A Comparative Evaluation of the Dopamine D-2/3 Agonist Radiotracer [C-11](-)-N-Propyl-norapomorphine and Antagonist [C-11]Raclopride to Measure Amphetamine-Induced Dopamine Release in the Human Striatum

作者：Narendran Rajesh^*; Mason N Scott; Laymon Charles M; Lopresti Brian J; Velasquez Natalie D; May Maureen A; Kendro Steve; Martinez Diana; Mathis Chester A; Frankle W Gordon

来源：Journal of Pharmacology and Experimental Therapeutics, 2010, 333(2): 533-539.

DOI：10.1124/jpet.109.163501

(-)-N-Propyl-norapomorphine (NPA) is a full dopamine D-2/3 receptor agonist, and [C-11] NPA is a suitable radiotracer to image D-2/3 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 [C-11]NPA to acute fluctuation in synaptic dopamine was assessed with PET in healthy humans and compared with that of the reference D-2/3 receptor antagonist radiotracer [C-11]raclopride. Ten subjects (eight females and two males) were studied on two separate days, a minimum of 1 week apart, both with [C-11] raclopride and [C-11] 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). [C-11]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. [C-11]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 [C-11] NPA is more vulnerable to endogenous competition by dopamine compared with [C-11]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 D-2/3 agonist radiotracers are more vulnerable to endogenous competition by dopamine than existing D-2/3 antagonist radiotracers.

• 出版日期2010-5