In:
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 32, No. 1 ( 2012-01), p. 127-136
Abstract:
[ 11 C]PHNO is a D 2 /D 3 agonist positron emission tomography radiotracer, with higher in vivo affinity for D 3 than for D 2 receptors. As [ 11 C]-( + )-PHNO is an agonist, its in vivo binding is expected to be more affected by acute fluctuations in synaptic dopamine than that of antagonist radiotracers such as [ 11 C]raclopride. In this study, the authors compared the effects of an oral dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of [ 11 C]-( + )-PHNO and [ 11 C]raclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D 3 receptors is negligible and both tracers predominantly bind to D2 receptors, the reduction of [ 11 C]-( + )-PHNO binding potential ( BP ND ) was 1.5 times larger than that of [ 11 C]raclopride. The gain in sensitivity associated with the agonist [ 11 C]-( + )-PHNO implies that ~65% of D 2 receptors are in the high-affinity state in vivo. In extrastriatal regions, where [ 11 C]-( + )-PHNO predominantly binds to D 3 receptors, the amphetamine effect on [ 11 C]-( + )-PHNO BP ND was even larger, consistent with the higher affinity of dopamine for D 3 . This study indicates that [ 11 C]- ( + )-PHNO is superior to [ 11 C]raclopride for studying acute fluctuations in synaptic dopamine in the human striatum. [ 11 C]-( + )-PHNO also enables measurement of synaptic dopamine in D 3 regions.
Type of Medium:
Online Resource
ISSN:
0271-678X
,
1559-7016
DOI:
10.1038/jcbfm.2011.115
Language:
English
Publisher:
SAGE Publications
Publication Date:
2012
detail.hit.zdb_id:
2039456-1
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