Journal
SYNAPSE
Volume 63, Issue 6, Pages 447-461Publisher
WILEY
DOI: 10.1002/syn.20628
Keywords
PET; dopamine; [C-11]FLB 457; [C-11]fallypride; amphetamine and human cortex
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The use of PET and SPELT endogenous competition binding techniques has contributed to the understanding of the role of dopamine in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of acute changes in synaptic dopamine have been restricted to the striatum. The ligands previously used, such as [C-11]racloprideand [I-123]IBZM, do not provide sufficient signal to noise ratio to quantify D-2 receptors in extrastriatal areas, such as cortex, where the concentration of D-2 receptors is much lower than in the striatum. Given the importance of cortical DA function in cognition, a method to measure cortical dopamine function in humans would be highly desirable. The goal of this study was to compare the ability of two high affinity DA D-2 radioligands [C-11]FLB 457 and [C-11]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. D-2 receptor availability was measured in the cortical regions of interest with PET in 12 healthy volunteers under control,and postamphetamine conditions (0.5 mg kg(-1), oral), using both [C-11]FLB 457 and [C-11]fallypride (four scans per subjects). Kinetic modeling with an arterial input function was used to derive the binding potential (BPND) in eight cortical regions. Under controlled conditions, [C-11]FLB 457 BPND was 30-70% higher compared with [C-11]fallypride BPND in cortical regions. Amphetamine induced DA release led to a significant decrease in [C-11]FLB 457 BPND in five out the eight cortical regions evaluated. In contrast, no significant decrease in [C-11]fallypride BPND was detected in cortex following amphetamine. The difference between [C-11]FLB 457 and [C-11]fallypride ability to detect changes in the cortical D-2 receptor availability following amphetamine is: related to the higher signal to noise ratio provided by [C-11]FLB 457. These findings suggest that [C-11]FLB 457 is superior to [C-11]fallypride for measurement of changes in cortical synaptic dopamine. Synapse 63:447-461, (C) 2009. 2009 Wiley-Liss, Inc.
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