Fiche publication
Date publication
juin 2021
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck
,
Dr GONCALVES Victor
,
Dr COLLIN Bertrand
,
Dr BELLAYE Pierre-Simon
Tous les auteurs :
Renard E, Moreau M, Bellaye PS, Guillemin M, Collin B, Prignon A, Denat F, Goncalves V
Lien Pubmed
Résumé
Neurotensin receptor 1 (NTS) is involved in the development and progression of numerous cancers, which makes it an interesting target for the development of diagnostic and therapeutic agents. A small molecule NTS antagonist, named [Lu]Lu-IPN01087, is currently evaluated in phase I/II clinical trials for the targeted therapy of neurotensin receptor-positive cancers. In this study, we synthesized seven compounds based on the structure of NTS antagonists, bearing different chelating agents, and radiolabeled them with gallium-68 for PET imaging. These compounds were evaluated and in mice bearing a HT-29 xenograft. The compound [Ga]Ga-bisNODAGA- showed a promising biodistribution profile with mainly signal in tumor (4.917 ± 0.776%ID/g, 2 h post-injection). Its rapid clearance from healthy tissues led to high tumor-to-organ ratios, resulting in highly contrasted PET images. These results were confirmed on subcutaneous xenografts of AsPC-1 tumor cells, a model of NTS-positive human pancreatic adenocarcinoma.
Référence
J Med Chem. 2021 Jun 9;:
