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

Abstract

Neurotensin receptors are overexpressed in several human tumors and can be targets for tumors diag- nosis and therapy. In this study, a new neurotensin ana- logue was labeled with 99m Tc via HYNIC and tricine/ EDDA as coligands and investigated further. (HYNIC 0 , Gly 7 ,L ys 9 , D-Tyr 11 )-Neurotensin (7-13) was synthesized using a standard Fmoc strategy. Labeling with 99m Tc was performed at 100 C for 10 min and radiochemical ana- lysis 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 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 correspond- ing to a specific activity of 81 MBq/nmol. Peptide conju- gate 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.