title: [11C]A-69024: a potent and selective non-benzazepine radiotracer for in vivo studies of dopamine D1 receptors.
abstract: [11C]A-69024, (+/-)-1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-[11C]methyl- 1,2,3,4-tetrahydroisoquinoline, is a specific and selective dopamine D1 radiotracer. The in vivo biodistribution of this novel radioligand in mice showed a high uptake in the striatum (6.7% ID/g) at 5 min, followed by clearance with a half-life of 16.1 min. As a measure of specificity, the striatal/cerebellar ratio reached a maximum of 7.4 at 30 min post-injection. Radioactivity in the striatum was reduced to the level of the cerebellum by pre-administration of the D1 antagonist SCH 23390 (1 mg/kg). Pretreatment of mice with spiperone (D2), 7-hydroxydipropylaminotetralin (7-OH-DPAT) (D3), clozapine (D4), ketanserin (5-HT2/5-HT2C), mazindol (monoamine reuptake), prazosin (alpha 1), and haloperidol (D2/sigma) had no inhibitory effect on [11C]A-69024 uptake in the striatum. The dextrorotatory enantiomer of the dopamine antagonist butaclamol inhibited striatal uptake, while the less active isomer (-)-butaclamol did not. [11C]A-69024 binding was inhibited by unlabeled A-69024 in a dose dependent manner (ED50 = 0.3 mg/kg) in the striatum while no change occurred in the cerebellum. [11C]A-69024 warrants further investigation as a PET ligand for examination of central dopamine D1 receptors in humans.
authors.affiliation: Biomedicine and Health Program, Australia Nuclear Science and Technology Organisation, N.S.W., Sydney.
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: W B
authors.initials: WB
authors.lastname: Mathews
authors.forename: J L
authors.initials: JL
authors.lastname: Musachio
authors.forename: R M
authors.initials: RM
authors.lastname: Lambrecht
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009830:Olfactory Bulb / Q000378:metabolism; D010208:Papaverine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044005:Tetrahydroisoquinolines; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; C061450:A 69024; D010208:Papaverine