What were they thinking? Cognitive states may influence [11C]raclopride binding potential in the striatum

Abstract

[(11)C]Raclopride ([(11)C]RAC) is a selective dopamine D(2)/D(3) antagonist that is commonly used in positron emission tomography (PET) studies to assess both basal levels of receptor availability and changes in availability caused by alterations in striatal dopamine concentration. When designing [(11)C]RAC studies, it is important to understand what variables may affect the results. Here, we examined differences in baseline striatal [(11)C]RAC binding potential (BP(ND)) under two different "rest" conditions. Thirteen subjects received [(11)C]RAC scans. Eight subjects were aware prior to initiation of scanning that they would receive a "baseline" scan, and that no additional procedures would take place during the scan ("certain rest" group, CER). Five subjects were informed that they might or might not receive an i.v. alcohol infusion during the scan ("uncertain rest" group, UNC). This group was informed five min after scan start that they would not receive alcohol. Voxel-wise analyses of binding potential (BP(ND)) images generated for both "rest" conditions indicated that receptor availability was higher in UNC than in CER. This result was confirmed by a region-of-interest analysis, which indicated that the average BP(ND) in right and left putamen was statistically higher in UNC. There were no differences in groups with respect to age or raclopride mass dose that could account for the difference in D(2)/D(3) receptor availability. Our findings suggest that even slight differences in cognitive states between groups can have an effect on BP(ND), presumably mediated by changes in endogenous dopamine concentration.

FIGURE 1

SPM results for contrast between striatal binding potential images; UNC > CER. CER, certain. UNC, uncertain. Statistical threshold: p < 0.005, uncorrected. Display threshold: p < 0.01. Colorbar indicates t-values for each contrast. Crosshairs indicate peak t-values within each cluster. Left: Peak voxel is in the left anterior putamen, at MNI coordinate (-20, 16, -8). Right: Peak voxel is in the right posterior putamen, at MNI coordinate (32, 2, -2).

FIGURE 2

Mean [¹¹C]raclopride binding potential from the ROI analysis. CER, certain. UNC, uncertain. A. Mean ± SD for left and right caudate. B. Mean ± SD for left and right putamen. *Statistically different from CER, p < 0.03.