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

Michael Kassiou, Ursula Scheffel, Hayden T Ravert, William B. Mathews, John L. Musachio, Richard M. Lambrecht, Robert F. Dannals

Research output: Contribution to journalArticlepeer-review

Abstract

[11C]A-69024, (±)-1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-[1 1C]methyl-1,2,3,4-tetra-hydroisoquinoline, 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-adminstration 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 (α1), and haloperidol (D2/σ) 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.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNuclear Medicine and Biology
Volume22
Issue number2
DOIs
StatePublished - Feb 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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