In vivo evaluation of 11C-labeled 2-arylpropionic acid as a PET probe for COXs in neuroinflammation

为了开发体内监测COXs活性和/或表达的显像剂，我们用11C标记了一系列NSAIDs的2-芳基丙酸衍生物。其中，我们发现^<11> c标记的酮洛芬甲酯（KTP-Me），其酸形态对COX-1具有特异性，对大鼠脑炎症表现出优越的敏感性。此外，我们的研究结果表明^<11> C-KTP-Me识别了脑内COX-1表达的变化，为小胶质细胞激活的特异性成像提供了新的证据。在猴子的PET研究中也发现了^<11 b>的C-KTP-Me在神经炎症区域的高积累。^<11> C-KTP-Me在大鼠和猴子体内的安全性、生物分布和动力学表明，它可以用于人体研究。

In order to develop the imaging agent for the in vivo monitoring of COXs activity and/or expression, a series of 2-arylpropionic acid derivatives of NSAIDs were labeled with 11C. Among them, we found that^<11> C-labeled ketoprofen-methyl ester(KTP-Me), its acid form rather specific to COX-1, showed superior sensitivity to inflammation of rat brain. In addition, our results suggest that^<11> C-KTP-Me recognize the changes of COX-1 expression in brain, and provide new evidence for the specific imaging of microglial activation. PET study in monkeys also showed the high accumulation of^<11> C-KTP-Me in neuroinflammatory area. The safety, biodistribution and kinetics of^<11> C-KTP-Me in both rats and monkeys indicate that it should be acceptable for the use of study in human.