Media type: E-Article Title: Synthesis, radiofluorination and first evaluation of (±)‐[18F]MDL 100907 as serotonin 5‐HT2A receptor antagonist for PET Contributor: Mühlhausen, Ute; Ermert, Johannes; Herth, Matthias M.; Coenen, Heinz H. imprint: Wiley, 2009 Published in: Journal of Labelled Compounds and Radiopharmaceuticals, 52 (2009) 1, Seite 6-12 Language: English DOI: 10.1002/jlcr.1563 ISSN: 0362-4803; 1099-1344 Keywords: Organic Chemistry ; Spectroscopy ; Drug Discovery ; Radiology, Nuclear Medicine and imaging ; Biochemistry ; Analytical Chemistry Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>In some psychiatric disorders 5‐HT<jats:sub>2A</jats:sub> receptors play an important role. In order to investigate those <jats:italic>in vivo</jats:italic> there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent <jats:italic>in vivo</jats:italic> properties of [<jats:sup>11</jats:sup>C]MDL 100907 for PET imaging of 5‐HT<jats:sub>2A</jats:sub> receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[<jats:sup>18</jats:sup>F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[<jats:sup>18</jats:sup>F]MDL 100907 was obtained with a specific activity of at least 30 GBq/µmol (EOS) and an overall radiochemical yield of 1–2%. In order to verify its binding to 5‐HT<jats:sub>2A</jats:sub> receptors, <jats:italic>in vitro</jats:italic> rat brain autoradiography was conducted showing the typical distribution of 5‐HT<jats:sub>2A</jats:sub> receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [<jats:sup>18</jats:sup>F]MDL 100907 appears to be a promising new 5‐HT<jats:sub>2A</jats:sub> PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.</jats:p>