Preparation and evaluation of a new neurotensin analog labeled with ~(99m)Tc for targeted imaging of neurotensin receptor positive tumors

摘要

Neurotensin receptors are overexpressed in several human tumors and can be targets for tumors diagnosis and therapy. In this study, a new neurotensin analogue was labeled with ~(99m)Tc via HYNIC and tricine/ EDDA as coligands and investigated further. [HYNIC0, Gly~7, Lys~9, D-Tyr~(11)]-Neurotensin (7–13) was synthesized using a standard Fmoc strategy. Labeling with ~(99m)Tc was performed at 100 ℃ 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 ℃ up to 24 h. The receptor bound internalization and externalization rates were studied in neurotensin receptor expressing HT-29 cells. Biodistribution of radiopeptide was studied in nude mice bearing HT-29 tumor. Labeling yield of 98.6 ± 0.54 % (n = 3) was obtained corresponding to a specific activity of 81 MBqmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed specific internalization into HT-29 cells (12.43 ± 0.52 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in neurotensin receptor positive organs so that after 1 h the uptakes in mouse intestine and tumor were 0.87 ± 0.16 and 0.63 ± 0.12 % ID/g respectively.