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

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.