Synthesis and in vivo evaluation of a new fluorine‐18 labeled dopamine D2 radioligand synthesis with benzofuran benzamide skeleton

N‐[(1‐Ethyl‐2‐pyrrolidinyl)methyl]‐5‐(2‐[¹⁸F]fluoroethyl)‐2,3‐dihydroben‐zofuran‐7‐carboxamide ([¹⁸F]5) was synthesized via nucleophilic substitution with K¹⁸F/Kryptofix222 complex in 5.4∼6.8% radiochemical yields with a specific activity of larger than 5.6 TBq/mmol (150 Ci/mmol) at the end of the 110 minutes synthetic period. Its in vivo affinity toward CNS dopamine D2 receptors was investigated using rats in order to evaluate as a radiotracer for the PET (positron emission tomography) study of the dopamine D2 receptors. In biodistribution experiments, [¹⁸F]5 exhibited striatal accumulation, although the whole brain radioactivity was cleared rapidly. The striatal/cerebellar radioactivity ratio, which corresponds to the ratio of a brain D2 receptor‐rich to poor region, gradually increased to about 12 at 60 minutes after the injection. The striatal uptake was inhibited with pretreated haloperidol, a dopamine D2 antagonist, indicating that the striatal accumulation was due to the specific binding with D2 receptors. Thus, [¹⁸F]5 appears to be a potential in vivo radiotracer for dopamine D2 receptors.