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

Abstract

The design and synthesis of ¹⁸F-radiolabelled and fluorescent dual imaging agents allowing bimodal PET/FLI imaging is a current challenge. We report herein the development of a cyanine-based [¹⁸F]F-C-glycosyl dual imaging probe for fluorescence imaging (FLI) and a robust [¹⁸F]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 α_vβ₃ integrin targeting. As attested by the in vitro evaluation, the novel dual agent demonstrates affinity for α_vβ₃ integrins in the nanomolar range (IC₅₀ = 398 nM). This fluorescent dual agent was fully characterized by photophysical measurements (λ_abs/λ_em = 643/660 nm, Φ_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 ¹⁸F-radiolabelling with a radiochemical yield of 18%. The ¹⁸F-radiolabelled fluorescent probe, obtained via [¹⁸F]F–C bond formation, allows subsequent vector introduction for in vivo targeting, opening a broad scope of applications in imaging modalities and therapy.