title: Preparation of a potential positron emission tomographic radioligand for the dopamine transporter.
abstract: NNC 12-0722 (1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-methyl piperazine) is a new selective inhibitor of the dopamine transporter. [11C]NNC 12-0722 was prepared by N-methylation of the desmethyl compound with [11C]methyl iodide. The total radiochemical yield of [11C]NNC 12-0722 was 40%-50% with an overall synthesis time of 30-35 min. The radiochemical purity was higher than 99% and the specific radioactivity about 1500 Ci/mmol (55 GBq/mumol). Autoradiographic examination of [11C]NNC 12-0722 binding on whole hemisphere cryosections from human brain post mortem demonstrated specific binding in the caudate nucleus and putamen. In a positron emission tomographic examination of [11C]NNC 12-0722 in a cynomolgus monkey there was a rapid uptake of radioactivity in the brain. In the striatum, a region with a high density of dopamine transporters, the radioactivity was two times higher than in the cerebellum. These results indicate that [11C]NNC 12-0722 may be a useful radioligand for labelling of the dopamine transporter in man.
authors.affiliation: Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: C
authors.initials: C
authors.lastname: Foged
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.forename: H
authors.initials: H
authors.lastname: Hall
authors.forename: C G
authors.initials: CG
authors.lastname: Swahn
authors.forename: P D
authors.initials: PD
authors.lastname: Suzdak
authors.forename: R
authors.initials: R
authors.lastname: Hohlweg
authors.forename: E B
authors.initials: EB
authors.lastname: Nielsen
authors.forename: L
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002352:Carrier Proteins / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis*; D051381:Rats; D014055:Tomography, Emission-Computed
chemical_list: D002352:Carrier Proteins; C086871:NNC 12-0722; D009419:Nerve Tissue Proteins; D010879:Piperazines; D004298:Dopamine