McAteer Martina A, von Zur Muhlen Constantin, Anthony Daniel C, Sibson Nicola R, Choudhury Robin P
Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
Methods Mol Biol. 2011;680:103-15. doi: 10.1007/978-1-60761-901-7_7.
For molecular magnetic resonance imaging (mMRI), microparticles of iron oxide (MPIO) create potent hypointense contrast effects that extend a distance far exceeding their physical size. The potency of the contrast effects derive from their high iron content and are significantly greater than that of ultra-small particles of iron oxide (USPIO), commonly used for MRI. Due to their size and incompressible nature, MPIO are less susceptible to nonspecific vascular egress or uptake by endothelial cells. Therefore, MPIO may be useful contrast agents for detection of endovascular molecular targets by MRI. This Chapter describes the methodology of a novel, functional MPIO probe targeting vascular cell adhesion molecule-1 (VCAM-1), for detection of acute brain inflammation in vivo, at a time when pathology is undetectable by conventional MRI. Protocols are included for conjugation of MPIO to mouse monoclonal antibodies against VCAM-1 (VCAM-MPIO), the validation of VCAM-MPIO binding specificity to activated endothelial cells in vitro, and the application of VCAM-MPIO for in vivo targeted MRI of acute brain inflammation in mice. This functional molecular imaging tool may potentially accelerate accurate diagnosis of early cerebral vascular inflammation by MRI, and guide specific therapy.
对于分子磁共振成像（mMRI），氧化铁微粒（MPIO）可产生强烈的低信号对比效应，其作用范围远远超过其物理尺寸。这种对比效应的强度源于其高铁含量，且显著大于常用于MRI的超小氧化铁颗粒（USPIO）。由于其尺寸和不可压缩的性质，MPIO较不易发生非特异性血管逸出或被内皮细胞摄取。因此，MPIO可能是用于通过MRI检测血管内分子靶点的有用对比剂。本章描述了一种新型功能性MPIO探针的方法，该探针靶向血管细胞黏附分子-1（VCAM-1），用于在传统MRI无法检测到病理变化时在体内检测急性脑炎症。其中包括MPIO与抗VCAM-1小鼠单克隆抗体（VCAM-MPIO）偶联的方案、VCAM-MPIO体外与活化内皮细胞结合特异性的验证，以及VCAM-MPIO在小鼠急性脑炎症体内靶向MRI中的应用。这种功能性分子成像工具可能会加速通过MRI对早期脑血管炎症的准确诊断，并指导特异性治疗。
