High long-term test–retest reliability for extrastriatal ¹¹C-raclopride binding in healthy older adults

Abstract

In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test–retest reliability in a sample of younger adults. The present work demonstrates high seven-month test–retest reliability of striatal and extrastriatal 11C-raclopride BPND values in healthy, older adults (n = 27, age: 64–78 years). Mean 11C-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85–0.96), absolute variability was low (mean: 4–8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional 11C-raclopride BPND values correlated with previously determined 18F-fallypride BPND values (ρ = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: ρ = 0.92; p < 0.001; excluding striatum: ρ = 0.75; p = 0.067). These observations suggest that extrastriatal 11C-raclopride measurements represent a true D2 signal.

Dopamine facilitates fear memory formation in the human amygdala

“…However, these studies have rarely included the amygdala or applied single scan bolus/infusion paradigms which arguably adds to the sensitivity of the measure. Moreover, test-retest reliability of amygdala [ 11 C]raclopride BP has been reported to be high (21). Also, here we found similar changes in [ 11 C]raclopride BP ND in the amygdala and the striatum, although amygdala release had higher variability, whereas our control region, the frontal cortex did not indicate dopamine release.…”

“…1). We used single scan bolus/infusion of [ 11 C]raclopride (20,21) to measure conditioning-related change in binding potential (i.e., dopamine release) (15), combined with functional magnetic resonance imaging (fMRI) to measure neural activity. We predicted that increased dopamine levels in the amygdala during fear conditioning would facilitate learning (8,13,14), with greater dopamine release related to superior cue discrimination and enhanced amygdala-located fear engram formation.…”

Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine

“…Finally, we repeated the k ‐means clustering but instead of the [ 11 C]raclopride‐PET template, we used estimates of D 2/3 R availability obtained from a [ 18 F]fallypride‐PET template (Castrellon et al, 2019). This was done to ensure that the segmentation results are not affected by differences in presentation of striatal and extra‐striatal D 2/3 R availability with these two radiotracers (Karalija et al, 2020; Svensson et al, 2019).…”

Relative Strengths of Three Linearizations of Receptor Availability: Saturation, Inhibition, and Occupancy Plots

“…where B is the quantity of bound ligand. The binding potential is defined as the ratio of the volumes of distribution of specifically bound ("displaceable") and non-specifically bound ("nondisplaceable") ligand quantities (14,15). To determine the binding potential of a radioligand, the volumes of distribution are entered into the relationship that defines the binding potential (2,5,16):…”