Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D-2 receptor parameter measurements inventral striatum

Dopamine transmission in the ventral striatum (VST), a structure which incl udes the nucleus accumbens. ventral caudate, and ventral putamen, plays a c ritical role in the pathophysiology of psychotic states and in the reinforc ing effects of virtually all drugs of abuse. The aim of this study was to a ssess the accuracy and precision of measurements of D-2 receptor availabili ty in the VST obtained with positron emission tomography on the high-resolu tion ECAT EXACT HR+ scanner (Siemens Medical Systems, Knoxville, TN, U.S.A. ). A method was developed for identification of the boundaries of the VST o n coregistered high-resolution magnetic resonance imaging scans. Specific-t o-nonspecific partition coefficient (V-3") and binding potential (BP) of [C -11]raclopride were measured twice in 10 subjects, using the bolus plus con stant infusion method. [C-11]Raclopride V-3" in the VST (1.86 +/- 0.29) was significantly lower than in the dorsal caudate (DCA, 2.33 +/- 0.28) and do rsal putamen (DPU, 2.99 +/- 0.26), an observation consistent with postmorte m studies. The reproducibility of V-3" and BP were appropriate and similar in VST (V-3" test-retest variability of 8.2% +/- 6.2%. intraclass correlati on coefficient = 0.83). DCA (7.7% +/- 5.1%, 0.77). DPU (6.0% +/- 4.1%, 0.71 ), and striatum as a whole (6.3% +/- 4.1%, 0.78). Partial volume effects an alysis revealed that activities in the VST were significantly contaminated by counts spilling over from the adjacent DCA and DPU: 70% +/- 5% of the sp ecific binding measured in the VST originated from D-2 receptors located in the VST, whereas 12% +/- 3% and 18% +/- 3% were contributed by D-2 recepto rs in the DCA and DPU, respectively. Thus, accuracy of D-2 receptor measure ment is improved by correction for partial voluming effects. The demonstrat ion of an appropriate accuracy and precision of D2 receptor measurement wit h [C-11]raclopride in the VST is the first critical step toward the use of this ligand in the study of synaptic dopamine transmission at D2 receptors in the VST using endogenous competition techniques.