@article {Narendran533, author = {Rajesh Narendran and N. Scott Mason and Charles M. Laymon and Brian J. Lopresti and Natalie D. Velasquez and Maureen A. May and Steve Kendro and Diana Martinez and Chester A. Mathis and W. Gordon Frankle}, title = {A Comparative Evaluation of the Dopamine D2/3 Agonist Radiotracer [11C](-)-N-Propyl-norapomorphine and Antagonist [11C]Raclopride to Measure Amphetamine-Induced Dopamine Release in the Human Striatum}, volume = {333}, number = {2}, pages = {533--539}, year = {2010}, doi = {10.1124/jpet.109.163501}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {(-)-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 {\textperiodcentered} 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 {\textpm} 4.4, 8.4 {\textpm} 4.2, and 14.7 {\textpm} 4.8\% after amphetamine administration in the VST, CAD, and PUT. [11C]NPA BPND was also reduced significantly, by 16.0 {\textpm} 7.0, 16.1 {\textpm} 6.1, and 21.9 {\textpm} 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 {\textcopyright} 2010 by The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/333/2/533}, eprint = {https://jpet.aspetjournals.org/content/333/2/533.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }