糖原合成激酶-3β（GSK-3β）的失调涉及许多人类疾病，特别是在神经退行性疾病和精神类疾病的发病机理中起重要作用。发展靶向GSK-3β的正电子发射断层扫描（PET）显像剂可以活体内无创伤性定量检测GSK-3β的活性。本课题组前期研究发现了一种[18F]标记的马来酰亚胺结构GSK-3β显像剂具有高亲和性并且在大鼠脑部中度摄取。在此基础上，我们提出设想：[18F]标记马来酰亚胺结构抑制剂是有前景的GSK-3β PET显像剂。本课题以GSK-3β与马来酰亚胺抑制剂复合物的晶体结构为基础，用Autodock软件设计系列含氟乙基的马来酰亚胺结构GSK-3β抑制剂，合成、体外评估抑制剂筛选出高亲和力的潜在PET显像剂，[18F]标记得到GSK-3β PET显像剂并在啮齿类和非人灵长类动物体内进行PET显像，有望筛选出一种新型的GSK-3β PET显像剂用于脑疾病显像。

Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated numerous human diseases, particularly in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a non-invasive imaging technique would quantify detection of enzyme’s activity. Prior work from our laboratories has demonstrated a [18F]-labeled maleimide GSK-3β PET tracer with potent binding and moderate brain uptake in rodents. Therefore, we propose that the [18F]-labeled maleimides inhibitors could be as promising GSK-3β PET tracers. Herein, we will design a series of incorporating a fluoroethyl group in maleimides as GSK-3β inhibitors using Autodock software, based on the co-crystal structure of GSK-3β and maleimide inhibitor. These inhibitors will be synthesized and biological evaluated in vitro for screening potential PET tracers with potent binding. The [18F]-labeled GSK-3β tracers will be radiolabeled with [18F] and imaged in rodents and nonhuman primates with PET. It's promising to get a [18F]-labeled GSK-3β PET tracer for cerebral diseases imaging.