title: In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB.
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.
authors.affiliation: 1 Department of Psychiatry, Stony Brook University, Stony Brook, USA.|2 Department of Biomedical Engineering, Stony Brook University, Stony Brook, USA.|3 Department of Psychiatry, Columbia University, New York, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: DeLorenzo
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: 1 Department of Psychiatry, Stony Brook University, Stony Brook, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gardus
authors.affiliation: 5 Department of Preventive Medicine, Stony Brook University, Stony Brook, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: 3 Department of Psychiatry, Columbia University, New York, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Labaree
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.
authors.forename: Yiyun H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: 3 Department of Psychiatry, Columbia University, New York, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: 6 Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.affiliation: 3 Department of Psychiatry, Columbia University, New York, USA.|7 Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: 3 Department of Psychiatry, Columbia University, New York, USA.|7 Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, USA.|8 Department of Pharmacology, Columbia University, New York, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Javitch
authors.affiliation: 1 Department of Psychiatry, Stony Brook University, Stony Brook, USA.|2 Department of Biomedical Engineering, Stony Brook University, Stony Brook, USA.|9 Department of Radiology, Stony Brook University, Stony Brook, USA.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.|10 Department of Biomedical Engineering, Yale University, New Haven, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: 4 Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA.|11 Department of Psychiatry, Yale University, New Haven, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D057054:Molecular Imaging; D009570:Nitriles / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; C527000:3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile; C578935:GRM5 protein, human; D009570:Nitriles; D010091:Oximes; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5
keywords: Positron emission tomography; [11C]ABP688; [18F]FPEB; metabotropic glutamate receptor subtype 5; test–retest