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 (D2/3R) 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 D2/3R antagonist. (ii) To assess test-retest repeatability, nine subjects were examined twice. Non displaceable binding potential (BPND) was quantified using the simplified reference tissue model with cerebellum as reference. Quetiapine dosing was associated with decrease in [11C]raclopride BPND 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 D2/3R in extrastriatal regions. •Extrastriatal [11C]raclopride binding characteristics has not been well described.•D2-blocking agent gave little to no decrease in extrastriatal [11C]raclopride binding.•Test-retest repeatability was generally poor in cortical regions.•[11C]raclopride PET is not an apt tool for extrastriatal D2/3R binding quantification.