Comparison of Nuclear Medicine Therapeutics Targeting PSMA among Alpha-Emitting Nuclides

Abstract

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including 149Tb, 211At, 212/213Bi, 212Pb (for 212Bi), 223Ra, 225Ac, 226/227Th, and 230U, are known. However, some nuclides encounter problems with labeling methods and lack sufficient preclinical and clinical data. We labeled the compounds targeting prostate specific membrane antigen (PSMA) with 211At and 225Ac. PSMA is a molecule that has attracted attention as a theranostic target for prostate cancer, and several targeted radioligands have already shown therapeutic effects in patients. The results showed that 211At, which has a much shorter half-life, is no less cytotoxic than 225Ac. In 211At labeling, our group has also developed an original method (Shirakami Reaction). We have succeeded in obtaining a highly purified labeled product in a short timeframe using this method.

The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer

“…Although some reports showed a good PSA response, clinical experience is limited to retrospective observational studies, with no long-term data on progression-free survival (PFS) and OS [ 68 ]. In addition, the supply of [ 225 Ac]Ac-PSMA-617 is small and there have been concerns due to hematologic toxicity and xerostomia [ 69 , 70 ]. Phase I/II studies with [ 225 Ac]Ac-PSMA-617 (AcTION: NCT04597411) and [ 225 Ac]Ac-PSMA-617-I and -T (TATCIST: NCT05219500) are currently in course, and will provide more information on the therapeutic efficacy, safety, and dose-limiting toxicity [ 71 ].…”