ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo
ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo
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DOI：
10.1073/pnas.1518836113
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发表时间：
2016-02-23
影响因子：
11.1
通讯作者：
Wiehr, Stefan
中科院分区：
文献类型：
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作者：
Rolle, Anna-Maria;Hasenberg, Mike;Wiehr, Stefan
侵袭性肺曲霉病 (IPA) 是一种由烟曲霉引起的危及生命的肺部疾病，是血液恶性肿瘤和骨髓移植患者与侵袭性真菌感染相关的死亡率和发病率的主要原因。我们开发并测试了一种基于抗体引导的正电子发射断层扫描和磁共振（immunoPET/MR）成像的无创检测烟曲霉肺部感染的新型探针。将 [Cu-64] DOTA 标记的烟曲霉特异性单克隆抗体 (mAb) JF5 给予中性粒细胞耗尽的烟曲霉感染小鼠，与 PET 相结合，可以实现肺部感染的特异性定位。使用荧光染料标记的 mAb 进行的光学成像显示与侵入性菌丝共定位。基于 mAb 的新开发的 PET 示踪剂 [Cu-64] DOTA-JF5 可将 IPA 与细菌性肺部感染区分开来，并且与 [F-18] FDG-PET 相比，可将 IPA 与与肺部炎症相关的代谢活动普遍增加区分开来。据我们所知，这是首次将抗体引导的体内成像用于人类真菌性肺病（IPA）的无创诊断，这种方法在传染病诊断和临床转化方面具有巨大潜力。
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [Cu-64] DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [Cu-64] DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [F-18] FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation.