Dopamine D1 Receptor Imaging in the Rodent and Primate Brain Using the Isoquinoline (+)-[11C]A-69024 and Positron Emission Tomography

In vivo pharmacokinetic and brain binding characteristics of (+)-[11C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and β-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[11C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[11C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive (±)A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[11C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography.