Targeted alpha therapy
Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage.
Actinium-225 and lead-212 agents (225Ac-PSMA-617, 225Ac-DOTATATE/RYZ101, 212Pb-DOTAMTATE/AlphaMedix, 225Ac-FAP) are in phase 3. Radium-223 (Xofigo) is the only approved alpha emitter, for bone metastases. Isotope supply (TerraPower, Orano, ITM) is the binding constraint. Alpha therapy after beta failure produces responses in PSMA-refractory disease.
How it works
Alpha particles (4-9 MeV, <100 µm range) cause clustered double-strand breaks independent of oxygen and cell cycle.
- Overcomes beta resistance
- Kills micrometastases with minimal crossfire
- Ac-225 supply
- Daughter-nuclide redistribution (salivary, renal toxicity)
- Dosimetry difficult
An alpha-particle version of neuroendocrine radioligand therapy that produced responses in over half of patients who had never had PRRT, with FDA Breakthrough designation.
An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version.
Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply.
Radium-223 was the first alpha-emitting drug ever approved (2013). It homes to bone like calcium and treats prostate cancer that has spread only to bone.
Latest papers
topQuery for this technology: (TITLE:"targeted alpha therapy" OR ABSTRACT:"targeted alpha therapy" OR TITLE:"actinium-225" OR ABSTRACT:"actinium-225" OR TITLE:"225Ac" OR ABSTRACT:"225Ac" OR TITLE:"lead-212" OR ABSTRACT:"lead-212" OR TITLE:"212Pb" OR ABSTRACT:"212Pb"). Results are unfiltered search hits about Targeted alpha therapy, not a curated reading list.
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