New Neurotensin analogue radiolabeled by 99mTechnetium as a potential agent for tumor identification

Abstract

Introduction

It has been shown that more than 75% of ductal pancreatic adenocarcinomas are overexpress 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.

Methods

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.

Result

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 h. The radiolabeled peptide showed high affinity (32.66 ±4.01 nM) and specificity internalization (>%18 after 4 h) 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 h.

Conclusion

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.

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Radiochemical purity of radiopeptide was high .Radiopeptide showed high affinity, specificity internalization to HT-29 cells and it efficiently showed tumor size and location in tumor-bearing nude mice. In biodistribution, receptor-specific uptake of radiopeptide was observed in neurotensin receptor-positive organs such as tumor and intestine.

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