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.

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

Figure 1.

V_T from test (x axis) and retest (y axis) scans using [¹¹C]ABP688 (left) and [¹⁸F]FPEB (right). The solid red line is the line of identity. All scans were performed on the same day except [¹¹C]ABP688 Subject 1.

Figure 2.

Average percent difference (between test and retest scans) in V_T (V_TPD = 100 × [V_T^retest—V_T^test]/V_T^test) for [¹¹C]ABP688 (left) and [¹⁸F]FPEB (right). V_TPD was measured and averaged over nine regions: anterior cingulate, medial prefrontal cortex, orbitofrontal cortex, ventral striatum, parietal lobe, putamen, caudate, amygdala and hippocampus. Standard deviation of the percent differences across these regions is represented by error bars. Subjects are presented in chronological order for each cohort. Blue bars represent male subjects and red bars represent female subjects. All subjects participated in test and retest scans on the same-day except for Subject 1 of the [¹¹C]ABP688 cohort, whose scans were two days apart.

Figure 3.

Average percent difference (between test and retest scans) in BP_ND′ (BP_ND′PD = 100 × [BP_ND′^retest—BP_ND′^test]/BP_ND′^test) for [¹¹C]ABP688 and [¹⁸F]FPEB. CU1-8 are [¹¹C]ABP688 subjects from a previous cohort, scanned at Columbia University. YU1-11 are the [¹¹C]ABP688 cohort examined in this paper. FPEB1-4 were scanned with [¹⁸F]FPEB. Both YU ABP688 and FPEB cohorts were scanned using the HRRT at the Yale PET Center. BP_ND′PD was measured and averaged over nine regions: anterior cingulate, medial prefrontal cortex, orbitofrontal cortex, ventral striatum, parietal lobe, putamen, caudate, amygdala and hippocampus. Standard deviation of the percent differences across these regions is represented by error bars. Blue bars represent male subjects and red bars represent female subjects.