New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection
New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection
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DOI：
10.18632/oncotarget.7770
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发表时间：
2016-03-08
期刊：
影响因子：
--
通讯作者：
Autenrieth, Stella E.
中科院分区：
文献类型：
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作者：
Wiehr, Stefan;Warnke, Philipp;Autenrieth, Stella E.
肠杆菌科是人类革兰氏阴性细菌感染的最常见原因，其特异性和快速检测仍然是一个重大挑战。我们开发了一种非侵入性的方法来快速检测系统性小肠结肠炎耶尔森氏菌感染，使用免疫PET（抗体靶向正电子发射断层扫描）与[Cu-64] NODAGA标记的耶尔森氏菌特异性多克隆抗体靶向外膜蛋白YadA。与示踪剂[F-18]FDG相反，[Cu-64]NODAGA-YadA摄取以剂量依赖性方式与耶尔森氏菌感染小鼠的细菌病变共定位，如通过磁共振（MR）成像检测到的。在离体生物分布研究中，这伴随着感染组织中[Cu-64] NODAGA-YadA的摄取升高，而在用未标记的抗YadA抗体阻断后观察到摄取降低。我们首次展示了一种细菌特异性的、基于抗体的体内成像方法，用于诊断革兰氏阴性肠细菌感染，作为概念验证，这可能为病原体-宿主相互作用提供新的见解。
The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [Cu-64] NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [F-18]FDG, [Cu-64]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [Cu-64] NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions.