Test-retest reproducibility of extrastriatal dopamine D-2 receptor imagingwith [I-123]epidepride SPECT in humans

This study evaluated the test-retest reproducibility of D-2 receptor quanti fication in the thalamus and temporal cortex using [I-123]epidepride SPECT. Methods: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) under went 2 SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusio n paradigm (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma cle arance (in liters per hour) and free fraction (f(1)) of the parent tracer w ere measured. Radioactivity (in becquerels per gram) in the thalamus, tempo ral cortex, and cerebellum were normalized to the infusion rate (in becquer els per hour). Normalized striatal radioactivity was also measured to asses s reproducibility in regions with a high density of receptors and better co unting statistics. The outcome measures obtained were V-3 (receptor density [B-max]/equilibrium dissociation constant [K-D]), V-3' (f(1) X B-max/K-D), and R-T (Specific-to-nondisplaceable tissue ratio). Results: Test-retest v ariability and reliability (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for plasma clearance and 15.3% and 0.77, respective ly, for f(1). The test-retest variability of brain-specific (target minus n ondisplaceable) radioactivity was higher in the thalamus and temporal corte x than in the striatum, although reliability was comparable. Among the outc ome measures, V-3' showed better test-retest variability and reliability in the thalamus (13.3% and 0.75, respectively) and temporal cortex (13.4% and 0.86, respectively). Conclusion: Brain radioactivity was the main source o f variability for quantification of extrastriatal D-2 receptors with [I-123 ]epidepride. The reproducibility of outcome measures in extrastriatal regio ns was good. However, because receptor density was lower in extrastriatal r egions than in the striatum, the counting statistics in these regions were low and reproducibility was affected by the higher test-retest variability of brain-specific radioactivity. Compared with V-3 and V-3', R-T showed les s test-retest variability in the thalamus and temporal cortex but lower rel iability. Moreover, measurement of R-T may be affected by the presence of p otential lipophilic metabolites entering the brain.