Reproducibility of Post-Amphetamine [11C]FLB 457 Binding to Cortical D2/3 Receptors

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. © 2013 Narendran et al.