LAUSR

Abstract The majority of aggressive prostate cancers overexpress the transmembrane protein prostate-specific membrane antigen (PSMA). PSMA is, therefore, an attractive target for drug development. Over the last decade, numerous PSMA-targeted radiopharmaceuticals for imaging and therapy have been developed and investigated in theranostic combination. PSMA-targeted radiopharmaceuticals for imaging have been primarily developed for PET. PSMA PET provides whole-body evaluation of the degree of PSMA expression on tumors and potentially provides a method to better select patients for PSMA-targeted therapy. Numerous PSMA-targeted therapeutic agents using β- or α-particle emitters are under study in clinical trials. In particular, the β-particle–emitting radioisotope 177Lu bound to PSMA-targeted small molecules have ongoing and completed late-stage clinical trials in metastatic castration-resistant prostate cancer. To define the most appropriate patient group for PSMA-targeted therapeutics, multiple studies have investigated PSMA and FDG PET/CT to establish PET parameters as predictive and prognostic biomarkers. This article discusses recent clinical trials that examine the optimal use of PET for the selection of patients for PSMA-targeted therapeutics and provides an integrative overview of choice of PET tracer(s), targeting molecule, therapeutic radioisotope, nonradioactive therapy, and cancer type (prostate or nonprostate).