Design of Bimodal Ligands of Neurotensin Receptor 1 for Positron Emission Tomography Imaging and Fluorescence-Guided Surgery of Pancreatic Cancer

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.