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ID: ALA1139978

Journal: Bioorg Med Chem Lett

Title: Synthesis and radiopharmacological characterization of [11C]AL-438 as a nonsteroidal ligand for imaging brain glucocorticoid receptors.

Authors: Wuest F, Kniess T, Bergmann R, Henry B, Pietzsch J.

Abstract: The radiosynthesis and the radiopharmacological characterization of [(11)C]AL-438 as a nonsteroidal ligand for the glucocorticoid receptor (GR) is described. Radiolabeling of the corresponding desmethyl precursor 10 with [(11)C]MeI gave [(11)C]AL-438 in decay-corrected radiochemical yields of 30+/-4% (based upon [(11)C]CO(2)) within 35 min at a specific radioactivity of 10-15 GBq/micromol at the end-of-synthesis. The radiopharmacological evaluation of [(11)C]AL-438 involved biodistribution and small animal PET imaging in rats, and autoradiography studies using rat brain sections. Biodistribution studies were performed in male Wistar rats and demonstrated high radioactivity uptake in pituitary and brain. However, the inability of high dose corticosterone to block binding would suggest that the radioactivity accumulation in the brain was not receptor-mediated.

CiteXplore: 17499506

DOI: 10.1016/j.bmcl.2007.04.094