Design of Bimodal Ligands of Neurotensin Receptor 1 for PET Imaging and Fluorescence-Guided Surgery of Pancreatic Cancer.
Fiche publication
Date publication
décembre 2019
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck, Dr GONCALVES Victor
Tous les auteurs :
Renard E, Dancer PA, Portal C, Denat F, Prignon A, Goncalves V
Lien Pubmed
Résumé
Neurotensin receptor 1 (NTSR1) is overexpressed in most human pancreatic ductal adenocarcinomas. It makes it an attractive target for the development of pancreatic cancer imaging agents. In this study, we sought to develop a bimodal PET-fluorescent imaging agent capable of specifically targeting these receptors. Starting from the structure of a known NTSR1 agonist, a se-ries of tracers was synthesized, radiometalated with gallium-68 and evaluated in vitro and in vivo, in mice carrying an AsPC-1 xenograft. PET imaging allowed us to identify the compound [Ga]NODAGA-Lys(Cy5**)-AEEAc-[Me-Arg, Tle]-NT(7-13) as the one with the most promising biodistribution profile, characterized by high tumor uptake (2.56 ± 0.97 %ID/g, 1 h p.i.) and rapid elimination from non-targeted organs, through urinary excretion. Fluorescence imaging gave similar results. On this basis, fluorescence-guided resection of tumor masses was successfully carried out on a preclinical model.
Référence
J. Med. Chem.. 2019 Dec 19;: