Brain region binding of the D2/3 agonist [11C]‐(+)‐PHNO and the D2/3 antagonist [11C]raclopride in healthy humans

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Abstract
The D2 receptors exist in either the high‐ or low‐affinity state with respect to agonists, and while agonists bind preferentially to the high‐affinity state, antagonists do not distinguish between the two states. [11C]‐(+)‐PHNO is a PET D2 agonist radioligand and therefore provides a preferential measure of the D2high receptors. In contrast, [11C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D2 high‐ and low‐affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [11C]‐(+)‐PHNO and [11C]raclopride in volunteers using a within‐subject design. Both radioligands accumulated in brain areas rich in D2/D3‐receptors. However, [11C]‐(+)‐PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [11C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [11C]raclopride, equal in the ventral‐striatum (3.4 vs. 3.3), and higher in the globus pallidus for [11C]‐(+)‐PHNO (1.8 vs. 3.3). Moreover [11C]‐(+)‐PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [11C]‐(+)‐PHNO in the globus pallidus and ventral‐striatum could be the presence of a greater proportion of high‐ vs. low‐affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D3‐over‐D2 with [11C]‐(+)‐PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008.

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