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

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.

Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers

“…Despite these tracer dissimilarities, the current results of receptor availability decline with age show no differences in the net measurement of age effects when compared to previously studied ligands. This suggests a D 2 R specific mechanism in the dorsal striatum, similar to previous findings with [ 18 F]NMB and [ 11 C](+)PHNO (Eisenstein et al, 2012; Nakajima et al, 2015). …”

“…To date, studies have largely employed antagonist radiotracers (e.g., raclopride) that cannot differentiate D 2 vs. D 3 subtypes in either striatal or extrastriatal areas, with the exception of a preliminary study with [ 18 F] N -methylbenperidol ([ 18 F]NMB), a tracer with higher specificity for D 2 R. This work found decreases in striatal but not extrastriatal areas, although the latter regions had low BP ND that made accurate comparisons difficult (Eisenstein et al, 2012). Nonetheless, this study was the first to suggest age-related differences might be more specific in regards to D 2 R.…”

Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease

“…edu/fswiki/). Each participant's PET data were motion-corrected and registered to his or her MRI (82,83). Differences owing to image resolution across scanners were minimized by smoothing PET images to a common resolution of 8 mm isotropic (84).…”

Partial volume correction in quantitative amyloid imaging

“…Reconstructed PET images were smoothed to achieve a common spatial resolution of 8mm to minimize scanner differences (Joshi et al, 2009). Inter-frame motion correction for the dynamic PET images was performed using standard image registration techniques (Hajnal et al., 1995) implemented with in-house software (Eisenstein et al, 2012). PET-MR registration was performed using a vector-gradient algorithm (VGM) (Rowland et al, 2005) in a symmetric fashion (i.e.…”