Hybrid Bombesin Analogues: Combining an Agonist and an Antagonist in Defined Distances for Optimized Tumor Targeting

Radiolabeled hybrid ligands with defined distances between an agonist and an antagonist for the gastrin-releasing peptide receptor were found to have excellent tumor-targeting properties. Oligoprolines served as rigid scaffolds that allowed for tailoring distances of 10, 20, and 30 angstrom between the recognition elements. In vitro and in vivo studies revealed that the hybrid ligand with a distance of 20 angstrom between the recognition elements exhibits the highest yet observed tumor cell uptake and retention time in prostate cancer cells.