In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB

J Cereb Blood Flow Metab. 2017 Aug;37(8):2716-2727. doi: 10.1177/0271678X16673646. Epub 2016 Jan 1.

Abstract

Positron emission tomography tracers [11C]ABP688 and [18F]FPEB target the metabotropic glutamate receptor subtype 5 providing quantification of the brain glutamatergic system in vivo. Previous [11C]ABP688 positron emission tomography human test-retest studies indicate that, when performed on the same day, significant binding increases are observed; however, little deviation is reported when scans are >7 days apart. Due to the small cohorts examined previously (eight and five males, respectively), we aimed to replicate the same-day test-retest studies in a larger cohort including both males and females. Results confirmed large within-subject binding differences (ranging from -23% to 108%), suggesting that measurements are greatly affected by study design. We further investigated whether this phenomenon was specific to [11C]ABP688. Using [18F]FPEB and methodology that accounts for residual radioactivity from the test scan, four subjects were scanned twice on the same day. In these subjects, binding estimates increased between 5% and 39% between scans. Consistent with [11C]ABP688, mean absolute test-retest variability was previously reported as <12% when scans were >21 days apart. This replication study and pilot extension to [18F]FPEB suggest that observed within-day binding variation may be due to characteristics of mGluR5; for example, diurnal variation in mGluR5 may affect measurement of this receptor.

Keywords: Positron emission tomography; [11C]ABP688; [18F]FPEB; metabotropic glutamate receptor subtype 5; test–retest.

MeSH terms

  • Adult
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Female
  • Healthy Volunteers
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Molecular Imaging
  • Nitriles* / pharmacology
  • Oximes* / pharmacology
  • Positron-Emission Tomography / methods*
  • Protein Binding
  • Pyridines* / pharmacology
  • Radiopharmaceuticals
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
  • 3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile
  • GRM5 protein, human
  • Nitriles
  • Oximes
  • Pyridines
  • Radiopharmaceuticals
  • Receptor, Metabotropic Glutamate 5