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

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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 (BP(ND) s) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BP(ND) estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BP(ND) levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BP(ND) s. BP(ND) 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.

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          Author and article information

          Journal
          Synapse
          Synapse (New York, N.Y.)
          Wiley
          1098-2396
          0887-4476
          Sep 2012
          : 66
          : 9
          Affiliations
          [1 ] Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110, USA.
          Article
          NIHMS382844
          10.1002/syn.21566
          3389593
          22535514
          263f7d11-1839-44b0-bfe7-2d5446db5d98
          Copyright © 2012 Wiley Periodicals, Inc.
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