Test-retest variability of [¹¹C]raclopride-binding potential in nontreatment-seeking alcoholics

Abstract

Knowledge of the reproducibility of striatal [¹¹C]raclopride (RAC) binding is important for studies that use RAC PET paradigms to estimate changes in striatal dopamine (DA) during pharmacological and cognitive challenges. To our knowledge, no baseline test-retest data exist for nontreatment-seeking alcoholics (NTS). We determined the test-retest reproducibility of baseline RAC binding potential (BP(ND) ) in 12 male NTS subjects. Subjects were scanned twice with single-bolus RAC PET on separate days. Striatal RAC BP (BP(ND) ) for left and right dorsal caudate, dorsal putamen, and ventral striatum was estimated using the Multilinear Reference Tissue Method (MRTM) and Logan Graphical Analysis (LGA) with a reference region. Test-retest variability (TRV), % change in BP(ND) between scan days, and the intraclass correlation coefficient (ICC) were used as metrics of reproducibility. For MRTM, TRV for striatal RAC binding in NTS subjects was ±6.5% and ±7.1% for LGA. Average striatal ICCs were 0.94 for both methods (P < 0.0001). Striatal BP(ND) values were similar to those reported previously for detoxified alcoholics. The results demonstrate that baseline striatal RAC binding is highly reproducible in NTS subjects, with a low variance similar to that reported for healthy control subjects.

Figure 1

General outline of study protocol. Typically, the magnetic resonance image (MRI) was acquired on Day 1. BrAC: breath alcohol concentration. RAC: [¹¹C]raclopride positron emission tomography scan. Ratings were taken upon arrival, and before and after the resting (baseline) RAC scan.

Figure 2

Mean ± s.d. cigarette craving ratings from Day 1 (filled circles) and Day 2 (open triangles). The x-axis crosses the y-axis at the value of 4 to denote that 4 is the lowest possible score on the index; for reference, 20 is the highest possible score. Craving ratings did not vary within subjects across either day or time point (see text for details).

Figure 3

Mean ± s.d. alcohol craving score from the Alcohol Urge Questionnaire (AUQ) from Day 1 (filled circles) and Day 2 (open triangles). The x-axis crosses the y-axis at the value of 7 to denote that 7 is the lowest possible score on the index; for reference, 56 is the highest possible score. Craving ratings did not vary within subjects across either day or time point (see text for details).

Figure 4

Mean + s.d. CIWA-Ar ratings (for graphical clarity, only positive s.d. is shown) from Day 1 (filled squares) and Day 2 (open diamonds). CIWA-Ar score did not vary within subjects across either day or time point (see text for details). In this protocol, a score of ≥8 would require a subject to be withdrawn from the study to receive immediate medical attention for alcohol withdrawal symptoms.

Figure 5

BP_ND values from MRTM and LGA are highly correlated. The regression line (solid) almost overlaps with the line of identity (dashed). Pearson’s correlation coefficient and the significance value are denoted within the graph.

Figure 6

Test-retest variability (TRV) from MRTM plotted against TRV from LGA. The regression line (solid) deviates from the line of identity (dashed), but Pearson’s correlation coefficient is still highly statistically significant (inset).

Figure 7

Results from SPM analysis illustrating voxels in the right VST where BP_ND was lower on Day 2 relative to Day 1. Display threshold: p < 0.025. See text for details. The average % ΔBP_ND of the voxels in this cluster was −11.7 ± 10.3%. These results are consistent with the data in Table 2.