Error analysis for PET measurement of dopamine D2 receptor occupancy by antipsychotics with [11C]raclopride and [11C]FLB 457 (cas 107188-66-9)

Add time:08/13/2019    Source:sciencedirect.com

Dopamine D2 receptor occupancy by antipsychotic drugs has been measured with positron emission tomography (PET) by comparing the binding potential (BP) values before and after drug administration. This occupancy has been found to be related to clinical effects and side effects. In this study, we evaluated the uncertainty of the quantitative analysis for estimating the dopamine D2 receptor occupancy by antipsychotics in simulation and human studies of [11C]raclopride and for the high affinity ligand [11C]FLB 457. Time–activity curves of [11C]raclopride and [11C]FLB 457 were simulated, and the reliability of BP estimated by a simplified reference tissue model and the calculated occupancy were investigated for various noise levels, BP values, and scan durations. Then, in the human PET study with and without antipsychotics, the uncertainty of BP and occupancy estimates and the scan duration required for a reliable estimation were investigated by a bootstrap approach. Reliable and unbiased estimates of [11C]raclopride BPND could be obtained with recording as short as 32 min, with the relative standard deviation (SD) of the striatal occupancy remaining less than 10%. Conversely, in [11C]FLB 457 studies, the mean value increased and SD of the temporal cortex and thalamus exceeded 10% when the scan duration was shorter than 60 min. These results demonstrated that dopamine D2 receptor occupancy by antipsychotics can be estimated precisely with an optimal scan duration with [11C]raclopride and [11C]FLB 457.

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