title: [18F]fluoroalkyl analogues of the potent 5-HT1A antagonist WAY 100635: radiosyntheses and in vivo evaluation.
abstract: Two analogues of the potent 5-HT1A antagonist WAY 100635 have been synthesized and radiolabelled with 18F, namely N-[2-[4-(2-2'-[18F] fluoroethoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide ([18F]FEC) and N-[2-[4-(2-3'-[18F] fluoropropoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exa ne carboxamide ([18F]FPC). Biodistribution studies in rats showed selective uptake of both radiotracers in regions known to be rich in 5-HT1A receptors following i.v. injection. The ratio of radioactivity in hippocampus to that in the cerebellum was 5.5 (for [18F]FEC) and 7.5 (for [18F]FPC) at 60 min postinjection. Regional brain heterogeneity of radioactivity could be abolished by pretreatment with WAY 100635 and FPC but was unaffected by pretreatment with a variety of drugs including ketanserin, sulpiride, and SCH 23390. These results are compared vis-a-vis with those obtained using [11C]WAY 100635 to evaluate [18F]FEC and [18F]FPC as potential radiotracers for imaging 5-HT1A receptors by positron emission tomography.
authors.affiliation: PET Centre, Clarke Institute of Psychiatry, University of Toronto Faculty of Medicine, On, Canada.
authors.forename: A A
authors.initials: AA
authors.lastname: Wilson
authors.forename: J N
authors.initials: JN
authors.lastname: DaSilva
authors.forename: S
authors.initials: S
authors.lastname: Houle
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011854:Radiochemistry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; C102682:N-(2-(4-(2-(2'-fluoroethoxy)phenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide; C102683:N-(2-(4-(2-(3'-fluoropropoxy)phenyl)-1-piperazinyl)ethyl)-N-(2-pyridnyl)cyclohexane carboxamide; D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists