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Synthesis, labelling and first evaluation of [ 18 F]R91150 as a serotonin 5‐HT 2A receptor antagonist for PET
Author(s) -
Mühlhausen Ute,
Ermert Johannes,
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.1565
Subject(s) - chemistry , radiosynthesis , receptor , in vivo , radioligand , ex vivo , ligand (biochemistry) , serotonin , binding potential , 5 ht receptor , antagonist , radiochemistry , positron emission tomography , pharmacology , in vitro , biochemistry , neuroscience , psychology , medicine , microbiology and biotechnology , biology
In psychiatric disorders such as anxiety, depression and schizophrenia, 5‐HT 2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high‐affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high‐affinity ligand for 5‐HT 2A receptors, was labelled with fluorine‐18. This was accomplished in six steps via 4‐[ 18 F]fluorophenol and 1‐(3‐bromopropoxy)‐4‐[ 18 F]fluorobenzene within 190 min starting from no‐carrier‐added [ 18 F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/µmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [ 18 F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5‐HT 2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd.