C-glycosyl compounds: multifunctional scaffolds for the development of dual imaging tools
Abstract
Close analogs of O-glycosides, C-glycosyl compounds display chemical and biological stabilities toward enzymatic hydrolysis and are thus used to build bioactive compounds, peptidomimetics and more complex sugars. In this work, C-glycosyl compounds are selected as multifunctional scaffolds for the development of imaging tools. More precisely, we focused here on bimodal molecular imaging, a current trend which combined two complementary modalities: PET (Positron Emission Tomography) and NIRF (Near Infra-Red Fluorescence). Two C-glycosyl scaffolds are thus functionalized in a regiocontrolled manner in order to introduce the key elements at different stages: a fluorescent cyanine derivative for NIRF, a fluorine-18 atom for PET and two c(RGDfK) peptides targeting integrins overexpressed in some malignant tumours. The copper-catalyzed alkyne-azide cycloaddition (CuAAC) was used for the introduction of the fluorophore and for the bioconjugation step with peptides. In vitro and in vivo evaluations by fluorescence imaging and the resection of the tumor demonstrated the potential of the conjugates in glioblastoma cancer diagnosis and image-guided surgery.