Huang Guolong, Qiu Yifan, Bi Lei, Wei Huiyi, Li Guocong, Li Zhijun, Ye Peizhen, Yang Min, Shen Yanfang, Liu Hao, Wang Lu, Jin Hongjun
Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai519000, Guangdong, China.
Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou510630, China.
ACS Chem Neurosci. 2022 Dec 7;13(23):3464-3476. doi: 10.1021/acschemneuro.2c00506. Epub 2022 Nov 28.
The P2X7 receptor (P2X7R) is a key neuroinflammation target in a variety of neurodegenerative diseases. Improved radiosynthesis was developed according to the previously reported P2X7R antagonist GSK1482160. Biodistribution, radiometabolite, and dynamic positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT-MRI) of the lipopolysaccharide (LPS) rat model and the transgenic mouse model of Alzheimer's disease (AD) revealed a stable, low uptake of in the brain of healthy rats but a higher standardized uptake value ratio (SUVR) in LPS-treated rats (1.316 ± 0.062, = 3) than in sham (1.093 ± 0.029, = 3). There were higher area under curves (AUCs) in the neocortex (25.12 ± 1.11 vs 18.94 ± 1.47), hippocampus (22.50 ± 3.41 vs 15.90 ± 1.59), and basal ganglia (22.26 ± 0.81 vs 15.32 ± 1.76) of AD mice ( = 3) than the controls ( = 3) ( < 0.05). Furthermore, 50 min dynamic PET in healthy nonhuman primates (NHPs) indicated could penetrate the blood-brain barrier (BBB). In conclusion, from this study is a potent P2X7R PET tracer that warrants further neuroinflammation quantification in human studies.
P2X7受体（P2X7R）是多种神经退行性疾病中的关键神经炎症靶点。根据先前报道的P2X7R拮抗剂GSK1482160开发了改进的放射性合成方法。脂多糖（LPS）大鼠模型和阿尔茨海默病（AD）转基因小鼠模型的生物分布、放射性代谢物以及动态正电子发射断层扫描/计算机断层扫描 - 磁共振成像（PET/CT - MRI）显示，健康大鼠脑中的摄取稳定且低，但LPS处理的大鼠（n = 3）的标准化摄取值比率（SUVR）高于假手术组（n = 3）（1.316 ± 0.062比1.093 ± 0.029）。AD小鼠（n = 3）的新皮层（25.12 ± 1.11对18.94 ± 1.47）、海马体（22.50 ± 3.41对15.90 ± 1.59）和基底神经节（22.26 ± 0.81对15.32 ± 1.76）的曲线下面积（AUC）高于对照组（n = 3）（P < 0.05）。此外，健康非人灵长类动物（NHP）的50分钟动态PET表明该示踪剂可穿透血脑屏障（BBB）。总之，本研究中的该示踪剂是一种有效的P2X7R PET示踪剂，值得在人体研究中进一步进行神经炎症定量分析。
