In vivo positron emission tomography imaging with [11C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons

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.

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in vivo Variation in Metabotropic Glutamate Receptor Subtype 5 Binding Using Positron Emission Tomography and [11C]ABP688

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.105 ◽

2011 ◽

Vol 31 (11) ◽

pp. 2169-2180 ◽

Cited By ~ 50

Author(s):

Christine DeLorenzo ◽

J S Dileep Kumar ◽

J John Mann ◽

Ramin V Parsey

Keyword(s):

Positron Emission Tomography ◽

Glutamate Receptor ◽

Metabotropic Glutamate Receptor ◽

Preliminary Evidence ◽

Emission Tomography ◽

Receptor Subtype ◽

Metabotropic Glutamate ◽

Pet Tracer ◽

Positron Emission

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders. Recently, a positron emission tomography (PET) tracer exhibiting high selectivity and specificity for mGluR5, 3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime ([11C]ABP688), was developed. In this work, eight healthy adult male humans were imaged twice to assess within-subject [11C]ABP688 binding variability using PET. In seven of the eight subjects, significantly higher binding was observed during the second (retest) scan. This binding increase could not be definitively explained by differences in ligand injected mass or dose, or changes in metabolism between scans. In addition, this type of systematic binding increase was not observed in a [11C]ABP688 test–retest study performed by our group on anaesthetized baboons. It is therefore possible that the increased binding was because of physiological changes occurring between scans, such as changes in endogenous glutamate levels. If PET imaging with [11C]ABP688 could detect such differences, as preliminary evidence suggests, it could be used to help uncover the role of glutamate in the pathophysiology of brain disorders. However, regardless of its ability to detect endogenous glutamate differences, [11C]ABP688 binding variability could make accurate assessments of drug occupancy or group differences using this ligand difficult.

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