Detection of vascular expression of e-selectin in vivo with MR imaging
Detection of vascular expression of e-selectin in vivo with MR imaging
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DOI：
10.1148/radiol.2412050490
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发表时间：
2006-11-01
期刊：
影响因子：
19.7
通讯作者：
Edwards, A. David
中科院分区：
文献类型：
--
作者：
Reynolds, Peter R.;Larkman, David J.;Edwards, A. David
目的：为了开发一种造影剂，用于靶向E-选择素表达在活化的血管内皮细胞和评估检测剂的磁共振（MR）成像在体内小鼠模型inflammation.Materials和方法：所有的动物实验批准根据动物福利和当地的伦理委员会的规定。将抗鼠E-选择素F（ab '）（2）单克隆抗体MES-1与超小超顺磁性氧化铁（USPIO）纳米颗粒缀合。通过使用表达小鼠E-选择素的中国仓鼠卵巢（CHO）细胞进行流式细胞术、铁的Perl普鲁士蓝染色和MR成像以检测缀合物的体外结合，并且使用耳中对恶唑酮的接触性超敏反应的小鼠模型来研究MES-1-USPIO的体内特征。使用9.4 T MR成像系统和定制的仅接收线圈进行序列成像。结果：MES-1-USPIO在体外可与表达小鼠E-选择素的CHO细胞结合。在体内注射MES-1-USPIO后，当与对照耳相比时，在发炎耳中检测到R2弛豫率（1/T2）特征的明显变化。组织学分析证实了MES-1-USPIO的血管内皮分布。结论：MR可选择性地、直接地无创性地显示E-选择素在体内的表达，这对炎症性疾病的研究具有潜在的应用价值。
Purpose: To develop a contrast agent for targeting E-selectin expressed on activated vascular endothelium and to evaluate detection of the agent with magnetic resonance (MR) imaging in an in vivo mouse model of inflammation.Materials and Methods: All animal experiments were approved according to animal welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')(2) monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells expressing mouse E-selectin to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was performed by using a 9.4-T MR imaging system with a custom receive-only coil. Tissue slices were stained to define distribution of E-selectin expression and localization of the MES-1-USPIO conjugate.Results: MES-1-USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were detected in inflamed ears when they were compared with control ears. Histologic analysis confirmed the vascular endothelial distribution of MES-1-USPIO.Conclusion: E-selectin expression in vivo can be selectively and directly imaged noninvasively with MR. This has the potential to be useful in the study of inflammatory disease.