title: Synthesis and cerebral uptake of 1-(1-[(11)C]methyl-1H-pyrrol-2-yl)-2-phenyl-2-(1-pyrrolidinyl)ethanone, a novel tracer for positron emission tomography studies of monoamine oxidase type A.
abstract: ( R)-(-)- and ( S)-(+)-1-(1-[ (11)C]methyl-1 H-pyrrol-2-yl)-2-phenyl-2-(1-pyrrolidinyl)ethanone 4 and 5 were synthesized, and their properties as tracers for positron emission tomography (PET) studies of monoamine oxidase type A (MAO-A) in the brain of living pigs were tested. Parametric maps of the distribution volume ( V d) 4 in pig brain were qualitatively similar to those obtained with [ (11)C]harmine, with prominent binding in the ventral forebrain and mesencephalon. Its binding was highly vulnerable to MAO blockade, suggesting a binding potential as high as 2 for MAO-A sites. The slow plasma metabolism of 4 and 5 may present advantages over [ (11)C]harmine for routine PET studies of MAO-A.
authors.affiliation: PET Centre, Aarhus University Hospital, Nørrebrogade 44, Arhus C, Denmark. svend@pet.auh.dk
authors.forename: Svend Borup
authors.initials: SB
authors.lastname: Jensen
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.forename: Aage Kristian
authors.initials: AK
authors.lastname: Olsen
authors.forename: Kasper
authors.initials: K
authors.lastname: Pedersen
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013552:Swine; D014018:Tissue Distribution
chemical_list: C529392:1-(1-methyl-1H-pyrrol-2-yl)-2-phenyl-2-(1-pyrrolidinyl)ethanone; D011758:Pyrroles; D011759:Pyrrolidines; D008995:Monoamine Oxidase