Striatal and extrastriatal dopamine release measured with PET and [(18)F] fallypride

Abstract

The amphetamine challenge, in which positron emission tomography (PET) or single photon emission computed tomography radioligand binding following administration of amphetamine is compared to baseline values, has been successfully used in a number of brain imaging studies as an indicator of dopaminergic function, particularly in the striatum. [(18)F] fallypride is the first PET radioligand that allows measurement of the effects of amphetamine on D2/D3 ligand binding in striatum and extra-striatal brain regions in a single scanning session following amphetamine. We scanned 15 healthy volunteer subjects with [(18)F] fallypride at baseline and following amphetamine (0.3 mg/kg) using arterial plasma input-based modeling as well as reference region methods. We found that amphetamine effect was robustly detected in ventral striatum, globus pallidus, and posterior putamen, and with slightly higher variability in other striatal subregions. However, the observed effect sizes in striatum were less than those observed in previous studies in our laboratory using [(11)C] raclopride. Robust effect was also detected in limbic extra-striatal regions (hippocampus, amygdala) and substantia nigra, but the signal-to-noise ratio was too low to allow accurate measurement in cortical regions. We conclude that [(18)F] fallypride is a suitable ligand for measuring amphetamine effect in striatum and limbic regions, but it is not suitable for measuring the effect in cortical regions and may not provide the most powerful way to measure the effect in striatum.

Figure 1

Globus Pallidus ROI as drawn on one subject’s MRI. Lines in the sagittal slice (left) show slice levels of coronal (center) and transverse (right) slices.

Figure 2

BP_ND maps from SRTM pre and post amphetamine. A At the level of the striatum showing MRI (left), baseline (center) and post-amphetamin (right) in coronal (top) and tranverse (bottom) views. B. Extrastriatal, showing MRI (left) with line at the level of the tranverse slices at baseline (center) and post-amphetamine (right), at the level of the amygdala and temporal cortex (top) and midbrain nuclei (substantia nigra and superior colliculi, bottom). Note the truncated color scale in B, such that all BP_ND exceeding 2, including the striatum pre and post amphetamine, appear in red.

Figure 3

T maps of amphetamine effect from voxelwise analysis. Following SPM Gaussian random field based correction for multiple comparisons, statistically significant clusters were detected in putamen and ventral striatum only. The display threshold is set at p < 0.001.

Figure 4

Comparison [¹¹C] raclopride results to (Martinez et al., 2003). Mean [¹⁸F] fallypride regional decreases following amphetamine were of nearly identical magnitude (left) but the between subject variability was higher with the [¹⁸F] fallypride paradigm. This is reflected in the effect sizes (mean/SD) of the decrease following amphetamine (right). Region designations are as in Martinez et al. LST (Limbic striatum) is equivalent to the VST. AST (Associative striatum) is a composite of Pre-DCA, Pre-DPU and Post-CA. STR is a composite of all 5 striatal subregions.

Figure 5

Effect sizes in extrastriatal regions, displayed on the same scale as the striatal subregions.