Measuring dopamine transporter occupancy by cocaine in vivo: radiotracer considerations

Synapse
J S FowlerG J Wang

Abstract

Several recent neuroimaging studies in humans and in monkeys using different radiotracers have reported widely differing values of dopamine transporter (DAT) occupancy by doses of cocaine which are perceived as reinforcing by humans. Here we tested the hypothesis that the measurement of DAT occupancies by drugs with fast pharmacokinetics such as cocaine requires a radioligand with similar kinetics in order to effectively compete with the drug. We measured DAT occupancy by four different doses of cocaine (1.0, 0.5, 0.25, and 0.1 mg/kg) using [11C]d-threo-methylphenidate (a radiotracer which binds rapidly to the DAT in vivo) and compared them to estimates reported previously using [11C]cocaine in the same two baboons and with the same four doses of cocaine [Volkow et al. (1996b) Synapse 24:399-402). Cocaine reduced [11C]d-threo-methylphenidate binding in striatum in a dose-dependent manner, and values were significantly correlated with those obtained previously with [11C]cocaine (r = 0.9, F = 37, P < 0.001). The ED50s (50% occupancy of DAT by cocaine) were 0.27 and 0.17 mg/kg for [11C]d-threo-methylphenidate and [11C]cocaine, respectively. This is significantly lower than values obtained with labeled beta-CIT and other similar ra...Continue Reading

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Citations

Dec 22, 1999·Pharmacology & Therapeutics·G EmilienS Cragg
Oct 1, 2003·Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T·Joanna S. FowlerStephen L. Dewey
Oct 17, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Erik B OlesonEvgeny A Budygin
Jun 16, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sunmee WeeWilliam L Woolverton
Jul 21, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·George V Rebec
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Dec 1, 2006·Neuropsychiatric Disease and Treatment·Feng LiuRaul R Silva
Jul 1, 2014·Addiction Biology·Eun Young JangHee Young Kim
Apr 20, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bradley T ChristianJogeshwar Mukherjee
Nov 26, 2008·Nuclear Medicine and Biology·Shil Patel, Raymond Gibson
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Jan 15, 2020·Temperature : Multidisciplinary Biomedical Journal·Eugene A Kiyatkin
Jul 25, 2018·ACS Chemical Neuroscience·Ernesto SolisEugene A Kiyatkin

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