Synthesis and evaluation of a new bombesin analog labeled with 99mTc as a GRP receptor imaging agent

Abstract

Tumors such as prostate, small cell lung cancer, breast, gastric and colon cancer are known to overexpress receptors to bombesin (BBN). In this study, a new bombesin analogue was labeled with 99mTc via HYNIC and tricine/EDDA as coligands and investigated further. HYNIC-GABA-Bombesin (7–14) NH2 was synthesized using a standard Fmoc strategy. Labeling with 99mTc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of humane serum at 37 °C up to 24 h. The receptor bound internalization and externalization rates were studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in nude mice bearing PC-3 tumor. Labeling yield of >98% was obtained corresponding to a specific activity of ~2.6 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed high and specific internalization into PC-3 cells (14.63 ± 0.41% at 4 h). In biodistribution studies, a receptor-specific uptake was observed in GRP-receptor-positive organs so that after 4 h the uptakes in mouse tumor and pancreas were 1.31 ± 0.18 and 1.2 ± 0.13% ID/g, respectively.