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

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 [(11)C]FLB 457. Herein we report on reproducibility and reliability of [(11)C]FLB 457 binding potential relative to non-displaceable uptake (BP(ND)) following an acute amphetamine challenge. Ten healthy human subjects were studied twice with [(11)C]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 (V(T)), binding potential relative to plasma concentration (BP(P)), and BP(ND) of [(11)C]FLB 457. The test-retest variability of [(11)C]FLB 457 V(T), BP(P) and BP(ND) 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 [(11)C]FLB 457 BP(ND) is reproducible. These data further support the use [(11)C]FLB 457 and amphetamine to characterize cortical dopamine transmission in neuropsychiatric disorders.