title: [11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography.
abstract: The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occurred within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [11C]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [11C]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience] Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lundkvist
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: N
authors.initials: N
authors.lastname: Ginovart
authors.forename: S
authors.initials: S
authors.lastname: Nyberg
authors.forename: C G
authors.initials: CG
authors.lastname: Swahn
authors.forename: A A
authors.initials: AA
authors.lastname: Carr
authors.forename: F
authors.initials: F
authors.lastname: Brunner
authors.forename: L
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008252:Macaca fascicularis; D008745:Methylation; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D005464:Fluorobenzenes; D006847:Hydrocarbons, Iodinated; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C014055:methyl iodide; C079049:volinanserin