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terbium (161Tb) zadavotide guraxetan (also known as 161Tb-PSMA-1 or 161Tb-PSMA-I&T) is an investigational next-generation targeted radioligand therapy (RLT) consisting of the prostate-specific membrane antigen (PSMA)-targeting peptidomimetic ligand zadavotide guraxetan (PSMA-I&T) radiolabeled with the therapeutic radionuclide terbium-161 (161Tb). Terbium-161 is a unique lanthanide isotope that decays via beta-minus emission, similar to lutetium-177, but additionally emits a high abundance of low-energy conversion and Auger electrons. These short-range, high-linear energy transfer (LET) electrons deposit dense radiation energy over nanometer-to-micrometer distances, enabling highly localized cytotoxicity that is particularly effective at eradicating single cancer cells and micrometastatic deposits while sparing surrounding healthy tissues. 161Tb-PSMA-1 is being clinically evaluated in Phase I/II trials for the treatment of PSMA-positive metastatic clear cell renal cell carcinoma (mccRCC) and metastatic castration-resistant prostate cancer (mCRPC).
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