isotopes, and a global isotope supply observatory that forecasts shortages before they happen.","refs":["idea-reg-yb176-enrichment-capacity","idea-reg-medical-isotope-reactor-reserve","idea-reg-regional-radiopharmacy-hubs","idea-reg-isotope-supply-observatory","idea-reg-legacy-radium-recovery-ac225"],"status":"speculative"}],"watch":[{"item":"NorthStar RadioGenix expansion and additional Mo-99 filling lines","expected":"FDA approval of two additional Mo-99 filling lines, announced 18 February 2020","source":"https://www.itnonline.com/content/fda-approves-additional-molybdenum-99-mo-99-filling-lines-northstar-medical-radioisotopes","refs":["northstar-medical-radioisotopes"]},{"item":"TerraPower Isotopes' Philadelphia cGMP actinium-225 facility begins production","expected":"Production of cGMP actinium-225 beginning in 2029","source":"https://www.terrapower.com/TerraPower-Isotopes-announces-cGMP-manufacturing-facility","refs":["terrapower-isotopes"]}]},"route":"/roadmaps/isotope-supply-roadmap/","neighbours":{"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"},{"id":"mo-99","kind":"isotope","name":"Molybdenum-99","route":"/isotopes/mo-99/"},{"id":"tc-99m","kind":"isotope","name":"Technetium-99m","route":"/isotopes/tc-99m/"}],"technology":[{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/"},{"id":"cyclotron-isotope-production","kind":"technology","name":"Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)","route":"/technologies/cyclotron-isotope-production/"},{"id":"radiopharmacy-network","kind":"technology","name":"Radiopharmacy and cyclotron networks","route":"/technologies/radiopharmacy-network/"},{"id":"research-reactor-isotope-production","kind":"technology","name":"Research reactors for medical isotopes (Mo-99, Lu-177, I-131)","route":"/technologies/research-reactor-isotope-production/"},{"id":"therapy-isotope-supply-chain","kind":"technology","name":"Therapeutic isotope supply chain (Mo-99, Lu-177, Ac-225)","route":"/technologies/therapy-isotope-supply-chain/"}],"company":[{"id":"ansto","kind":"company","name":"ANSTO (Australian Nuclear Science and Technology Organisation)","route":"/companies/ansto/"},{"id":"ire","kind":"company","name":"IRE (Institut national des Radioéléments)","route":"/companies/ire/"},{"id":"nordion","kind":"company","name":"Nordion (Sotera Health)","route":"/companies/nordion/"},{"id":"northstar-medical-radioisotopes","kind":"company","name":"NorthStar Medical Radioisotopes","route":"/companies/northstar-medical-radioisotopes/"},{"id":"ntp-radioisotopes","kind":"company","name":"NTP Radioisotopes","route":"/companies/ntp-radioisotopes/"},{"id":"nusano","kind":"company","name":"Nusano","route":"/companies/nusano/"},{"id":"orano-med","kind":"company","name":"Orano Med","route":"/companies/orano-med/"},{"id":"shine-technologies","kind":"company","name":"SHINE Technologies","route":"/companies/shine-technologies/"},{"id":"terrapower-isotopes","kind":"company","name":"TerraPower Isotopes","route":"/companies/terrapower-isotopes/"}],"drug":[{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"idea":[{"id":"idea-reg-medical-isotope-reactor-reserve","kind":"idea","name":"A coordinated reserve and shared schedule for the world's medical isotope reactors","route":"/ideas/idea-reg-medical-isotope-reactor-reserve/"},{"id":"idea-reg-isotope-supply-observatory","kind":"idea","name":"A global medical isotope supply observatory with forecasts and shortage alerts","route":"/ideas/idea-reg-isotope-supply-observatory/"},{"id":"idea-reg-yb176-enrichment-capacity","kind":"idea","name":"Build Western ytterbium-176 enrichment so lutetium-177 has more than one supplier","route":"/ideas/idea-reg-yb176-enrichment-capacity/"},{"id":"idea-reg-legacy-radium-recovery-ac225","kind":"idea","name":"Recover legacy radium-226 sources worldwide as the feedstock for actinium-225","route":"/ideas/idea-reg-legacy-radium-recovery-ac225/"},{"id":"idea-reg-regional-radiopharmacy-hubs","kind":"idea","name":"Regional radiopharmacy hubs and harmonised transport rules for short-lived isotopes","route":"/ideas/idea-reg-regional-radiopharmacy-hubs/"}]}}