Failure to detect amphetamine-induced dopamine release in the cortex with [¹¹ C]FLB 457 positron emission tomography...

Studies in nonhuman primates and humans have demonstrated that amphetamine-induced dopamine release in the cortex can be measured with [¹¹ C]FLB 457 and PET imaging. This technique has been successfully used in recent clinical studies to show decreased dopamine transmission in the prefrontal cortex in schizophrenia and alcohol dependence. Here, we present data from a cohort of twelve healthy controls in whom an oral amphetamine challenge (0.5 mg kg^-1 ) did not lead to a significant reduction in [¹¹ C]FLB 457 BP_ND (i.e., binding potential relative to non-displaceable uptake). Two factors that likely contributed to the inability to displace [¹¹ C]FLB 457 BP_ND in this cohort relative to successful cohorts are: (a) the acquisition of the baseline and post-amphetamine scans on different days as opposed to the same day and (b) the initiation of the post-amphetamine [¹¹ C]FLB 457 scan at ∼5 hours as opposed to ∼3 hours following oral amphetamine. Furthermore, we show [¹¹ C]FLB 457 reproducibility data from a legacy dataset to support greater variability in cortical BP_ND when the test and retest scans are acquired on different days as compared to the same day. These results highlight the methodological challenges that continue to plague the field with respect to imaging dopamine release in the cortex.