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Synthesis, radiofluorination and first evaluation of (±)‐[ 18 F]MDL 100907 as serotonin 5‐HT 2A receptor antagonist for PET
Author(s) -
Mühlhausen Ute,
Ermert Johannes,
Herth Matthias M.,
Coenen Heinz H.
Publication year - 2009
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1563
Subject(s) - radioligand , chemistry , spiperone , ketanserin , receptor , in vivo , 5 ht receptor , serotonin , radioligand assay , ligand (biochemistry) , positron emission tomography , antagonist , stereochemistry , neuroscience , biochemistry , psychology , biology , microbiology and biotechnology
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.