在vivo中使用positron发射断层扫描对病毒和细菌病原体进行巨酶介导宿主免疫反应的成像
Apurva Pandey1, Shalini Chopra1, Simon J Cleary2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94158, United States.
ACS infectious diseases
|May 31, 2024
概括
研究人员开发了一种新的成像剂,[64Cu]Cu-GRIP B,以在体内可视化酶B的活性. 这种工具成功地检测到了小鼠对流感和细菌感染的granzyme B免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 分子成像学分子成像学
- 生物化学 生物化学
背景情况:
- 主体对病原体的免疫反应涉及复杂的机制,包括大酶在亡中的作用.
- 了解特定的大酶蛋白酶的体内动员对于开发向疗法至关重要.
- 限制相互作用 (RIPs) 是一种新型放射性药物,旨在用于积极内蛋白酶的正电子发射断层扫描 (PET) 成像.
研究的目的:
- 评价[64Cu]Cu-GRIP B,一种特定于granzyme B的RIP的实用性,用于在各种病原体感染期间体内成像granzyme B活性.
- 通过使用非侵入性PET成像来调查酶B在对流感和细菌病原体的宿主防御中的作用.
主要方法:
- 开发了由流感A病毒 (H1N1) 引起的肺炎和由各种细菌 (大肠杆菌,P. aeruginosa,K. pneumoniae,L. monocytogenes) 引起的肌肉炎的小鼠模型.
- 使用[64Cu]Cu-GRIP B用于体内微PET/CT成像和体外分析,包括玛计数和免疫组织化学.
- 对比野生型小鼠的成像结果与生殖系B大酶淘汰小鼠的成像结果.
主要成果:
- [64Cu]Cu-GRIP B PET/CT成像显示,与对照和Granzyme B淘汰赛小鼠相比,感染H1N1流感的野生型小鼠的肺部吸收量显著更高.
- 在细菌性肌炎模型中,[64Cu]Cu-GRIP B吸收在野生类型小鼠的感染肌肉中升高,但不是在大酶B淘汰赛小鼠中.
- 有趣的是,活生生的Listeria monocytogenes感染并没有通过PET诱导可检测的Granzyme B信号,这表明Granzyme B的潜在抑制作用.
结论:
- 这项研究表明,各种病原体引起的B蛋白酶活动可以在体内使用RIP [64Cu]Cu-GRIP B.有效地成像.
- 这种成像方法有助于在感染期间在体内生物学的granzyme B复合物的机械研究.
- 针对其他粒酶的RIP的未来发展将进一步增强对免疫蛋白酶 in vivo功能的理解.
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