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Characterization of extrastriatal D2 in vivo specific binding of [18F](N-methyl)benperidol using PET

Authors

  • Sarah A. Eisenstein,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Jon M. Koller,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Marilyn Piccirillo,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Ana Kim,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Jo Ann V. Antenor-Dorsey,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Tom O. Videen,

    1. Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    2. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
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  • Abraham Z. Snyder,

    1. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
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  • Morvarid Karimi,

    1. Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Stephen M. Moerlein,

    1. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
    2. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Kevin J. Black,

    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    2. Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    3. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
    4. Department of Anatomy and Neurobiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
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  • Joel S. Perlmutter,

    1. Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    2. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
    3. Department of Anatomy and Neurobiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    4. Program in Physical Therapy, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63108
    5. Program in Occupational Therapy, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63108
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  • Tamara Hershey

    Corresponding author
    1. Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    2. Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110
    3. Division of Radiological Sciences, Washington University School of Medicine in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110
    • Campus Box 8225, 4525 Scott Avenue, Washington University School of Medicine, St. Louis, MO 63110, USA
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Abstract

PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [18F]N-methylbenperidol ([18F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [18F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR-PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [18F]NMB injection. Regional peak radioactivity was identified using a peak-finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individual's MR image and tissue activity curves were extracted from coregistered PET images. [18F]NMB binding potentials (BPNDs) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BPND estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BPND levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BPNDs. BPND estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [18F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states. Synapse 66:770–780, 2012. © 2012 Wiley Periodicals, Inc.

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