Positron emission tomography imaging of dopamine D2/3 receptors in the human cortex with [11C]FLB 457: Reproducibility studies

Abstract

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 [¹¹C]FLB 457 (Narendran et al., [2009] Synapse 63:447–461). The aim of this study was to evaluate the reproducibility and reliability of [¹¹C]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 [¹¹C]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 (BP_P), and binding potential relative to nondisplaceable uptake (BP_ND) of [¹¹C]FLB 457. The test–retest variability of [¹¹C]FLB 457 V_T, BP_P, and BP_ND 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 [¹¹C]FLB 457 BP_ND was observed in the second scan compared to the first one. This suggests that the contribution of carryover mass of [¹¹C]FLB 457 to the measured reduction in [¹¹C]FLB 457 BP_ND following amphetamine was relatively low. These data support the further validation of [¹¹C]FLB 457 as a tool to measure amphetamine‐induced dopamine release in the human cortex. Synapse 65:35–40, 2011.