Within-Subject Comparison of [11C]-( + )-PHNO and [11C]raclopride Sensitivity to Acute Amphetamine Challenge in Healthy Humans

[11C]PHNO is a D2/D3 agonist positron emission tomography radiotracer, with higher in vivo affinity for D3 than for D2 receptors. As [11C]-( + )-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 suc...

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Published in:Journal of cerebral blood flow and metabolism Vol. 32; no. 1; pp. 127 - 136
Main Authors: Shotbolt, Paul, Tziortzi, Andri C, Searle, Graham E, Colasanti, Alessandro, van der Aart, Jasper, Abanades, Sergio, Plisson, Christophe, Miller, Sam R, Huiban, Mickael, Beaver, John D, Gunn, Roger N, Laruelle, Marc, Rabiner, Eugenii A
Format: Journal Article
Language:English
Published: London, England SAGE Publications 01.01.2012
Nature Publishing Group
Sage Publications Ltd
Subjects:
Adult
Amphetamine - blood
Amphetamine - pharmacology
Binding, Competitive
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Development. Senescence. Regeneration. Transplantation
Dopamine - metabolism
Dopamine Agonists - pharmacokinetics
Dopamine Antagonists - pharmacokinetics
Dopamine D2 Receptor Antagonists
Fundamental and applied biological sciences. Psychology
Humans
Ligands
Male
Medical sciences
Middle Aged
Neurology
Original
Oxazines - pharmacokinetics
Positron-Emission Tomography - methods
Protein Binding
Raclopride - pharmacokinetics
Radioligand Assay
Radiopharmaceuticals - pharmacokinetics
Receptors, Dopamine D2 - agonists
Receptors, Dopamine D3 - agonists
Receptors, Dopamine D3 - antagonists & inhibitors
Sensitivity and Specificity
Vascular diseases and vascular malformations of the nervous system
Vertebrates: nervous system and sense organs
brain imaging
neurochemistry
positron emission tomography
dopamine
receptor imaging
Amphetamine derivatives
Human
Nervous system diseases
Raclopride
Dopamine
CNS stimulant
Neuroleptic
Psychotropic
Dopamine antagonist
Catecholamine
Cerebral disorder
Encephalon
D2 Dopamine receptor
Central nervous system disease
Neurotransmitter
Amfetamine
Positron emission tomography
Comparative study
Cerebrovascular disease
Emission tomography
ISSN:0271-678X, 1559-7016
Online Access:Get full text
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Summary:[11C]PHNO is a D2/D3 agonist positron emission tomography radiotracer, with higher in vivo affinity for D3 than for D2 receptors. As [11C]-( + )-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 [11C]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 [11C]-( + )-PHNO and [11C]raclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D3 receptors is negligible and both tracers predominantly bind to D2 receptors, the reduction of [11C]-( + )-PHNO binding potential (BPND) was 1.5 times larger than that of [11C]raclopride. The gain in sensitivity associated with the agonist [11C]-( + )-PHNO implies that ~65% of D2 receptors are in the high-affinity state in vivo. In extrastriatal regions, where [11C]-( + )-PHNO predominantly binds to D3 receptors, the amphetamine effect on [11C]-( + )-PHNO BPND was even larger, consistent with the higher affinity of dopamine for D3. This study indicates that [11C]- ( + )-PHNO is superior to [11C]raclopride for studying acute fluctuations in synaptic dopamine in the human striatum. [11C]-( + )-PHNO also enables measurement of synaptic dopamine in D3 regions.
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ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.2011.115