Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study.

Four open chain tetraamine-functionalized bombesin (BB) analogues were synthesized [parent tetradecapeptide-based Demobesin 3 and 4 and BB(7-14)-based Demobesin 5 and 6]. Labeling with (99m)Tc afforded high-purity and high specific activity radiotracers. Peptides showed high affinity for the human GRP-R (GRP-R = gastrin releasing peptide receptor) expressed in PC-3 cells. In human tumors preferentially expressing single bombesin receptor subtypes, they showed high affinity for the GRP-R, less affinity for the NMB-R (NMB-R = neuromedin B receptor) and no affinity for the orphan BB(3)-R (bombesin subtype 3 receptor). [(99m)Tc]Demobesin 3-6 efficiently internalized in a time- and dose-dependent manner in PC-3 cells and showed a high and specific uptake in human PC-3 xenografts and the pancreas of nude mice. [(99m)Tc]Demobesin 3 and 4 were rapidly excreted via the kidneys while the truncated analogues were predominantly processed by the hepatobiliary system. Patient studies are scheduled for validating the suitability of [(99m)Tc]Demobesin 3 and 4 in the GRP-R-targeted imaging of tumors.