PSMA Radioligands for Diagnostics and Treatment of Advanced Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is overexpressed in prostate cancer cells, with limited expression in benign and extraprostatic tissues. Based on these characteristics, several low-molecular-weight PSMA inhibitor radioligands have been developed for disease management strategies that integrate both therapeutic and diagnostic applications, collectively termed theranostics. Currently, four common diagnostic radiotracers include ^68^Ga-PSMA-11, ^18^F-DCFPyL, ^18^F-radiohybrid (rh)PSMA-7.3 and ^18^F-PSMA-1007, with the first three being approved by the U.S. Food and Drug Administration (FDA). Additionally, ^68^Ga-PSMA-11 and ^18^F-DCFPyL are also approved by the European Medicines Agency (EMA), while ^18^F-PSMA-1007 is approved on a country-by-country basis. PSMA-targeted radionuclide therapy is also a promising therapeutic option for men with prostate cancer. To date, ^177^Lu-PSMA-617 is the only PSMA-targeted radioligand therapy approved by both the FDA and EMA for clinical use. Emerging α-emitting therapies such as ^225^Ac-PSMA-617 are currently under clinical investigation and may provide additional benefit in patients with advanced or resistant disease. This review article provides a brief overview of available PSMA ligands for the diagnosis and treatment of advanced prostate cancer. PEER REVIEWED ARTICLE Received on June 06, 2025; accepted after peer review on October 13, 2025; published on October 15, 2025. **Peer reviewers:** Prof. Dr Oliver Sartor, Transformational Prostate Cancer Research Center, East Jefferson General Hospital, Metairie, Louisiana, USA One anonymous peer reviewer