title: Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline +-[11C]A-69024 and positron emission tomography.
abstract: In vivo pharmacokinetic and brain binding characteristics of (+)-[(11)C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and beta-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[(11)C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[(11)C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive (+/-)A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[(11)C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography.
authors.affiliation: CNRS, URA 2210, 4 place du Général Leclerc, F-91406 Orsay, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Besret
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hérard
authors.forename: Martine
authors.initials: M
authors.lastname: Guillermier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Demphel
authors.forename: Françoise
authors.initials: F
authors.lastname: Hinnen
authors.forename: Christine
authors.initials: C
authors.lastname: Coulon
authors.forename: Michèle
authors.initials: M
authors.lastname: Ottaviani
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D013045:Species Specificity; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics