Novel MRI contrast agent for molecular imaging of fibrin implications for detecting vulnerable plaques
Novel MRI contrast agent for molecular imaging of fibrin implications for detecting vulnerable plaques
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DOI：
10.1161/hc3601.094303
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发表时间：
2001-09-11
期刊：
影响因子：
37.8
通讯作者：
Lanza, GM
中科院分区：
文献类型：
--
作者：
Flacke, S;Fischer, S;Lanza, GM
背景-易损动脉粥样硬化斑块裂隙内血栓的分子成像需要灵敏的血栓特异性造影剂检测。在这项研究中，我们报告了一种新型的配体靶向顺磁性分子成像剂的开发和表征，该分子成像剂具有对纤维蛋白的高亲和力和灵敏地检测活性易损斑块的潜力。方法和结果-纳米颗粒用2.5至50摩尔%的Gd-DTPA-BOA配制，其对应于>50 000 Gd 3+原子/颗粒。顺磁性纳米粒子的特点是在体外和体内评价。在对比传统的血池剂，T1弛豫速率作为顺磁性纳米粒子的数量的函数单调增加与Gd-DTPA浓度从0.18 mL。s（-1）. pmol（-1）（10% Gd-DTPA纳米颗粒）至0.54 mL。s（-1）. pmol（-1）。在体外与顺磁性纳米粒子靶向的血栓呈现出高度可检测的，均匀的T1加权对比增强，提高钆水平（0，2.5，和20摩尔% Gd）。更高分辨率的扫描和扫描电子显微镜显示，纳米颗粒作为薄层存在于凝块表面。在开放循环条件下，在体内对比度增强犬进行了评估。目标凝块和目标血管之间的对比噪声比（20 mol% Gd-DTPA纳米颗粒）与血液之间的比值约为118+/-21，靶向凝块与对照凝块之间的比值为131+/-37。结论-这些结果表明，纤维蛋白靶向顺磁性纳米颗粒的分子成像可以提供敏感的检测和纤维蛋白的定位，直接识别易损斑块，从而及早做出治疗决定。
Background-Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques.Methods and Results-The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd3+ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL . s(-1) . pmol(-1) (10% Gd-DTPA nanoparticles) to 0.54 mL . s(-1) . pmol(-1) for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was approximate to 118+/-21, and that between the targeted clot and the control clot was 131+/-37.Conclusions-These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.