Validity and reliability of extrastriatal [¹¹C]raclopride binding quantification in the living human brain

[¹¹C]raclopride is a well established PET tracer for the quantification of dopamine 2/3 receptors (D_2/3R) in the striatum. Outside of the striatum the receptor density is up to two orders of magnitude lower. In contrast to striatal binding, the characteristics of extrastriatal [¹¹C]raclopride binding quantification has not been thoroughly described. Still, binding data for e.g., neocortex is frequently reported in the scientific literature. Here we evaluate the validity and reliability of extrastriatal [¹¹C]raclopride binding quantification. Two sets of healthy control subjects were examined with HRRT and [¹¹C]raclopride: (i) To assess the validity of extrastriatal [¹¹C]raclopride binding estimates, eleven subjects were examined at baseline and after dosing with quetiapine, a D_2/3R antagonist. (ii) To assess test-retest repeatability, nine subjects were examined twice. Non displaceable binding potential (BP_ND) was quantified using the simplified reference tissue model with cerebellum as reference. Quetiapine dosing was associated with decrease in [¹¹C]raclopride BP_ND in temporal cortex (18 ± 17% occupancy) and thalamus (20 ± 17%), but not in frontal cortex. Extrastriatal occupancy was lower than in putamen (51 ± 4%). The mean absolute variation was 4-7% in the striatal regions, 17% in thalamus, and 13-59% in cortical regions. Our data indicate that [¹¹C]raclopride PET, quantified using cerebellum as reference, is not a suitable tool to measure D_2/3R in extrastriatal regions.