Actinium-225
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.
Overview
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.
The 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.
Supply 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.
- 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)
- DOTA
- macropa
Theranostic partners
- Gallium-68 · A radioactive metal with a one-hour lifetime that is eluted from a shielded generator or made on a cyclotron and attached to a molecule that finds tumours, giving a PET scan the same day.
AAA817 is an experimental radioligand therapy from Novartis Pharmaceuticals in phase 3 trials for prostate cancer, aimed at PSMA.
An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version.
An antibody engineered to grab onto two markers found together on some solid tumours, but not on healthy cells, carries a powerful short-range radioactive payload into the tumour to try to destroy it.
Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply.
FPI-2265 is an experimental radioligand therapy from Fusion Pharmaceuticals in phase 2 trials for prostate cancer, aimed at PSMA.
An alpha-emitting radioactive drug built on a PSMA-targeting antibody, rather than the small-molecule ligands used in existing PSMA therapies, was safe enough to move into further testing and shrank PSA in roughly a third to a half of heavily pre-treated men, including some whose cancer had already stopped responding to lutetium-177 PSMA therapy.
This paper is a map of the radioactive-cancer-drug field at a pivotal moment, explaining to non-specialists and drug developers alike why these treatments work differently from chemotherapy and what needed to be fixed - supply, dosing science, regulation - before more of them could reach patients.
This was the first evidence, in two patients, that attaching a more powerful (alpha-emitting) form of radiation to the same PSMA-seeking molecule used in lutetium-177 PSMA therapy could produce a complete response even in prostate cancer that had already stopped responding to the beta-emitter version.
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