Cyanine-based [F-18]F-C-glycosyl dual imaging probe: synthesis, physico-chemical characterization, in vitro binding evaluation and direct [F-18]fluorination

The design and synthesis of F-18-radiolabelled and fluorescent dual imaging agents allowing bimodal PET/FLI imaging is a current challenge. We report herein the development of a cyanine-based [F-18]F-C-glycosyl dual imaging probe for fluorescence imaging (FLI) and a robust [F-18]F-C bond for positron emission tomography (PET) imaging. Interestingly, the proposed strategy allows a late-stage coupling of the probe with various vectors, successfully illustrated by conjugation to c(RGDfK) via CuAAC for alpha(v)beta(3) integrin targeting. As attested by the in vitro evaluation, the novel dual agent demonstrates affinity for alpha(v)beta(3) integrins in the nanomolar range (IC50 = 398 nM). This fluorescent dual agent was fully characterized by photophysical measurements (lambda(abs)/lambda(em) = 643/660 nm, phi(fluo) = 0.13) and by NMR spectroscopy, revealing some significant chemical shift modifications of the cyanine polymethine chain depending on the counter anion. A mesylated derivative of the cyanine-containing probe allowed the successful direct F-18-radiolabelling with a radiochemical yield of 18%. The F-18-radiolabelled fluorescent probe, obtained via [F-18]F-C bond formation, allows subsequent vector introduction for in vivo targeting, opening a broad scope of applications in imaging modalities and therapy.