Monovalent and bivalent fibrin-specific MRI contrast agents for detection of thrombus
Monovalent and bivalent fibrin-specific MRI contrast agents for detection of thrombus
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DOI：
10.1002/anie.200800563
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Nair, Shrikumar A.;Kolodziej, Andrew E.;Caravan, Peter
中风、心脏病和肺栓塞等血栓栓塞疾病极大地增加了发达国家的医疗费用。许多成像技术（超声波、磁共振成像 (MRI)、伽玛闪烁扫描、计算机断层扫描）用于识别血栓，首选技术通常取决于解剖区域。然而，这些方法通常无法区分血栓与其他病变（例如动脉粥样硬化斑块、肿瘤）。如果有一种单一的三维成像方式可以对全身血栓栓塞性疾病提供特异性和灵敏的诊断，那么纤维蛋白是一种有用的 MR 靶点，因为它是动脉和静脉血栓的主要蛋白质成分，在血栓中的浓度为 10–100 μm，该浓度范围与钆造影剂的检测相容。[1, 2] 与含钆纳米粒子连接的纤维蛋白特异性抗体已成功用于在动物模型中使用 MRI 检测血栓。[3, 4] EP-2104R 是一种由四种 Gd 螯合物衍生的纤维蛋白特异性肽，已在多种动物血栓模型中显示出 MR 成像功效。[5-9] 在此，我们报告了一种对纤维蛋白具有特异性的新肽序列，并比较了单价和二价纤维蛋白特异性多聚 MRI 的纤维蛋白结合和弛豫特性造影剂。体内数据证明了二价药物在静脉血栓形成模型中的定位。
Thromboembolic diseases such as stroke, heart attack, and pulmonary embolism contribute significantly to the cost of healthcare in the developed world. Many imaging techniques (ultrasound, magnetic resonance imaging (MRI), gamma scintigraphy, computed tomography) are used to identify thrombus, and the preferred technique often depends on the anatomical region. However these methods typically cannot distinguish thrombus from other pathologies (eg atherosclerotic plaque, tumor). It would be useful to have a single, three-dimensional imaging modality that can provide a specific and sensitive diagnosis of thromboembolic disease over the whole body.Fibrin is a useful MR target because it is the major protein constituent of arterial and venous clots and is present at 10–100 μm in the thrombus, a concentration range compatible with detection by gadolinium-based contrast agents.[1, 2] Fibrin-specific antibodies linked to gadolinium-containing nanoparticles have been successfully used to detect thrombi using MRI in animal models.[3, 4] EP-2104R, a fibrin-specific peptide derivatized with four Gd chelates, has shown MR imaging efficacy in a variety of animal thrombus models.[5–9] Herein we report a new peptide sequence with specificity for fibrin and a comparison of the fibrin-binding and relaxivity properties of monovalent and bivalent fibrin-specific multimeric MRI contrast agents. In vivo data are presented that demonstrate localization of the bivalent agent in a model of venous thrombosis.