Positron Emission Tomography Imaging of Dopamine D2/3 Receptors in the Human Cortex With [11C]FLB 457: Reproducibility Studies

In a recent PET study, we demonstrated the ability to measure amphetamine- induced DA release in the human cortex with the relatively high affinity dopamine D-2/3 radioligand [C-11]FLB 457 (Narendran et al., [2009] Synapse 63: 447-461). The aim of this study was to evaluate the reproducibility and reliability of [C-11]FLB 457 in the same imaging paradigm we used to measure amphetamine-induced DA transmission. Six healthy human subjects (three males/three females) were studied twice with [C-11]FLB 457, once at baseline and again 3 h following the end of the baseline scan. D-2/3 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 (BPP), and binding potential relative to nondisplaceable uptake (BPND) of [(11) C] FLB 457. The test-retest variability of [C-11]FLB 457 V-T, BPP, and BPND were <= 15%, consistent with the published test-retest variability for this ligand in other brain regions (Sudo et al., [2001] Nucl Med Commun 22: 1215-1221; Vilkman et al., [2000] Eur J Nucl Med 27: 1666-1673). In addition, no significant decrease in [C-11] FLB 457 BPND was observed in the second scan compared to the first one. This suggests that the contribution of carryover mass of [C-11]FLB 457 to the measured reduction in [C-11] FLB 457 BPND following amphetamine was relatively low. These data support the further validation of [C-11]FLB 457 as a tool to measure amphetamine-induced dopamine release in the human cortex. Synapse 65:35-40, 2011. (C) 2010 Wiley-Liss, Inc.