212Pb-PSMA-617

212Pb-PSMA-617 is an investigational targeted alpha-particle radioligand therapy being evaluated for the treatment of advanced prostate cancer, specifically metastatic castration-resistant prostate cancer (mCRPC). It consists of the small-molecule prostate-specific membrane antigen (PSMA)-targeting ligand PSMA-617 labeled with the alpha-emitting radionuclide lead-212 (212Pb). PSMA-617 binds with high affinity to PSMA (glutamate carboxypeptidase 2), which is highly overexpressed on prostate cancer cells. Upon binding, the radioligand is internalized into the tumor cells. Lead-212 acts as an in vivo generator, decaying with a half-life of 10.6 hours to bismuth-212 (212Bi), which subsequently emits high-energy alpha particles. These alpha particles deliver dense ionizing radiation over a very short range (50–100 µm), causing double-stranded DNA breaks and potent tumor cell killing while minimizing damage to surrounding healthy tissues. Preclinical studies, including those conducted at the University of Chicago, have demonstrated that 212Pb-PSMA-617 exhibits high tumor uptake, rapid internalization, and potent in vitro cytotoxicity, offering a promising alternative to beta-emitting therapies like 177Lu-PSMA-617 (Pluvicto).

Other names

212Pb-labeled PSMA-617lead-212 PSMA-617lead212 PSMA-617lead 212 PSMA-617[212Pb]Pb-PSMA-617