PSMA Theranostics in Prostate Cancer: From Standardized PET Imaging to Clinical Implementation of Radioligand Therapy

Prostate-specific membrane antigen (PSMA) has become a central molecular target in prostate cancer because it enables both high-performance imaging and targeted radioligand therapy. PSMA positron emission tomography/computed tomography (PET/CT) is now used across several clinical settings, including primary staging of higher-risk localized disease, localization of biochemical recurrence, salvage radiotherapy planning, and assessment of oligometastatic disease. In metastatic castration-resistant prostate cancer, PSMA-targeted radioligand therapy (RLT), particularly lutetium-177-labeled PSMA-617, has established therapeutic value and is moving into earlier disease states. From an applied science perspective, the clinical performance of PSMA theranostics depends not only on target expression and trial efficacy, but also on radiopharmaceutical design, radionuclide selection, radiochemical quality, PET acquisition and reconstruction, standardized reporting, dosimetry, and quantitative response assessment. This narrative review summarizes the biological, radiochemical, and technical foundations of PSMA theranostics, the clinical evidence supporting PSMA PET/CT in key disease states, and the pivotal data for PSMA-targeted RLT. It also discusses imaging-based treatment eligibility, dosimetry, post-therapy imaging, Response Evaluation Criteria in PSMA Imaging, and next-generation beta- and alpha-emitting platforms. PSMA theranostics should be understood as an integrated clinical and technological platform that links molecular imaging, treatment selection, radionuclide delivery, and longitudinal response assessment across the prostate cancer care pathway.