Synthesis, radiofluorination and first evaluation of (+/-)-[F-18]MDL 100907 as serotonin 5-HT2A receptor antagonist for PET

In some psychiatric disorders 5-HT2A 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 [C-11]MDL 100907 for PET imaging of 5-HT2A receptors and the more suitable half-life of fluorine-18, MDL 100907 was radiofluorinated in four steps using 1-(2-bromoethyl)-4-[F-18]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and [+/-)-[F-18]MDL 100907 was obtained with a specific activity of at least 30 GBq/mu mol (EOS) and an overall radiochemical yield of 1-2%. In order to verify its binding to 5-HT2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5-HT2A receptors and a very low non-specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [F-18]MDL 100907 appears to be a promising new 5-HT2A PET ligand.