Molecular imaging of the receptor for advanced glycation endproducts

The receptor for advanced glycation endproducts (RAGE) is a member of the immunoglobulin superfamily and has been implicated in the pathogenesis of various disorders including inflammatory processes and cancerogenesis. However, data concerning the functional expression of RAGE in inflammatory compartments and other pathologies in vivo are scarce. We report a multi-radiotracer approach using radiolabeling of various RAGE ligands, including glycated low-density lipoproteins (glycLDL), glycated albumin (glycBSA), and S100 proteins (S100B and S100A12) 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 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 stability for the 18F-RAGE ligands in vivo. The in vivo kinetics of 18F-RAGE ligands, with or without presence of specific ligands or inhibitors of RAGE and, additionally, various scavenger receptors, in rodent models was quantified by PET, and correlated well with the anatomical localization of RAGE, e.g., in lung, endothelium, inflammatory lesions, and tumors.
18F-radiolabeling of glycLDL, glycBSA, and S100 proteins and the use of small animal PET provide a potential approach to measure the functional expression of RAGE under normal and pathophysiological conditions in vivo.
Supported by Deutsche Forschungsgemeinschaft (Pi 304/1-1)