Parametric in vivo imaging of benzodiazepine receptor distribution in human brain

Authors

  • Dr. Kirk A. Frey MD, PhD,

    Corresponding author
    1. Division of Nuclear Medicine (Department of Internal Medicine), University of Michigan, Ann Arbor, MI
    2. Mental Health Research Institute, University of Michigan, Ann Arbor, MI
    • Division of Nuclear Medicine, B1 G412 University Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0028
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  • Vjera A. Holthoff MD,

    1. Max-Planck-Institut für Neurologische Forschung, Köln, Federal Republic of Germany
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  • Robert A. Koeppe PhD,

    1. Division of Nuclear Medicine (Department of Internal Medicine), University of Michigan, Ann Arbor, MI
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  • Douglas M. Jewett PhD,

    1. Division of Nuclear Medicine (Department of Internal Medicine), University of Michigan, Ann Arbor, MI
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  • Michael R. Kilbourn PhD,

    1. Division of Nuclear Medicine (Department of Internal Medicine), University of Michigan, Ann Arbor, MI
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  • David E. Kuhl MD

    1. Division of Nuclear Medicine (Department of Internal Medicine), University of Michigan, Ann Arbor, MI
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Abstract

Emission computed tomographic methods for the in vivo quantification of radioligand-binding sites in human brain have previously been limited either by a lack of correction for possible effects of altered ligand transport or by highly complicated physiological models that preclude display of binding data in a detailed anatomical format. We investigated the application of a simplified compartmental model to the kinetic analysis of in vivo ligand binding to central benzodiazepine receptors. The human brain distribution of {11C}flumazenil, as determined by dynamic positron emission tomography, combined with metabolite-corrected arterial blood samples, permitted estimations of local cerebral ligand transport and of receptor binding. This approach allows calculation of transport and binding “maps” on a pixel-by-pixel basis, resulting in the display of binding data in a familiar tomographic format while maintaining much of the physiological accuracy inherent in more complex methods. The results obtained in a study of 6 normal volunteers revealed good interindividual precision, with coefficients of variation between 10 and 15% of mean regional values, suggesting the utility of this approach in future clinical studies of benzodiazepine receptor binding.

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