Rien Ritawidya
1,2 
, Hendris Wongso
1,2 , Nurmaya Effendi
3 , Anung Pujiyanto
1, Wening Lestari
1 , Herlan Setiawan
1 , Titis Sekar Humani
1* 1 Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, National Research and Innovation Agency (BRIN), Kawasan Puspiptek, Setu, Tangerang Selatan, 15314 Indonesia.
2 Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia.
3 Faculty of Pharmacy, University of Muslim Indonesia, Kampus II UMI, Jl. Urip Sumoharjo No.225, Panaikang, Panakkukang, Kota, Makassar, Sulawesi Selatan 90231.
Abstract
Prostate-specific membrane antigen (PSMA) represents a promising target for PSMA-overexpressing diseases, especially prostate cancer-a common type of cancer among men worldwide. In response to the challenges in tackling prostate cancers, several promising PSMA inhibitors from a variety of molecular scaffolds (e.g., phosphorous-, thiol-, and urea-based molecules) have been developed. In addition, PSMA inhibitors bearing macrocyclic chelators have attracted interest due to their favorable pharmacokinetic properties. Recently, conjugating a small PSMA molecule inhibitor-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, as exemplified by [177Lu]Lu-PSMA-617 could serve as a molecular imaging probe and targeted radioligand therapy (TRT) of metastatic castration resistant prostate cancer (mCRPC). Hence, studies related to mCRPC have drawn global attention. In this review, the recent development of PSMA ligand-617-labeled with 177Lu for the management of mCRPC is presented. Its molecular mechanism of action, safety, efficacy, and future direction are also described.