RT Journal Article
SR Electronic
T1 A Comparative Evaluation of the Dopamine D<sub>2/3</sub> Agonist Radiotracer [<sup>11</sup>C](−)-<em>N</em>-Propyl-norapomorphine and Antagonist [<sup>11</sup>C]Raclopride to Measure Amphetamine-Induced Dopamine Release in the Human Striatum
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 533
OP 539
DO 10.1124/jpet.109.163501
VO 333
IS 2
A1 Rajesh Narendran
A1 N. Scott Mason
A1 Charles M. Laymon
A1 Brian J. Lopresti
A1 Natalie D. Velasquez
A1 Maureen A. May
A1 Steve Kendro
A1 Diana Martinez
A1 Chester A. Mathis
A1 W. Gordon Frankle
YR 2010
UL http://jpet.aspetjournals.org/content/333/2/533.abstract
AB (−)-N-Propyl-norapomorphine (NPA) is a full dopamine D2/3 receptor agonist, and [11C]NPA is a suitable radiotracer to image D2/3 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study, the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic dopamine was assessed with PET in healthy humans and compared with that of the reference D2/3 receptor antagonist radiotracer [11C]raclopride. Ten subjects (eight females and two males) were studied on two separate days, a minimum of 1 week apart, both with [11C]raclopride and [11C]NPA at baseline and after the administration of 0.5 mg · kg−1 oral d-amphetamine. Kinetic modeling with an arterial input function was used to derive the binding potential relative to nonspecific uptake (BPND) in the ventral striatum (VST), caudate (CAD), and putamen (PUT). [11C]Raclopride BPND was significantly reduced by 9.7 ± 4.4, 8.4 ± 4.2, and 14.7 ± 4.8% after amphetamine administration in the VST, CAD, and PUT. [11C]NPA BPND was also reduced significantly, by 16.0 ± 7.0, 16.1 ± 6.1, and 21.9 ± 4.9% after the same dose of amphetamine in the VST, CAD, and PUT. Although these results suggest that [11C]NPA is more vulnerable to endogenous competition by dopamine compared with [11C]raclopride by a factor of 1.49 to 1.90, the same data for a related outcome measure, binding potential relative to plasma concentration, was not significant. Nevertheless, these data add to the growing literature that suggests D2/3 agonist radiotracers are more vulnerable to endogenous competition by dopamine than existing D2/3 antagonist radiotracers. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics