New neurotensin analogue radiolabeled by 99m‐technetium as a potential agent for tumor identification

It has been shown that more than 75% of ductal pancreatic adenocarcinomas overexpressed neurotensin (NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non‐invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor‐positive tumors such as pancreatic carcinoma. Radiolabeling was performed at 95°C for 10 min using 99mTc in the presence of tricine/EDDA exchange labeling. Radiochemical yield analysis involved ITLC and HPLC methods. A binding assay test was carried out in nine different concentrations of labeled neurotensin analogues in HT‐29 cells. Radiopeptide‐specific binding and internalization were studied in NT receptors expressing HT‐29 cells. Biodistribution studies were performed in tumor‐free BALB/c mice and HT‐29 xenografted tumor‐bearing nude mice. The peptide was efficiently labeled by 99mTc with high radiochemical yields (>98%). The radioconjugate was thoroughly stable in the solution and human serum even for 24 hr. The radiolabeled peptide showed high affinity (32.66 ± 4.01 nm) and specificity internalization (>%18 after 4 hr) to HT‐29 cells. The radiopeptide efficiently showed tumor size and location in tumor‐bearing nude mice. In biodistribution, a receptor‐specific uptake of radiopeptide was observed in neurotensin receptor‐positive organs such as intestine. Uptake in the tumor was 4.59 ± 0.23% ID/g after 2 hr. Owing to excellent stability, high affinity, rapid blood clearance, low accumulation in non‐target organs, and high uptake in tumor, the 99mTc–HYNIC‐peptide is a potential agent for targeting of NTR‐overexpressing tumor cells in clinical surroundings. When successfully executed in the clinical surrounding, non‐invasive imaging of NTR‐positive tumors with 99mTc‐labeled new neurotensin analogues could facilitate therapy procedure and monitoring.