New 68Ga Glu-Urea-Lys(Ahx)-HBED-CC Derivatives as Prostate Specific Membrane Antigen (PSMA) Imaging Agents.

1366 Objectives Recently, successful PET/CT imaging studies of tumor targeting prostate-specific membrane antigen (PSMA) using 68Ga-Glu-NH-CO-NH-Lys(Ahx)-HBED-CC, [68Ga]1a, (PSMA-11) has demonstrated great potential for clinical diagnosis of prostate cancer. Successful imaging studies using [68Ga]1a, in humans have been widely reported. Methods A series of 68Ga labeled Glu-NH-CO-NH-Lys(Ahx) amide derivatives have been prepared including HBED-CC derivative containing various amino acids, 2-glucosamine and DOTA (1b-f),were prepared. Results The “cold” ligands, 1a-f displayed very good binding affinities (IC50 = 3 -35 nM) to the PSMA binding sites (in vitro binding assay with membrane homogenates of LnCAP cells over expressing PSMA). The new ligands, 1b-g, were labeled with [68Ga]GaCl3 with high yields and excellent radiochemical purity (> 99%). Results of in vivo biodistribution studies in mice after an iv injection of [68Ga]1b-f suggested that they are specifically localized in xenographed LnCAP tumor express the PSMA binding sites. In vivo microPET imaging studies in the same xenographed tumor also indicated that these agents highly concentrated in the tumor after an iv injection. Results suggested that new derivatives, [68Ga]1b-f, displayed PSMA binding properties comparable to that of [68Ga]1a. Conclusions New PSMA tracers, [68Ga]1b-f, are potentially useful as imaging agents for detecting PSMA expression in tumor tissues. They would provide practical in vivo PSMA imaging agents in conjunction with PET without the need of a near-by cyclotron.