The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer

Abstract

The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors ¹²³I-MIP-1972 and ¹²³I-MIP-1095. A clinical breakthrough followed in 2011 with ⁶⁸Ga-PSMA-11 for PET imaging and ¹³¹I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with ⁶⁸Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. ⁶⁸Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, ¹³¹I-related PSMA therapy has been replaced by ¹⁷⁷Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is ^99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.