Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation
Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation
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DOI：
10.1021/bc060018k
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Louie, AY
中科院分区：
文献类型：
--
作者：
Gustafsson, B;Youens, S;Louie, AY
在美国，动脉粥样硬化是导致死亡的主要原因。由于通过早期诊断有可能预防冠状动脉和动脉疾病，因此需要使用各种非侵入性技术（包括磁共振成像（MRI））对亚临床阶段和临床阶段的动脉进行成像的方法。我们描述了一种新的MRI造影剂的发展，针对斑块，将允许病变形成的成像。造影剂直接作用于巨噬细胞，巨噬细胞是形成斑块的最早成分之一。使用衍生自清道夫受体配体的MRI造影剂，通过巨噬细胞清道夫受体A（巨噬细胞特异性细胞表面蛋白）标记巨噬细胞。我们已经合成并表征了这些造影剂的弛豫范围。体外研究表明，靶向造影剂在巨噬细胞中积累，溶液研究表明微摩尔浓度足以在MR图像中产生对比。细胞毒性和初始生物分布研究表明毒性低，在正常血管中没有可检测到的滞留，并且从血液中快速清除。这种造影剂针对血管炎症的良好性能为使用MRI跟踪其他炎症性疾病（如肿瘤免疫治疗和移植接受）打开了大门。
Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial disease through early diagnosis, there is a need for methods to image arteries in the subclinical stage as well as clinical stage using various noninvasive techniques, including magnetic resonance imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages, and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted toward vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI.