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(-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D2 receptor agonist and 11CNPA is a suitable radiotracer to image D2 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 11CNPA to acute fluctuation in synaptic DA was assessed with PET in baboons and compared to that of the reference D2 receptor antagonist radiotracer 11Craclopride. Three male baboons were studied with 11Craclopride and 11CNPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg(-1) i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific-to-nonspecific equilibrium partition coefficient (V3"). 11CRaclopride V3" was reduced by 24 +/- 10%, 32 +/- 6%, and 44 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. 11CNPA V3" was reduced by 32 +/- 2%, 45 +/- 3%, and 53 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. Thus, endogenous DA was more effective at competing with 11CNPA binding compared to 11Craclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, 11CNPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease.
Narendran et al. (Thu,) studied this question.