Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM, Utrecht, the Netherlands.
Mol Imaging Biol. 2013 Aug;15(4):411-22. doi: 10.1007/s11307-013-0617-z.
Magnetic resonance imaging (MRI) with targeted contrast agents provides a promising means for diagnosis and treatment monitoring after cerebrovascular injury. Our goal was to demonstrate the feasibility of this approach to detect the neuroinflammatory biomarker intercellular adhesion molecule-1 (ICAM-1) after stroke and to establish a most efficient imaging procedure.
We compared two types of ICAM-1-functionalized contrast agent: T 1-shortening gadolinium chelate-containing liposomes and T2(*)-shortening micron-sized iron oxide particles (MPIO). Binding efficacy and MRI contrast effects were tested in cell cultures and a mouse stroke model.
Both ICAM-1-targeted agents bound effectively to activated cerebrovascular cells in vitro, generating significant MRI contrast-enhancing effects. Direct in vivo MRI-based detection after stroke was only achieved with ICAM-1-targeted MPIO, although both contrast agents showed similar target-specific vascular accumulation.
Our study demonstrates the potential of in vivo MRI of post-stroke ICAM-1 upregulation and signifies target-specific MPIO as most suitable contrast agent for molecular MRI of cerebrovascular inflammation.
靶向对比剂的磁共振成像(MRI)为脑血管损伤后的诊断和治疗监测提供了一种很有前途的手段。我们的目标是证明这种方法检测卒中后神经炎症生物标志物细胞间黏附分子-1(ICAM-1)的可行性,并建立最有效的成像程序。
我们比较了两种类型的 ICAM-1 功能化对比剂:T1 缩短型含钆螯合物的脂质体和 T2(*)-缩短型微米级氧化铁颗粒(MPIO)。在细胞培养和小鼠卒中模型中测试了结合效力和 MRI 对比效果。
两种 ICAM-1 靶向试剂在体外均能有效地与激活的脑血管细胞结合,产生显著的 MRI 对比增强效果。尽管两种对比剂均显示出类似的靶向血管蓄积,但只有 ICAM-1 靶向 MPIO 可直接在卒中后进行体内 MRI 检测。
我们的研究证明了卒中后 ICAM-1 上调的体内 MRI 检测的潜力,并表明靶向特异性 MPIO 是脑血管炎症的分子 MRI 最适合的对比剂。