Fluorine-18-radiolabeled S100A12: a potential probe for functional characterization of inflammatory processes in vivo
| Autor: | Hoppmann, S., Richter, S., Steinbach, J., Pietzsch, J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Zdroj: | 9th World Congress on Inflammation, 06.-10.07.2009, Tokyo, Japan Inflammation Research 58(2009)Suppl. 2, S145-S146 |
| Popis: | S100A12 has been implicated in inflammation. However, the role of extracellular S100A12 in vivo is still unclear. We report a novel methodology using radiolabeling of human recombinant S100A12 with the positron-emitter fluorine-18 and the use of 18F-S100A12 in cell assays in vitro and in small animal positron emission tomography (PET) studies in rats in vivo. For S100A12 radiolabeling N-succinimidyl-4-(18F)fluorobenzoate was used. S100A12 was shown to stimulate secretion of cytokines by macrophages and endothelial cells. In vitro assays revealed specific binding of 18F-S100A12 to the soluble receptor for advanced glycation endproducts (sRAGE) and, furthermore, to membrane RAGE on both cell types. Cell interaction of 18F-S100A12 was inhibited by RAGE inhibitors like glycated LDL and, interestingly, also by scavenger receptor ligands, e.g., maleylated albumin, and by lectines. PET data showed sustained temporary association of 18F-S100A12 with tissues expressing RAGE, e.g., lung and endothelium in vivo. Moreover, specific accumulation of 18F-S100A12 in tissues enriched in cells expressing scavenger receptors, e.g., liver and spleen, was observed. Concluding, 18F-radiolabeling of S100A12 and the use of PET allow discrimination of the kinetics and the metabolic fate of S100A12 in vivo. The approach provides a novel probe for functional characterization of inflammation in rodent models of disease. |
| Databáze: | OpenAIRE |
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