Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography: I. Accuracy and Precision of D2 Receptor Parameter Measurements in Ventral Striatum

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Abstract
Dopamine transmission in the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and in the reinforcing effects of virtually all drugs of abuse. The aim of this study was to assess the accuracy and precision of measurements of D2 receptor availability in the VST obtained with positron emission tomography on the high-resolution ECAT EXACT HR+ scanner (Siemens Medical Systems, Knoxville, TN, U.S.A.). A method was developed for identification of the boundaries of the VST on coregistered high-resolution magnetic resonance imaging scans. Specific-to-nonspecific partition coefficient (V3″) and binding potential (BP) of [11C]raclopride were measured twice in 10 subjects, using the bolus plus constant infusion method. [11C]Raclopride V3″ in the VST (1.86 ± 0.29) was significantly lower than in the dorsal caudate (DCA, 2.33 ± 0.28) and dorsal putamen (DPU, 2.99 ± 0.26), an observation consistent with postmortem studies. The reproducibility of V3″ and BP were appropriate and similar in VST (V3″ test–retest variability of 8.2% ± 6.2%, intraclass correlation 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 analysis revealed that activities in the VST were significantly contaminated by counts spilling over from the adjacent DCA and DPU: 70% ± 5% of the specific binding measured in the VST originated from D2 receptors located in the VST, whereas 12% ± 3% and 18% ± 3% were contributed by D2 receptors in the DCA and DPU, respectively. Thus, accuracy of D2 receptor measurement is improved by correction for partial voluming effects. The demonstration of an appropriate accuracy and precision of D2 receptor measurement with [11C]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.