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

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 D(2) 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 (V(3)") and binding potential (BP) of [(11)C]raclopride were measured twice in 10 subjects, using the bolus plus constant infusion method. [(11)C]Raclopride V(3)" 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 V(3)" and BP were appropriate and similar in VST (V(3)" 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 D(2) receptors located in the VST, whereas 12% +/- 3% and 18% +/- 3% were contributed by D(2) receptors in the DCA and DPU, respectively. Thus, accuracy of D(2) receptor measurement is improved by correction for partial voluming effects. The demonstration of an appropriate accuracy and precision of D(2) receptor measurement with [(11)C]raclopride in the VST is the first critical step toward the use of this ligand in the study of synaptic dopamine transmission at D(2) receptors in the VST using endogenous competition techniques.

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

“…To our knowledge, these results provide the first evidence that APTD decreases stimulated DA release in human brain. The effect of APTD on d-amphetamine-induced changes in striatal [ 11 C]raclopride BP was restricted to limbic and associative subcompartments, as defined by Laruelle, Haber, and co-workers (Haber and McFarland, 1999;Mawlawi et al, 2001;Martinez et al, 2003). This agrees with previous observations that d-amphetamine preferentially decreases [ 11 C]raclopride BP in these regions (Drevets et al, 2001; Leyton et al, 2002;Martinez et al, 2003).…”

“…Significant correlations were seen in the t-map Figure 1 Depicted is a schematic representation of ROI, as defined by Mawlawi et al (2001). On the left, the ROI are delineated by ANIMAL-INSECT segmentation (Collins and Evans, 1997) 8 mm rostral to the anterior commissure.…”

“…Second, the striatum was delineated from a probabilistic brain atlas (Collins et al, 1994a). Third, the study's ROI were drawn within the striatum's boundaries, based on the functional organization of limbic, associative, and sensory motor subcompartments as proposed by Laruelle, Haber, and co-workers (Haber and McFarland, 1999;Mawlawi et al, 2001;Martinez et al, 2003) ( Figure 1): ventral striatum (limbic striatum), precommissural dorsal caudate (posterior caudate/associative striatum), precommissural dorsal putamen (posterior putamen/associative striatum), postcommissural caudate (anterior caudate/associative striatum), and postcommissural putamen (anterior putamen/sensory motor putamen). The ROI were drawn on each subject's MRI to match their individual neuroanatomy, and the same regions were used for both the first and second scans.…”

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

“…The caudate nucleus and putamen were divided anatomically into precommissural and postcommissural sections. The VST was defined according to Mawlawi et al 18 The thalamus and cerebellum were drawn on transaxial slices. Neocortical ROIs were created using FreeSurfer software (version 5.3; http://surfer.nmr.mgh.harvard.edu/), which can be used to produce ROIs for PET data analysis with high anatomic accuracy.…”

“…15 The region of interest (ROI) measurement of striatal D 2/3 receptor binding using single-bolus [ 11 C]raclopride injection is highly reliable. [16][17][18] In most test-retest studies, scans have been performed on the same day [17][18][19] and only one study has documented long-term reproducibility. 16 Long-term stability is essential for follow-up studies using pharmacological or behavioral challenges, where the interval between measurements can be relatively long.…”