Synthesis, radiofluorination and first evaluation of (±)‐[ 18 F]MDL 100907 as serotonin 5‐HT 2A receptor antagonist for PET

In some psychiatric disorders 5‐HT 2A receptors play an important role. In order to investigate those in vivo 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 in vivo properties of [ 11 C]MDL 100907 for PET imaging of 5‐HT 2A receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[ 18 F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[ 18 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 2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5‐HT 2A receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [ 18 F]MDL 100907 appears to be a promising new 5‐HT 2A PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.