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

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 (BP_ND) 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 BP_ND values in healthy, older adults (n = 27, age: 64-78 years). Mean ¹¹C-raclopride BP_ND 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 BP_ND values correlated with previously determined ¹⁸F-fallypride BP_ND 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.