Preparation of a labeled neurotensin analog and its biological evaluation for tumor imaging

Aim and The biological actions of the peptides are mediated upon binding with high affinity to specific receptors. Neurotensin is a tridecapeptide localized in central nervous system and in peripheral tissues. Three different receptor subtypes have been described for it among which the first one showing high affinity binding for NT was observed in ductal pancreatic adenocarcinoma. Since pancreas carcinoma is among the most frequent causes of cancer deaths، the need to use new radiopharmaceuticals which are able to diagnose cancer in the early steps is evident. A neurotensin analogue modified at the N-terminus by tetramine was obtained by solid phase peptide synthesis technique and s tandard fmoc strategy. Peptide conjugate was radiolabeled with 99mTc and s tability was tested in vitro in saline and human serum. Binding and internalization studies were carried out in neurotensin receptor expressing HT-29 cells. In vivo distribution studies were performed in normal mice. The radiolabeled complex prepared at high specific activities and >90% radiochemical yield. Peptide conjugate showed specific binding to neurotensin receptors. The radioligand showed high and specific internalization into HT-29 cells (22% at 4 h). In vivo distribution studies in mice have shown a low uptake of radioactivity in organs، such as the blood، bone، spleen، pancreas and muscle at 4 h post injection. A high uptake was found in the intestine، colon and kidneys. D ata show that this new labeled analogue exhibits favorable biodistribution pattern and is a specific radioligand for diagnostic of neurotensin receptor positive tumors.