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Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

机译:免疫pET / mR成像允许体内特异性检测烟曲霉肺部感染

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摘要

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus , 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 lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging.Administration of a [Cu]DOTA-labeled-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted -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]DOTA-JF5 distinguishedIPA from bacterial lung infections and, in contrast to [F]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 non-invasive 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.
机译:侵袭性肺曲霉病(IPA)是由真菌引起的危及生命的肺部疾病,并且是血液系统恶性肿瘤和骨髓移植患者中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新型抗体,用于基于抗体导向的正电子发射断层扫描和磁共振成像(immunoPET / MR)的无创检测肺部感染。[Cu] DOTA标记的特异性单克隆抗体(mAb),JF5,当与PET结合时,对中性白细胞减少的感染小鼠进行肺部感染的特定定位。用荧光染料标记的mAb进行光学成像显示与侵入性菌丝共定位。基于mAb的最新开发的PET示踪剂[Cu] DOTA-JF5将IPA与细菌性肺部感染区分开,并且与[F] FDG-PET相比,将IPA与与肺部炎症相关的代谢活性普遍增加区分开来。据我们所知,这是首次将抗体引导的体内成像用于人类的真菌性肺病(IPA)的非侵入性诊断,这种方法在诊断感染性疾病和临床上具有巨大潜力翻译。

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