Chefer Svetlana, Thomasson David, Seidel Jurgen, Reba Richard C, Bohannon J Kyle, Lackemeyer Mathew G, Bartos Chris, Sayre Philip J, Bollinger Laura, Hensley Lisa E, Jahrling Peter B, Johnson Reed F
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
EJNMMI Res. 2015 Dec;5(1):65. doi: 10.1186/s13550-015-0143-x. Epub 2015 Nov 16.
The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K i ) in responsive lymphoid tissue.
Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K i for lymphoid tissues by Patlak plot.
Two-way repeated measures analysis of variance revealed alterations in K i that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K i changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K i was observed in mediastinal lymph nodes (LNs) that correlated to K i changes in axillary LNs. Changes in LNs K i were concurrent with elevations of monocytes in peripheral blood.
[(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus.
中东呼吸综合征（MERS）由最近发现的冠状病毒MERS-CoV引起，由于目前尚无合适的动物模型，其发病机制和免疫反应尚未完全明确。氟代脱氧葡萄糖（18F-FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）作为一种纵向非侵入性方法，有助于提供宿主免疫反应的生物标志物。在病毒入侵后，活化免疫细胞中18F-FDG摄取增加，可通过PET成像定位。我们使用18F-FDG-PET/CT研究非人灵长类动物暴露于MERS-CoV后宿主反应的发展，并应用动力学模型监测反应性淋巴组织中的流入速率常数（Ki）。
在一台改装为可在生物安全4级环境中运行的PET/CT临床扫描仪上，在MERS-CoV气溶胶暴露前及暴露后长达29天采集多张18F-FDG-PET和CT图像。重建各种淋巴组织的时间-活性曲线，以跟踪18F-FDG摄取约60分钟（3600秒）。利用图像衍生输入函数通过Patlak图计算淋巴组织的Ki。
双向重复测量方差分析显示，Ki的变化与病毒暴露后的时间点（p<0.001）和淋巴组织位置（p=0.0004）有关。这两个因素之间存在统计学显著交互作用（p<0.0001），表明三个位置的Ki随时间变化的模式不同，但不同个体之间无差异。在纵隔淋巴结（LNs）中观察到Ki有显著统计学意义的升高模式，与腋窝LNs中的Ki变化相关。LNs中Ki的变化与外周血中单核细胞的升高同时出现。
18F-FDG-PET能够检测宿主对亚临床病毒感染的免疫反应中的细微变化。对于检测对病毒的免疫反应，完全定量分析是首选方法，而非使用标准化摄取值的半定量分析。
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