A Practical Guide to PSMA PET Radiopharmaceuticals for Prostate Cancer Imaging, From the AJR Special Series on Molecular Imaging.

Abstract

Since the first FDA approval of a PSMA-targeted PET radiopharmaceutical ([⁶⁸Ga]Ga-PSMA-11) in 2020, PSMA PET/CT has rapidly become the standard of care for certain indications in prostate cancer imaging. Subsequently, the FDA also approved [¹⁸F]DCFPyl and [¹⁸F]rhPSMA-7.3. Although these small-molecule agents share an amino acid binding domain specific to the PSMA molecule, they differ in key ways (e.g., radioisotope physical and chemical properties, ligand structure), with potential clinical implications regarding synthesis, distribution, and imaging characteristics. For example, differences in radiopharmaceutical clearance (predominantly renal vs hepatic) may impact the detection of lesions adjacent to the urinary tract or within the liver. This variability also influences pre-therapy assessment, during which lesion uptake is often compared to the liver as a reference. Direct intrapatient comparisons among PSMA-targeted radiopharmaceuticals remain limited, and current evidence suggests lack of overall superiority in diagnostic performance metrics for any individual radiopharmaceutical. Consequently, radiologists are left wondering why multiple PSMA-targeted radiopharmaceuticals are being developed, whether their distinct properties matter clinically, and ultimately which one to use. In this article, we explore clinically relevant similarities and differences of PSMA-targeted PET radiopharmaceuticals, highlighting their imaging characteristics, supply logistics, and other operational considerations, to guide their successful integration into clinical care.