Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge.
Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge.
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DOI：
10.1186/s13550-015-0143-x
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发表时间：
2015-12
期刊：
影响因子：
3.2
通讯作者：
Johnson RF
中科院分区：
文献类型：
--
作者：
Chefer S;Thomasson D;Seidel J;Reba RC;Bohannon JK;Lackemeyer MG;Bartos C;Sayre PJ;Bollinger L;Hensley LE;Jahrling PB;Johnson RF
中东呼吸综合征（MERS）的发病机制和免疫反应引起的最近发现的冠状病毒，MERS-CoV，还没有得到充分的表征，因为一个合适的动物模型，目前还没有。18 F-氟脱氧葡萄糖（[18 F]-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，可有益于提供宿主免疫反应的生物标志物。[18F]-FDG摄取在激活的免疫细胞中响应于病毒进入而增加，并且可以通过PET成像进行定位。我们使用[18 F]-FDG-PET/CT研究MERS-CoV暴露后非人灵长类动物中发生的宿主反应，并应用动力学建模来监测反应性淋巴组织中的流入速率常数（Ki）。在MERS-CoV气溶胶暴露前和暴露后29天内，在经改良的PET/CT临床扫描仪上采集多个[18 F]-FDG-PET和CT图像，以在生物安全性4级环境中运行。重建各种淋巴组织的时间活性曲线，以跟踪[18 F]-FDG摄取约60 min（3，600 s）。使用图像衍生的输入函数通过Patlak图计算淋巴组织的Ki。双向重复测量方差分析显示Ki的改变与病毒暴露后的时间点（p < 0.001）和淋巴组织的位置（p = 0.0004）相关。如这两个因素之间的统计学显著交互作用（p < 0.0001）所揭示的，Ki随时间变化的模式在三个位置之间不同，但在受试者之间不相同。在纵隔淋巴结（LN）中观察到Ki统计学显著升高的显著模式，其与腋窝LN中的Ki变化相关。LN Ki的变化与外周血单核细胞的升高同时发生。[18F]-FDG-PET能够检测宿主免疫反应的细微变化，以遏制亚临床病毒感染。全定量分析是首选方法，而不是使用标准化摄取值的半定量分析，用于检测对病毒的免疫应答。本文的在线版本（doi：10.1186/s13550-015-0143-x）包含补充材料，可供授权用户使用。
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. 18F-Fluorodeoxyglucose ([18F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [18F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [18F]-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 (Ki) in responsive lymphoid tissue. Multiple [18F]-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 [18F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate Ki for lymphoid tissues by Patlak plot. Two-way repeated measures analysis of variance revealed alterations in Ki 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 Ki changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in Ki was observed in mediastinal lymph nodes (LNs) that correlated to Ki changes in axillary LNs. Changes in LNs Ki were concurrent with elevations of monocytes in peripheral blood. [18F]-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. The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.