Abstract
(-)-N-Propyl-norapomorphine 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. 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 to that of the reference D2/3 receptor antagonist radiotracer [11C]raclopride. Ten subjects (8 Females/2 Males) were studied on two separate days, a minimum of one week apart, both with [11C]raclopride and [11C]NPA at baseline and following 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, BPND in the ventral striatum (VST), caudate (CAD), putamen (PUT). [11C]raclopride BPND was significantly reduced by 9.7 ± 4.4 %, 8.4 ± 4.2 % and 14.7 ± 4.8% following 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% following 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 to [11C]raclopride by a factor of 1.49 to 1.90, the same data for a related outcome measure binding potential, BPP, 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.
Footnotes
- Received November 9, 2009.
- Revision received January 21, 2010.
- Accepted January 25, 2010.
- The American Society for Pharmacology and Experimental Therapeutics