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

J Cereb Blood Flow Metab. 2020 Sep;40(9):1859-1868. doi: 10.1177/0271678X19874770. Epub 2019 Sep 10.

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.

Keywords: 11C-raclopride; binding potential; extrastriatal; positron emission tomography; reliability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzamides
  • Carbon Radioisotopes
  • Cerebral Cortex / diagnostic imaging
  • Corpus Striatum / diagnostic imaging*
  • Dopamine Agonists / pharmacokinetics*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Pyrrolidines
  • Raclopride / pharmacokinetics*
  • Radiopharmaceuticals
  • Receptors, Dopamine D2 / metabolism*
  • Reproducibility of Results
  • Young Adult

Substances

  • Benzamides
  • Carbon Radioisotopes
  • Dopamine Agonists
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Raclopride