In vivo vulnerability to competition by endogenous dopamine:: Comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11I]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride
In vivo vulnerability to competition by endogenous dopamine:: Comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11I]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride
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DOI：
10.1002/syn.20013
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发表时间：
2004-06-01
期刊：
影响因子：
2.3
通讯作者：
Laruelle, M
中科院分区：
文献类型：
--
作者：
Narendran, R;Hwang, DR;Laruelle, M
(-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D, receptor agonist and [C-11]NPA is a suitable radiotracer to image D-2 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 DA was assessed with PET in baboons and compared to that of the reference D, receptor antagonist radiotracer [C-11]raclopride. Three male baboons were studied with [C-11]raclopride and [C-11]NPA 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 (V-3"). [C-11]Raclopride V-3" 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. [C-11]NPA V-3" 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 [C-11]NPA binding compared to [C-11]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D-2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [C-11]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease. (C) 2004 Wiley-Liss, Inc.
