[11C]A-69024: a potent and selective non-benzazepine radiotracer for in vivo studies of dopamine D1 receptors

Nucl Med Biol. 1995 Feb;22(2):221-6. doi: 10.1016/0969-8051(94)00086-y.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Binding, Competitive
  • Biological Transport
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Cerebellum / metabolism
  • Cerebral Cortex / metabolism
  • Corpus Striatum / metabolism
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Olfactory Bulb / metabolism
  • Papaverine / analogs & derivatives*
  • Papaverine / metabolism
  • Papaverine / pharmacokinetics
  • Radioligand Assay
  • Receptors, Dopamine D1 / analysis
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism*
  • Tetrahydroisoquinolines
  • Tissue Distribution

Substances

  • Carbon Radioisotopes
  • Receptors, Dopamine D1
  • Tetrahydroisoquinolines
  • A 69024
  • Papaverine