Preparation and preclinical evaluation of 68 Ga-iPSMA-BN as a potential heterodimeric radiotracer for PET-imaging of prostate cancer

In this research, we report the labeling and preclinical evaluation of the heterodimer 68 Ga-iPSMA-BN ligand regarding its ability to target the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) in prostate cancer tumors. A heterodimer conjugate of iPSMA (PSMA inhibitor) (Nal-Lys-CO-Glu-OH) and Lys 3 -Bombesin (BN) with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as chelator was synthesized, labeled with 68 Ga and the in vitro PSMA/GRPr affinity assessed. Using pulmonary micrometastasis LNCaP (PSMA+) and PC3 (GRPr+) models, the influence of the ligand heterobivalency and affinity on the tumor uptake was analyzed quantitatively from the micro-PET imaging data, obtaining promising results.