A straightforward method to enhance water solubility of fluorescent organic dyes (cyanines and rhodamines) by a postsynthetic chemical derivatization of their carboxylic acid functionality with an original disulfonated heterobifunctional linker is described. Significant water solubility enhancement is achieved without compromising either the photophysical properties (especially large molar extinction coefficients and high quantum yields) or bioconjugation efficiency of the parent non-water-soluble fluorophores. The results both demonstrate the strong potential of these new compounds as fluorescent labels for a broad range of biotechnology and biomedical applications and illustrate the utility of such an easy-to-handle water-solubizing group.

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 series of tracers was 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 [ 68 Ga]Ga-NODAGA-Lys(Cy5**)-AEEAc-[Me-Arg 8 , Tle 12 ]-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.