Recent Progress of Functionalized PSMA in Radionuclide Targeted Therapy for Prostate Cancer

Prostate cancer (PCa) is the most common malignant tumor in the male reproductive system. Prostate specific membrane antigen (PSMA) is an effective target for the diagnosis and treatment of prostate cancer. The anti-PSMA small molecule/polypeptide/monoclonal antibody labeled with the therapeutic nuclides ¹⁷⁷Lu/⁹⁰Y has shown important anti-tumor activity, but it also produces specific uptake of glands, bone marrow and kidneys, which leads to normal organs' damage. In addition, small molecules/peptides are easy to be cleared by the circulatory system. Radionuclide targeted therapy based on small molecules/peptides often requires high doses or frequent administration, which leads to unpredictable organ toxicity while inhibiting tumors. Radionuclide targeted therapy relies on the delivery of radionuclides to tumor-expressed receptors, but the binding capacity of ligands to receptors is limited. In order to improve the use efficiency of radionuclides, prolong the metabolism of radionuclide therapeutic PSMA molecular probes as well as increase the ratio of target to non target, great progress has been made in the study of functional modification of PSMA molecular probes which can improve the pharmacokinetic behavior. In this paper, we summarize the recent clinical translation and clinical research of functional nuclide targeting PSMA molecular probe in the treatment of prostate cancer.