D₂-Dopamine receptor specific brain uptake of carbon-11-labeled YM-09151-2

The in vivo D₂-receptor specific brain uptake of N-[(2RS,3RS)-1-benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-[ ¹¹C]methylaminobenzamide([¹¹C]YM-09151-2), was investigated. In rat brain the high uptake of [¹¹C]YM-09151-2 in striatum was displaced with sulpiride spiroperidol, and YM-09151-2. SCH-23390 and ritanserin, D₁-dopamine and S₂-serotonin antagonists, showed no effect on the distribution of [¹¹C]YM-09151-2. In the striatum at 60 min, 95% of the radioactivity was detected as [¹¹C]YM-09151-2 by high performance liquid chromatography. On the other hand, 41% of ¹¹C in the plasma at 60 min was observed as metabolites. In vivo autoradiography showed a high uptake of [¹¹C]YM-09151-2 in the striatum and in the nucleus accumbens of rat brain. A high uptake of radioactivity was also found in the canine basal ganglia with positron emission tomography. The uptake was reduced by pretreatment with spiroperidol. The present results demonstrate that [¹¹C]YM-09151-2 is a D₂ receptor specific compound and is a potential in vivo tracer for measuring D₂ receptors.