{"entity":{"id":"ac-225","kind":"isotope","name":"Actinium-225","aka":["225Ac","Ac-225"],"tldr":"A metal that fires off very powerful, very short-range radioactive particles as it decays through a chain of daughter atoms. Because the particles barely travel beyond the cell they hit, it can kill a cancer cell while leaving neighbouring healthy cells mostly untouched. Supply is scarce, so it is still mostly used in research studies.","summary":"Actinium-225 decays by alpha emission through six short-lived daughters to stable bismuth-209, releasing a net four alpha particles per decay (a 'nanogenerator'). At 9.9 days its half-life is long enough for centralised manufacture and international shipping, unlike its short-lived daughter bismuth-213.\n\nThe historical route extracts 225Ac from decaying stockpiles of thorium-229 (itself from aged uranium-233), 'milked' every few weeks; the amounts are milligram/curie-scale and cannot be scaled much further. Newer accelerator routes -- proton spallation of thorium-232, or proton irradiation of radium-226 targets via 226Ra(p,2n)225Ac -- are being industrialised by the DOE's Tri-Lab effort (Brookhaven, Los Alamos, Oak Ridge) and by companies building cyclotron and linac capacity.\n\nSupply is the most contested number in the field. A 2023 Journal of Nuclear Medicine analysis put worldwide 229Th/225Ac-derived supply at roughly 63 GBq (1.7 Ci) per year, enough for only 100-200 patients, against a stated need for hundreds to thousands of curies a year if approved 225Ac drugs reach broad use; it projected accelerator and photonuclear routes could reach over 25 TBq (670 Ci) a year worldwide by 2032. Other DOE and IAEA figures from 2013-2021 cite current 229Th-derived supply at 1-2 Ci/year (37-74 GBq) split mainly between Oak Ridge National Laboratory (ORNL, USA), the Joint Research Centre in Karlsruhe (Germany, ~13 GBq/year) and IPPE Obninsk (Russia, ~22 GBq/year), and note the same production facilities co-produce the long-lived impurity 227Ac (half-life 21.8 years) at the 0.1-0.2% level, which complicates waste handling and dosimetry.","status":"phase-2","asOf":"2026-09-22","links":[{"label":"Is Actinium Really Happening? (Journal of Nuclear Medicine, 2023)","url":"https://jnm.snmjournals.org/content/64/10/1516"},{"label":"DOE Isotope Program: Production Methods for Ac-225","url":"https://www.isotopes.gov/information/actinium-225"},{"label":"Supply and Clinical Application of Actinium-225 and Bismuth-213 (PMC, 2020)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7082773/"},{"label":"Actinium-225 in targeted alpha-particle therapeutic applications (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5565267/"}],"tags":["therapy","alpha emitter","supply-constrained"],"related":["ac225-psma","ryz101","fpi-2265","targeted-alpha-therapy","actinium-225-supply","idea-reg-ac225-accelerator-pharmacopoeia","idea-reg-legacy-radium-recovery-ac225","bi-213"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"225Ac","element":"Actinium","massNumber":225,"halfLife":"9.92 days","emissions":["α 5.8 MeV (225Ac itself)","α, β and γ from the six-member decay chain to stable 209Bi (net 4 α, 3 β, 2 useful γ per decay)"],"emissionClass":"alpha","use":"therapy","tissueRange":"A few cell diameters (tens of micrometres)","production":"Decay of parent 229Th stockpiles ('milked' periodically), or accelerator: proton spallation of 232Th, or cyclotron 226Ra(p,2n)225Ac.","supply":"constrained","supplyNote":"Disputed. JNM (2023) estimated current 229Th-derived worldwide supply at ~63 GBq (1.7 Ci)/year, enough for 100-200 patients/year, versus a need in the hundreds-to-thousands of Ci/year for broad approval; it projected >25 TBq (670 Ci)/year of installed capacity worldwide by 2032 from accelerator and photonuclear routes. Earlier DOE/IAEA figures (2013-2021) put current 229Th/225Ac supply at roughly 1.2-1.7 Ci/year split between ORNL (USA), JRC Karlsruhe (Germany) and IPPE Obninsk (Russia).","chelators":["DOTA","macropa"],"pairedWith":["ga-68"]},"route":"/isotopes/ac-225/","neighbours":{"drug":[{"id":"aaa817","kind":"drug","name":"AAA817","route":"/drugs/aaa817/"},{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","route":"/drugs/ryz101/"},{"id":"ac-225-fpi-2068","kind":"drug","name":"Actinium-225 FPI-2068","route":"/drugs/ac-225-fpi-2068/"},{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/"},{"id":"fpi-2265","kind":"drug","name":"FPI-2265","route":"/drugs/fpi-2265/"}],"technology":[{"id":"actinium-225-supply","kind":"technology","name":"Actinium-225 supply: thorium stocks, accelerators and radium targets","route":"/technologies/actinium-225-supply/"},{"id":"alpha-daughter-redistribution","kind":"technology","name":"Alpha-emitter daughter redistribution ('free daughter' problem)","route":"/technologies/alpha-daughter-redistribution/"},{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","route":"/technologies/alpha-nanogenerators/"},{"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":"dota-chelation","kind":"technology","name":"DOTA chelation","route":"/technologies/dota-chelation/"},{"id":"hot-cells-and-shielding","kind":"technology","name":"Hot cells and radiation shielding","route":"/technologies/hot-cells-and-shielding/"},{"id":"macropa-chelation","kind":"technology","name":"Macropa chelation","route":"/technologies/macropa-chelation/"},{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","route":"/technologies/prrt/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"},{"id":"radiohybrid-chemistry","kind":"technology","name":"Radiohybrid (rh) chemistry","route":"/technologies/radiohybrid-chemistry/"},{"id":"radiolabelling-quality-control","kind":"technology","name":"Radiolabelling quality control","route":"/technologies/radiolabelling-quality-control/"},{"id":"radiopharmacy-network","kind":"technology","name":"Radiopharmacy and cyclotron networks","route":"/technologies/radiopharmacy-network/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"},{"id":"therapy-isotope-supply-chain","kind":"technology","name":"Therapeutic isotope supply chain (Mo-99, Lu-177, Ac-225)","route":"/technologies/therapy-isotope-supply-chain/"}],"idea":[{"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-fund-academic-radiopharma-pipeline","kind":"idea","name":"A university cyclotron network with shared regulatory files for new tracers","route":"/ideas/idea-fund-academic-radiopharma-pipeline/"},{"id":"idea-rlt-plus-parp-inhibitor","kind":"idea","name":"Adding a PARP inhibitor to PSMA radioligand therapy","route":"/ideas/idea-rlt-plus-parp-inhibitor/"},{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","route":"/ideas/idea-alpha-after-adc/"},{"id":"idea-alpha-first-mhspc","kind":"idea","name":"Alpha-emitting PSMA therapy at first metastatic diagnosis","route":"/ideas/idea-alpha-first-mhspc/"},{"id":"idea-alpha-for-oligometastatic-disease","kind":"idea","name":"Alpha-emitting PSMA therapy for oligometastatic (few-lesion) prostate cancer","route":"/ideas/idea-alpha-for-oligometastatic-disease/"},{"id":"idea-caix-theranostics","kind":"idea","name":"CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy","route":"/ideas/idea-caix-theranostics/"},{"id":"idea-reg-alpha-emitter-portfolio","kind":"idea","name":"Fund alpha emitters beyond actinium-225: lead-212, terbium-149 and astatine-211","route":"/ideas/idea-reg-alpha-emitter-portfolio/"},{"id":"idea-pretargeted-alpha-therapy","kind":"idea","name":"Pretargeted alpha radioimmunotherapy","route":"/ideas/idea-pretargeted-alpha-therapy/"},{"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-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/"},{"id":"idea-accelerator-ac225-at-scale","kind":"idea","name":"Scaling actinium-225 supply with proton accelerators instead of the thorium-229 cow","route":"/ideas/idea-accelerator-ac225-at-scale/"}],"isotope":[{"id":"bi-213","kind":"isotope","name":"Bismuth-213","route":"/isotopes/bi-213/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"},{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"},{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"},{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"company":[{"id":"actinium-pharmaceuticals","kind":"company","name":"Actinium Pharmaceuticals","route":"/companies/actinium-pharmaceuticals/"},{"id":"advancell","kind":"company","name":"AdvanCell","route":"/companies/advancell/"},{"id":"aktis-oncology","kind":"company","name":"Aktis Oncology","route":"/companies/aktis-oncology/"},{"id":"alpha-9-oncology","kind":"company","name":"Alpha-9 Oncology","route":"/companies/alpha-9-oncology/"},{"id":"ariceum-therapeutics","kind":"company","name":"Ariceum Therapeutics","route":"/companies/ariceum-therapeutics/"},{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"bwxt-medical","kind":"company","name":"BWXT Medical","route":"/companies/bwxt-medical/"},{"id":"cellbion","kind":"company","name":"CellBion","route":"/companies/cellbion/"},{"id":"convergent-therapeutics","kind":"company","name":"Convergent Therapeutics","route":"/companies/convergent-therapeutics/"},{"id":"eckert-ziegler","kind":"company","name":"Eckert & Ziegler","route":"/companies/eckert-ziegler/"},{"id":"evergreen-theragnostics","kind":"company","name":"Evergreen Theragnostics","route":"/companies/evergreen-theragnostics/"},{"id":"full-life-technologies","kind":"company","name":"Full-Life Technologies","route":"/companies/full-life-technologies/"},{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","route":"/companies/fusion-pharma/"},{"id":"iba","kind":"company","name":"IBA (Ion Beam Applications)","route":"/companies/iba/"},{"id":"ionetix","kind":"company","name":"IONETIX","route":"/companies/ionetix/"},{"id":"itm","kind":"company","name":"ITM Isotope Technologies Munich","route":"/companies/itm/"},{"id":"molecular-targeting-technologies","kind":"company","name":"Molecular Targeting Technologies","route":"/companies/molecular-targeting-technologies/"},{"id":"niowave","kind":"company","name":"Niowave","route":"/companies/niowave/"},{"id":"northstar-medical-radioisotopes","kind":"company","name":"NorthStar Medical Radioisotopes","route":"/companies/northstar-medical-radioisotopes/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"},{"id":"nusano","kind":"company","name":"Nusano","route":"/companies/nusano/"},{"id":"orano-med","kind":"company","name":"Orano Med","route":"/companies/orano-med/"},{"id":"ratio-therapeutics","kind":"company","name":"Ratio Therapeutics","route":"/companies/ratio-therapeutics/"},{"id":"rayzebio","kind":"company","name":"RayzeBio (BMS)","route":"/companies/rayzebio/"},{"id":"shine-technologies","kind":"company","name":"SHINE Technologies","route":"/companies/shine-technologies/"},{"id":"terrapower-isotopes","kind":"company","name":"TerraPower Isotopes","route":"/companies/terrapower-isotopes/"}],"institution":[{"id":"heidelberg-nct","kind":"institution","name":"Heidelberg University Hospital / NCT / DKFZ","route":"/institutions/heidelberg-nct/"},{"id":"kirams","kind":"institution","name":"Korea Institute of Radiological and Medical Sciences","route":"/institutions/kirams/"}],"term":[{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","route":"/terms/alpha-vs-beta/"},{"id":"biological-half-life","kind":"term","name":"Biological half-life","route":"/terms/biological-half-life/"},{"id":"chelator-term","kind":"term","name":"Chelator (bifunctional chelating agent)","route":"/terms/chelator-term/"},{"id":"half-life","kind":"term","name":"Half-life","route":"/terms/half-life/"},{"id":"prrt-term","kind":"term","name":"PRRT (peptide receptor radionuclide therapy)","route":"/terms/prrt-term/"},{"id":"psma-rads","kind":"term","name":"PSMA-RADS (PSMA reporting and data system)","route":"/terms/psma-rads/"},{"id":"radionuclidic-purity","kind":"term","name":"Radionuclidic purity","route":"/terms/radionuclidic-purity/"},{"id":"relative-biological-effectiveness","kind":"term","name":"Relative biological effectiveness (RBE)","route":"/terms/relative-biological-effectiveness/"},{"id":"theranostics","kind":"term","name":"Theranostics","route":"/terms/theranostics/"}],"trial":[{"id":"action-1","kind":"trial","name":"ACTION-1","route":"/trials/action-1/"},{"id":"alphabreak","kind":"trial","name":"AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","route":"/trials/alphabreak/"},{"id":"alsympca","kind":"trial","name":"ALSYMPCA","route":"/trials/alsympca/"},{"id":"nct07611110","kind":"trial","name":"AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)","route":"/trials/nct07611110/"},{"id":"nct06909825","kind":"trial","name":"FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)","route":"/trials/nct06909825/"},{"id":"nct07590934","kind":"trial","name":"Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer","route":"/trials/nct07590934/"},{"id":"nct06549465","kind":"trial","name":"Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer (CRPC)","route":"/trials/nct06549465/"},{"id":"nct06590857","kind":"trial","name":"Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.","route":"/trials/nct06590857/"}],"pairing":[{"id":"pluvicto-plus-olaparib","kind":"pairing","name":"177Lu-PSMA-617 (Pluvicto) with olaparib","route":"/pairings/pluvicto-plus-olaparib/"},{"id":"beta-psma-then-alpha-psma-rescue","kind":"pairing","name":"177Lu-PSMA-617 then 225Ac-PSMA rescue therapy","route":"/pairings/beta-psma-then-alpha-psma-rescue/"},{"id":"prrt-then-alpha-net","kind":"pairing","name":"Beta PRRT → alpha PRRT","route":"/pairings/prrt-then-alpha-net/"},{"id":"beta-then-alpha","kind":"pairing","name":"Beta radioligand → alpha radioligand","route":"/pairings/beta-then-alpha/"}],"roadmap":[{"id":"alpha-therapy-roadmap","kind":"roadmap","name":"Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline","route":"/roadmaps/alpha-therapy-roadmap/"},{"id":"isotope-supply-roadmap","kind":"roadmap","name":"Isotope supply roadmap: reactor dependence → non-uranium production → accelerator-made actinium","route":"/roadmaps/isotope-supply-roadmap/"},{"id":"neuro-imaging-roadmap","kind":"roadmap","name":"Neuro-oncology imaging roadmap: FDG PET → amino acid PET → SSTR2 theranostics in meningioma","route":"/roadmaps/neuro-imaging-roadmap/"},{"id":"psma-theranostics-roadmap","kind":"roadmap","name":"PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha","route":"/roadmaps/psma-theranostics-roadmap/"},{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/"},{"id":"sstr-theranostics-roadmap","kind":"roadmap","name":"SSTR theranostics roadmap: octreotide scintigraphy → 68Ga-DOTATATE → 177Lu-DOTATATE → alpha","route":"/roadmaps/sstr-theranostics-roadmap/"}],"person":[{"id":"clemens-kratochwil","kind":"person","name":"Clemens Kratochwil","route":"/people/clemens-kratochwil/"},{"id":"neeta-pandit-taskar","kind":"person","name":"Neeta Pandit-Taskar","route":"/people/neeta-pandit-taskar/"}],"bottleneck":[{"id":"b-ac225-supply","kind":"bottleneck","name":"Actinium-225 supply","route":"/bottlenecks/b-ac225-supply/"},{"id":"b-rlt-trial-capacity","kind":"bottleneck","name":"Clinical trial capacity for radioligand therapy","route":"/bottlenecks/b-rlt-trial-capacity/"},{"id":"b-dosimetry-standardisation","kind":"bottleneck","name":"Dosimetry standardisation for radioligand therapy","route":"/bottlenecks/b-dosimetry-standardisation/"},{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"journal":[{"id":"journal-of-nuclear-medicine","kind":"journal","name":"Journal of Nuclear Medicine","route":"/journals/journal-of-nuclear-medicine/"}],"collection":[{"id":"opendose","kind":"collection","name":"OpenDose","route":"/collections/opendose/"},{"id":"nrc-regulations-part35","kind":"collection","name":"US NRC 10 CFR Part 35 (Medical Use of Byproduct Material)","route":"/collections/nrc-regulations-part35/"}],"section":[{"id":"f-isotope-supply","kind":"section","name":"Isotope supply","route":"/fronts/f-isotope-supply/"},{"id":"f-alpha-therapy","kind":"section","name":"Targeted alpha therapy","route":"/fronts/f-alpha-therapy/"}],"paper":[{"id":"paper-kratochwil-ac225-psma-jnm-2016","kind":"paper","name":"225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer","route":"/key-papers/paper-kratochwil-ac225-psma-jnm-2016/"},{"id":"paper-tagawa-ac225-j591-jco-2024","kind":"paper","name":"Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC","route":"/key-papers/paper-tagawa-ac225-j591-jco-2024/"},{"id":"paper-sgouros-tat-review-nat-rev-2020","kind":"paper","name":"Radiopharmaceutical therapy in cancer: clinical advances and challenges","route":"/key-papers/paper-sgouros-tat-review-nat-rev-2020/"}]}}