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

• Published in: Journal of cerebral blood flow and metabolism 2017-08, Vol.37 (8), p.2716-2727
• Main Authors: DeLorenzo, Christine, Gallezot, Jean-Dominique, Gardus, John, Yang, Jie, Planeta, Beata, Nabulsi, Nabeel, Ogden, R Todd, Labaree, David C, Huang, Yiyun H, Mann, J John, Gasparini, Fabrizio, Lin, Xin, Javitch, Jonathan A, Parsey, Ramin V, Carson, Richard E, Esterlis, Irina
• Format: Article
• Language: English
• Subjects: Adult; Brain - diagnostic imaging; Brain - metabolism; Female; Healthy Volunteers; Humans; Image Processing, Computer-Assisted; Male; Molecular Imaging; Nitriles - pharmacology; Original; Oximes - pharmacology; Positron-Emission Tomography - methods; Protein Binding; Pyridines - pharmacology; Radiopharmaceuticals; Receptor, Metabotropic Glutamate 5 - metabolism; Reproducibility of Results; Sensitivity and Specificity
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X16673646

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 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.