Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI
Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI
复制标题
DOI：
10.1073/pnas.0606281104
复制
发表时间：
2007-01-16
影响因子：
11.1
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Amirbekian, Vardan;Lipinski, Michael J.;Fayad, Zahi A.
我们研究了靶向免疫胶束在体内使用MRI检测和评估动脉粥样硬化斑块中巨噬细胞的能力。临床上需要一种从分子和细胞角度评估动脉粥样硬化的非侵入性工具。巨噬细胞在动脉粥样硬化中起中心作用，并与易破裂的斑块相关。因此，巨噬细胞清道夫受体(MSR)被选为分子磁共振的靶点。在ApoE-/-和WT小鼠身上用活体MRI检测MSR靶向免疫胶束、胶束和Gd-二乙基三氨基五乙酸(DTPA)。共聚焦激光扫描显微镜共定位，巨噬细胞免疫染色和MRI相关性，竞争抑制，以及各种其他分析。体内MRI显示，在注射24小时后，免疫胶束使ApoE-/-小鼠动脉粥样硬化的信号强度增加了79%，而使用非靶向胶束的只有34%，使用Gd-DTPA没有增强。激光共聚焦扫描显微镜显示斑块内荧光免疫胶束与巨噬细胞共存。动脉粥样硬化斑块中巨噬细胞的含量与体内匹配的MRI结果有很强的相关性，通过归一化百分比增强率来衡量。抗MSR的单抗能够显著阻碍免疫胶束在体内提供动脉粥样硬化血管的对比剂增强。免疫胶束在体内有效地增强了动脉粥样硬化斑块。所见强化与动脉粥样硬化血管区域的巨噬细胞含量有关。免疫胶束可能有助于检测与斑块易破裂相关的高巨噬细胞含量。
We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.