Abstract
In a recent positron emission tomography (PET) study, we demonstrated the ability to measure amphetamine-induced dopamine (DA) release in the human cortex with the relatively high affinity dopamine D2/3 radioligand [11C]FLB 457. Herein we report on reproducibility and reliability of [11C]FLB 457 binding potential relative to non-displaceable uptake (BPND) following an acute amphetamine challenge. Ten healthy human subjects were studied twice with [11C]FLB 457 following an acute amphetamine (oral, 0.5 mg kg-1 dose) challenge on two-separate days approximately one week apart. D2/3 receptor binding parameters were estimated using a two-tissue compartment kinetic analysis in the cortical regions of interest and cerebellum (reference region). The test-retest variability and intraclass correlation coefficient were assessed for distribution volume (VT), binding potential relative to plasma concentration (BPP), and BPND of [11C]FLB 457. The test-retest variability of [11C]FLB 457 VT, BPP and BPND were ≤ 17%, 22% and 11% respectively. These results, which are consistent with the published test-retest variability for this ligand measured under baseline conditions demonstrate that the post-amphetamine [11C]FLB 457 BPND is reproducible. These data further support the use [11C]FLB 457 and amphetamine to characterize cortical dopamine transmission in neuropsychiatric disorders.
Highlights
The competition between dopamine (DA) and D2/3 radiotracer binding following an amphetamine challenge is a noninvasive measure of the change in extracellular DA induced by the challenge [1,2,3,4,5,6,7] and is thought to provide information as to the status of DA transmission in the brain
We demonstrated that the test-retest variability for [11C]FLB 457 binding potential relative to nondisplaceable uptake (BPND) measured under control conditions is an acceptable ≤ 15% in the cortical regions of interest -- a result which is consistent with other published [11C]FLB 457 reproducibility studies [14,18,19]
Values are the mean of 10 subjects with each value measured twice
Summary
The competition between dopamine (DA) and D2/3 radiotracer binding (such as [11C]raclopride and [123I]IBZM) following an amphetamine challenge is a noninvasive measure of the change in extracellular DA induced by the challenge [1,2,3,4,5,6,7] and is thought to provide information as to the status of DA transmission in the brain. The results of this study, which showed a significant reduction in the in vivo binding of [11C]FLB 457 following oral amphetamine (0.5 mg kg-1) led to further characterization of this imaging paradigm as a tool to measure cortical DA release. We demonstrated that the test-retest variability for [11C]FLB 457 BPND measured under control conditions (i.e., at baseline) is an acceptable ≤ 15% in the cortical regions of interest -- a result which is consistent with other published [11C]FLB 457 reproducibility studies [14,18,19]. We were interested in evaluating the test-retest variability of the post-amphetamine [11C]FLB 457 BPND to ensure that it is reproducible.
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