Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer

Simple Summary Imaging plays a crucial role in the accurate staging of prostate cancer. Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells, and targeting the PSMA protein for diagnostic purposes has become of great clinical value. Another valuable feature of PSMA is its opportunity to serve as a target for delivering radionuclide therapy to cancer cells. PSMA-ligands can be labeled with various radionuclides, such as alpha and beta-emitters. This review offers an overview of the literature on recent developments in nuclear medicine regarding PSMA in prostate cancer diagnostics and targeted radionuclide therapy. Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown superior detection rates compared to previous imaging modalities. Apart from targeting PSMA for diagnostic purposes, there is a growing interest in developing ligands to target the PSMA-protein for radioligand therapy (RLT). PSMA-based RLT is a novel treatment that couples a PSMA-antibody to (alpha or beta-emitting) radionuclide, such as Lutetium-177 (Lu-177), to deliver high radiation doses to tumor cells locally. Treatment with Lu-177-PSMA RLT has demonstrated a superior overall survival rate within randomized clinical trials as compared to routine clinical care in patients with metastatic castration-resistant prostate cancer (mCRPC). The current review provides an overview of the literature regarding recent developments in nuclear medicine related to PSMA-targeted PET imaging and Theranostics.