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ID: ALA1152377

Journal: Bioorg Med Chem Lett

Title: [(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies.

Authors: Riss PJ, Hooker JM, Alexoff D, Kim SW, Fowler JS, Rösch F.

Abstract: PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [(11)C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [(11)C]MeI mediated synthesis of [(11)C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb(2)CO(3) in DMF in up to 95+/-5% labelling yield. A preliminary muPET-experiment demonstrates the reversible, highly specific binding of [(11)C]PR04.MZ in the brain of a male Sprague-Dawley rat.

CiteXplore: 19525112

DOI: 10.1016/j.bmcl.2009.05.090