[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 journalArticle

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

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ASJC Scopus subject areas

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

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