Preparation and Preliminary Evaluation of Neurotensin Radiolabelled with 68Ga and 177Lu as Potential Theranostic Agent for Colon Cancer

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of Ga-68-DOTA-NT and Lu-177-DOTA-NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for Ga-68-DOTA-NT and 48 h for Lu-177-DOTA-NT. Extensive in vitro studies were conducted to assess the uptake and retention of Ga-68-DOTA-NT, the amount of non-specific binding of neurotensin and the effect of Lu-177-DOTA-NT on HT-29 cells. In vivo biodistribution of Ga-68-DOTA-NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. Lu-177-DOTA-NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic Ga-68/Lu-177 radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.

Automated summary

This study aimed to demonstrate the ability of radiolabeled neurotensin to target colon cancer cells specifically and substantiate its usefulness in targeted imaging and radiotherapy. The syntheses of Ga-68-DOTA-NT and Lu-177-DOTA-NT showed high purity and stability, indicating the potential of neurotensin in delivering imaging/therapeutic Ga-68/Lu-177 radioisotopes pair. Further evaluation is needed to assess the possible radiotoxicity effects on the liver, kidneys, or bone marrow.