Selective DAAO inhibitors have demonstrated promising therapeutic effects in clinical studies, including clinically alleviating symptoms of schizophrenic patients and ameliorating cognitive function in Alzheimer’s patients with early phase. Herein we report the synthesis and preliminary evaluation of a ¹¹C-labeled positron emission tomography ligand based on a DAAO inhibitor, DAO-1903 (8). ¹¹C-Isotopologue of 8 was prepared in high radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/µmol). In vitro autoradiography studies indicated that the ligand possessed high in vitro specific binding to DAAO, while in vivo dynamic PET studies demonstrated that [¹¹C]8 failed to cross the blood–brain barrier possibly due to moderate brain efflux mechanism. Further chemical scaffold optimization is necessary to overcome limited brain permeability and improve specific binding.

选择性 DAAO 抑制剂已在临床研究中显示出有希望的治疗效果，包括临床缓解精神分裂症患者的症状和改善早期阿尔茨海默病患者的认知功能。在此，我们报告了基于 DAAO 抑制剂 DAO-1903 ( 8 )的¹¹ C 标记正电子发射断层扫描配体的合成和初步评估。以高放射化学收率、高放射化学纯度 (>99%) 和高摩尔活性 (>37 GBq/µmol) 制备了8 的¹¹ C-同位素体。体外放射自显影研究表明，该配体在体外对 DAAO具有高特异性结合，而在体内动态 PET 研究表明 [ ¹¹ C] 8未能穿过血脑屏障可能是由于中等脑外流机制。需要进一步的化学支架优化来克服有限的大脑通透性并改善特异性结合。