Imaging and functional characterization of the receptor for advanced glycation endproducts (RAGE) in vivo

RAGE has been implicated in the pathogenesis of various disorders including inflammatory processes and cancerogenesis. However, data concerning the functional expression of RAGE in inflammatory lesions and other pathologies in vivo are scarce. We report a novel radiotracer approach using radiolabeling of various RAGE ligands, including S100 proteins (S100B/S100A12), glycated low-density lipoproteins (glycLDL), and glycated albumin (glycBSA) with the positron emitter fluorine-18
(18F) and the application of 18F-labeled RAGE ligands in dynamic small animal positron emission tomography (PET) studies. Radiolabeling of proteins was performed by conjugation with no-carrier added N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) causing no adverse alterations of the biological functionality of the proteins in vitro.
Biodistribution and metabolite studies in rodent normal, inflammatory, and tumor models revealed high in vivo-stability for the 18F-RAGE ligands. The in vivo-kinetics of 18F-RAGE ligands, with or without presence of specific ligands/inhibitors of RAGE and various scavenger receptors, in rodent models was quantified by PET, and correlated well with the anatomical localization of RAGE, e.g., in blood vessels, lungs, inflammatory lesions, and tumors. 18F-radiolabeling of S100 proteins, glycLDL and glycBSA and the use of small animal PET provide potential probes to measure functional expression of RAGE under normal and pathophysiological conditions in vivo.