Synthesis, radiofluorination and first evaluation of (?)-(~(18)F)MDL 100907 as serotonin 5-HT_(2A) receptor antagonist for PET

摘要

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 140min and ( + )-[~(18)F]MDL 100907 was obtained with a specific activity of at least 30 GBq/mumol (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.