Synthesis and characterization of a novel ⁶⁸Ga-labeled p-bromobenzyl lysine-urea-ODAP PSMA inhibitor

Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synthesized seven ODAP-Urea-Lys derivatives characterized with p-bromobenzyl group conjugated to lysine. The ligands showed medium-to-high potency, with K_i values ranging from 27.9 nM to 0.94 nM. The ligands could be efficiently radiolabeled with ⁶⁸Ga, in high purity. Radioligands were stable and showed PSMA specific cellular uptake, in PSMA⁺⁺ LNCaP cells and PSMA⁺ 22Rv1 cells over PSMA^- PC3 cells. MicroPET imaging was performed in 22Rv1 tumor-bearing mice and ⁶⁸Ga-ligand-1 showed the best characteristics among the seven ligands, with the highest tumor uptake (SUVmax: 0.56 ± 0.07). A biodistribution study was also performed. ODAP-Urea-Lys-p-bromobenzyl could be used to image prostate cancer in vivo, and the ligands could have high binding potency. The future investigation is still necessary to improve the tumor-specific uptake of this class of ligands and reducing the non-specific uptake in normal organs.