Design of Bimodal Ligands of Neurotensin Receptor 1 for Positron Emission Tomography Imaging and Fluorescence-Guided Surgery of Pancreatic Cancer.
J Med Chem
; 63(5): 2426-2433, 2020 03 12.
Article
en En
| MEDLINE
| ID: mdl-31855417
ABSTRACT
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 positron emission tomography (PET)/fluorescent imaging agent capable of specifically targeting these receptors. Starting from the structure of a known NTSR1 agonist, a series of tracers were synthesized, radiometalated with gallium-68, and evaluated in vitro and in vivo, in mice bearing an AsPC-1 xenograft. PET imaging allowed us to identify the compound [68Ga]Ga-NODAGA-Lys(Cy5**)-AEEAc-[Me-Arg8,Tle12]-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 post-injection) and rapid elimination from nontargeted 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Receptores de Neurotensina
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Colorantes Fluorescentes
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia