title: A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey.
abstract: This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D(2)-like receptor agonist, (R)-2-(11)CH(3)O-N-n-propylnorapomorphine ([(11)C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D(2) receptor (D(2)R). MNPA is a selective D(2)-like receptor agonist with a high affinity (K(i)=0.17 nM). [(11)C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [(11)C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D(2)R, with a maximum striatum-to-cerebellum ratio of 2.23+/-0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37+/-0.06 at 72 min. The pretreatment study demonstrated high specific binding to D(2)R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [(11)C]MNPA has potential as an agonist radioligand for the D(2)-like receptor and has potential for examination of the high-affinity state of the D(2)R in human subjects and patients with neuropsychiatric disorders.
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska University Hospital, S-17176 Stockholm, Sweden.
authors.forename: Sjoerd J
authors.initials: SJ
authors.lastname: Finnema
authors.forename: Nicholas
authors.initials: N
authors.lastname: Seneca
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.forename: Evgeny
authors.initials: E
authors.lastname: Shchukin
authors.forename: Judit
authors.initials: J
authors.lastname: Sóvágó
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Håkan V
authors.initials: HV
authors.lastname: Wikström
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D008252:Macaca fascicularis; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C009074:N-n-propylnorapomorphine; D001058:Apomorphine