Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties.

Investigate the impact of various halogens on pharmacokinetics, biodistribution, and micro positron emission tomography/computed tomography (PET/CT) imaging of Glu-urea-Lys-based prostate-specific membrane antigen (PSMA) inhibitors. Based on the modification of SC691, a small molecule inhibitor of PSMA previously developed by our group, we synthesized 68Ga-labeled compounds by modifying the lysine terminal amino with different halogenated phenyl substituents. After complete characterization, in vitro and in vivo properties were studied. The [68Ga]Ga-DOTA-SC691-R possesses a high radiochemical yield (98–99