# Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer

## TL;DR

This review discusses how prostate-specific membrane antigen (PSMA) is being used to improve the diagnosis and treatment of prostate cancer through targeted imaging and therapies.

## Contribution

The paper provides a comprehensive and critical overview of recent advancements in PSMA-based precision diagnosis and treatment strategies for prostate cancer.

## Key findings

- PSMA PET/CT imaging with radionuclides improves tumor staging and detection of recurrent lesions.
- Radioligand therapies like 177Lu-PSMA-617 and 225Ac-PSMA-617 have shown survival benefits in clinical trials.
- PSMA-targeted therapies including antibodies, ADCs, and CAR-T are being optimized for personalized treatment.

## Abstract

Prostate cancer (PCa) is the most common malignant tumor of the male genitourinary system, and its incidence and mortality have shown a marked global increase in recent years. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein highly expressed in PCa cells, has emerged as a vital molecular target in the field of PCa precision diagnosis and therapy. In recent years, significant advances have been achieved in PSMA-based molecular imaging, radioligand therapy, and the development of novel targeted drugs. This review aims to summarize and critically discuss recent advances in PSMA-targeted molecular imaging, radioligand therapy, and emerging therapeutic strategies, highlighting their roles in precision diagnosis and personalized treatment of PCa. PSMA positron emission tomography/computed tomography (PET/CT) imaging using radionuclides such as 68Ga and 18F has markedly improved the accuracy of primary tumor staging, localization of recurrent lesions, and therapeutic response assessment. Radioligand therapies, such as 177Lu-PSMA-617 and 225Ac-PSMA-617, have prolonged survival and demonstrated symptomatic benefits in multiple clinical trials, and are now applied in early disease stages, including chemotherapy-naïve and hormone-sensitive settings. Meanwhile, PSMA-targeted antibodies and antibody–drug conjugates (PSMA-ADCs), as well as bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, are constantly being optimized and show promising clinical potential. Furthermore, PSMA-targeted nanoplatforms enable precise delivery of chemotherapeutic agents, photosensitizers, or imaging probes, achieving integrated diagnosis and therapy with multimodal imaging guidance, and offering new strategies for individualized treatment. Taken together, the evidence summarized in this review highlights PSMA as a pivotal molecular target supporting precision diagnosis and personalized treatment across the continuum of prostate cancer management.