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

Sarah A. Eisenstein, Jon M. Koller, Marilyn Piccirillo, Ana Kim, Jo Ann V. Antenor-Dorsey, Tom O. Videen, Abraham Z. Snyder, Morvarid Karimi, Stephen M. Moerlein, Kevin J. Black, Joel S. Perlmutter, Tamara Hershey

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)770-780
Number of pages11
JournalSynapse
Volume66
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Binding potential
  • D2 receptor
  • Dopamine
  • Extrastriatal
  • Radioligand

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