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...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Journal of cerebral blood flow and metabolism Ročník 32; číslo 1; s. 127 - 136
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London, England SAGE Publications 01.01.2012 Nature Publishing Group Sage Publications Ltd
Témata:	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
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	[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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 content type line 23
ISSN:	0271-678X 1559-7016
DOI:	10.1038/jcbfm.2011.115