Department of Radiology-Medical Physics, University Medical Center Freiburg, Germany.
Contrast Media Mol Imaging. 2012 Mar-Apr;7(2):204-13. doi: 10.1002/cmmi.482.
The development of magnetic resonance imaging (MRI) contrast agents targeting epitopes in atherosclerosis is of general interest. In particular, early detection of activated platelets as key players in plaque rupture could provide improved triage of patients. However, so far the efficiency of contrast agents targeting human pathologies can only be examined in animal experiments, which do not necessarily reflect human in vivo conditions. We therefore describe application of a contrast agent targeting activated human platelets in an MRI tissue flow chamber, allowing detection and characterization of contrast agent binding. Microparticles of iron oxide (MPIO) were conjugated to an antibody targeting ligand-induced binding sites (LIBS) on the activated platelet glycoprotein IIb/IIIa-receptor or to control antibody, resulting in LIBS-MPIO or control-MPIO contrast agent. Human endarterectomy specimens from patients with acute stroke or transient ischemic attack were imaged ex vivo before and after contrast agent perfusion using a 9.4 T MRI system. Specimens were measured under static (n = 18) or flow conditions (n = 18) in a specially designed flow chamber setup, simulating physiological conditions in a stenosed vessel. A significant MPIO-induced negative contrast was achieved in MRI by LIBS-MPIO in specimens under static and flow conditions (LIBS-MPIO vs control-MPIO: p < 0.01), and the location of LIBS-MPIO binding corresponded well between histology and MRI (p < 0.05). The number of MPIOs per platelet area on endarterectomy specimens in histology was significantly higher with LIBS-MPIO (p < 0.001). Furthermore, the intensity of contrast agent binding and signal change showed the potential to reflect the severity of clinical symptoms. LIBS-MPIO allows the detection of activated platelets on the surface of symptomatic atherosclerotic human plaques using molecular MRI. Furthermore, the MRI tissue flow chamber setup described could help to evaluate binding properties of contrast agents, and might therefore be an interesting tool for contrast agent development from animal experiments towards clinical application.
针对动脉粥样硬化表位的磁共振成像（MRI）对比剂的开发受到普遍关注。特别是，作为斑块破裂关键因素的激活血小板的早期检测可以为患者的分诊提供更好的选择。然而，到目前为止，针对人类病理的对比剂的效率只能在动物实验中进行检查，而动物实验并不一定反映人体的体内情况。因此，我们描述了在 MRI 组织流动室中应用靶向激活人血小板的对比剂的方法，允许检测和表征对比剂结合。氧化铁（MPIO）微球与针对激活血小板糖蛋白 IIb/IIIa 受体配体诱导结合位点（LIBS）的抗体或对照抗体缀合，导致 LIBS-MPIO 或对照-MPIO 对比剂。使用 9.4 T MRI 系统，对来自急性中风或短暂性脑缺血发作患者的人类内膜切除术标本进行对比剂灌注前后的离体成像。标本在专门设计的流动室设置下在静态（n=18）或流动条件下（n=18）进行测量，模拟狭窄血管中的生理条件。LIBS-MPIO 在静态和流动条件下的 MRI 中产生了显著的 MPIO 诱导的负对比（LIBS-MPIO 与对照-MPIO：p<0.01），并且 LIBS-MPIO 结合的位置在组织学和 MRI 之间很好地对应（p<0.05）。组织学上，LIBS-MPIO 标记的内膜切除术标本上的血小板面积的 MPIO 数量明显更高（p<0.001）。此外，对比剂结合的强度和信号变化具有反映临床症状严重程度的潜力。LIBS-MPIO 允许使用分子 MRI 检测有症状的动脉粥样硬化人类斑块表面的激活血小板。此外，所描述的 MRI 组织流动室设置可帮助评估对比剂的结合特性，因此可能是将对比剂从动物实验开发到临床应用的有趣工具。
Am J Physiol Heart Circ Physiol. 2012-10-12
Zotero 插件