Brain region binding of the D 2/3 agonist [ 11 C]‐(+)‐PHNO and the D 2/3 antagonist [ 11 C]raclopride in healthy humans

The D 2 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. [ 11 C]‐(+)‐PHNO is a PET D 2 agonist radioligand and therefore provides a preferential measure of the D 2 high receptors. In contrast, [ 11 C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D 2 high‐ and low‐affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [ 11 C]‐(+)‐PHNO and [ 11 C]raclopride in volunteers using a within‐subject design. Both radioligands accumulated in brain areas rich in D 2 /D 3 ‐receptors. However, [ 11 C]‐(+)‐PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [ 11 C]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 [ 11 C]raclopride, equal in the ventral‐striatum (3.4 vs. 3.3), and higher in the globus pallidus for [ 11 C]‐(+)‐PHNO (1.8 vs. 3.3). Moreover [ 11 C]‐(+)‐PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [ 11 C]‐(+)‐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 D 3 ‐over‐D 2 with [ 11 C]‐(+)‐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. © 2007 Wiley‐Liss, Inc.