Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET.
The radiotracer [(11)C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [(11)C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [(11)C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [(11)C]PHNO and [(11)C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [(11)C]PHNO or [(11)C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7 ± 8%), the nucleus accumbens (10 ± 7%), and in the globus pallidus (13 ± 15%) measured with [(11)C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [(11)C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [(11)C]PHNO compared with [(11)C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [(11)C]PHNO is more sensitive than [(11)C]raclopride to nicotine- and amphetamine-induced DA release. [(11)C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers.
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
Jean-Dominique
JD
Gallezot
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Tracy
T
Kloczynski
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
David
D
Weinzimmer
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
David
D
Labaree
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
Ming-Qiang
MQ
Zheng
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
Keunpoong
K
Lim
GlaxoSmithKline, London, UK.
Eugenii A
0000000336126687
EA
Rabiner
GlaxoSmithKline, London, UK.
Khanum
K
Ridler
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Brian
B
Pittman
Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
Yiyun
Y
Huang
1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA.
Richard E
RE
Carson
1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA.
Evan D
ED
Morris
1] Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Kelly P
KP
Cosgrove
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010078:Oxazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride / Q000493:pharmacokinetics
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D010078:Oxazines; C042631:naxagolide; D020891:Raclopride; D009538:Nicotine; D000661:Amphetamine; D004298:Dopamine