Preclinical evaluation of a new technetium-99m labeled neurotensin analogue for NTSR1 targeted radionuclide imaging

Neurotensin is a regulatory peptide that can act as a growth factor on different types of normal and cancerous cells. Binding of Neurotensin to relevant receptors leads to cell proliferation, survival, migration and invasion by changing intracellular enzyme activity. Therefore, the design of a neurotensin-based radiopeptide plays an important role in targeted imaging or therapy of neurotensin receptor-positive tumors. A [Lys⁸]-neurotensin (7-13) peptide was synthesized and attached to HYNIC as a chelator via a linker. The labeling procedure was carried out at 100 °C for 10 min using ^99mTc as a radionuclide and EDDA/tricine as coligands. Stability of the labeled peptide in human serum was determined using RTLC and HPLC methods. The receptor binding internalization was studied using HT-29 colon carcinoma cells, and tissue biodistribution was evaluated in mice bearing CT-26 tumors. The [^99mTc]Tc-Tricine/EDDA/HYNIC-GABA-[Lys⁸]-neurotensin (7-13) peptide demonstrated a labeling yield of over 98 %, a specific activity of 37.00 GBq/µmol, high stability in human serum, a nanomolar range of K_d, and a tumor uptake of 0.36 ± 0.15 % ID/g at 1-h post-injection. These results suggest that the labeled peptide is a suitable imaging agent for neurotensin receptor-positive tumors.