Preparation and evaluation of a new neurotensin analog labeled with 99mTc for targeted imaging of neurotensin receptor positive tumors

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 Tc-99m 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 Tc-99m was performed at 100 A degrees 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 A degrees C 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 +/- A 0.54 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed specific internalization into HT-29 cells (12.43 +/- A 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 +/- A 0.16 and 0.63 +/- A 0.12 % ID/g respectively.