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2 Publications

18F-radiolabeled S100 proteins as potential probes for molecular imaging of inflammatory processes in vivo

Hoppmann, S.; Richter, S.; Pietzsch, J.
Interaction of certain extracellular S100 proteins with the receptor for advanced glycation endproducts (RAGE) is considered to play a crucial role in various inflammatory diseases. However, data concerning the interaction of circulating S100 proteins with RAGE in inflammatory processes in vivo are scarce. One reason is the shortage of suitable radiotracer methods. To address this question, we report a novel methodology using recombinant human S100A1, S100B, and S100A12 for radiolabeling with the positron emitter fluorine-18 (18F) and the use of 18F-S100 proteins in cell association assays in vitro and in dynamic small animal positron emission tomography (PET) studies in Wistar rats in vivo. Human S100 proteins were cloned in the bacterial expression vector pGEX-6P-1, expressed in E. coli BL21, and purified. Purified S100 proteins were radiolabeled with N-succinimidyl-4-[18F]fluorobenzoate. Cellular association studies in human THP-1 macrophages and human aortic endothelial cells (HAEC) showed specific binding of all 18F-S100 proteins to the non-internalizing RAGE as confirmed by inhibitory effects exerted either by other RAGE ligands, e.g., glycated LDL, or by soluble RAGE. Of interest, uptake of 18F-S100 proteins in THP-1 and HAEC mediated by various scavenger receptors was observed. The in vitro data are consistent with in vivo PET data showing a pronounced temporary association of 18F-S100 proteins with tissues expressing RAGE, e.g., lung and vessels. Moreover, a significant accumulation of 18F-S100 proteins in tissues that are rich in cells expressing scavenger receptors (tissue macrophages) such as liver and spleen was observed. In conclusion, 18F-labeling of S100 proteins and the use of small animal PET provide a valuable tool to discriminate the kinetics and the metabolic fate of S100 proteins in vivo. Furthermore, the approach provides novel probes for imaging of RAGE-ligand interaction in inflammatory processes, e.g., in rodent models of disease.
  • Poster
    5th International EDHF Symposium - Endothelium, Vasoactive Factors and Inflammation, 24.-27.06.2008, Tampere, Finland
  • Abstract in refereed journal
    Basic & Clinical Pharmacology & Toxicology 102(2008)S1, 49

Permalink: https://www.hzdr.de/publications/Publ-11354
Publ.-Id: 11354