Neurotensin(8-13) analogue: radiolabeling and biological evaluation using different chelators

Introduction: Several strategies on the development of radiopharmaceuticals have been employed. Bifunctional chelators seem to be a promising approach since high radiochemical yields as well as good in vitro and in vivo stability have been achieved. To date, neurotensin analogs have been radiolabeled using the Tc-99m-carbonyl approach and none was described employing the bifunctional chelating agent technique. Aim: The purpose of this study was to evaluate the radiochemical and biological behaviour of NT(8-13) analogue radiolabeled with Tc-99m, using HYNIC and NHS-S-acetyl-MAG(3) as chelator agents. Methods: Radiolabeling, in vitro stability toward cysteine and glutathione, partition coefficient and plasma protein binding were assessed for both radioconjugates. Biodistribution in healthy Swiss mice were carried out in order to evaluate the biological behaviour of the radiocomplexes. Results: Radiochemical yields were higher than 97% and no apparent instability toward transchelant agents was observed for both radioconjugates. A higher lipophilic character was observed for the radioconjugate labeled via MAG(3). The chelators seem to have no effect on the percentage of the radioconjugate bound to plasma proteins. A similar biological pattern was observed for both radioconjugates. Total blood, bone and muscle values revealed a slightly slower clearance for the radiocomplex labeled via MAG(3). Moreover, a remarkable liver and intestinal uptake was observed for the radiocomplex labeled via MAG(3) even at the later time points studied. Conclusion: The high radiochemical yields achieved and the similar in vivo pattern found for both radioconjugates make them potential candidates for imaging tumors using nuclear medicine techniques. (C) 2011 Elsevier Inc. All rights reserved.