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

• 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
• DOI: 10.1038/jcbfm.2011.115

[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.