Back to Search
Start Over
Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans.
- Source :
-
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2012 Jan; Vol. 32 (1), pp. 127-36. Date of Electronic Publication: 2011 Aug 31. - Publication Year :
- 2012
-
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 D(2) 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.
- Subjects :
- Adult
Amphetamine blood
Binding, Competitive
Brain drug effects
Brain metabolism
Dopamine metabolism
Dopamine D2 Receptor Antagonists
Humans
Ligands
Male
Middle Aged
Protein Binding
Radioligand Assay
Radiopharmaceuticals pharmacokinetics
Receptors, Dopamine D2 agonists
Receptors, Dopamine D3 agonists
Receptors, Dopamine D3 antagonists & inhibitors
Sensitivity and Specificity
Amphetamine pharmacology
Dopamine Agonists pharmacokinetics
Dopamine Antagonists pharmacokinetics
Oxazines pharmacokinetics
Positron-Emission Tomography methods
Raclopride pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-7016
- Volume :
- 32
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 21878947
- Full Text :
- https://doi.org/10.1038/jcbfm.2011.115