Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI.
Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI.
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DOI：
10.1002/cmmi.384
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发表时间：
2010-09
影响因子：
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通讯作者：
C. von zur Muhlen;A. Fink-Petri;J. Salaklang;D. Paul;I. Neudorfer;V. Berti;A. Merkle;K. Peter;C. Bode;D. von Elverfeldt
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作者：
C. von zur Muhlen;A. Fink-Petri;J. Salaklang;D. Paul;I. Neudorfer;V. Berti;A. Merkle;K. Peter;C. Bode;D. von Elverfeldt
巨噬细胞与超顺磁性氧化铁颗粒（SPIO）的成像已被执行，以提高检测动脉粥样硬化斑块炎症在人类和小鼠的研究，通过分子磁共振成像（MRI）。由于单核细胞/巨噬细胞整合素MAC-1（CD11b/CD18）的亲和力在炎症中上调，我们产生了一种靶向CD11b（CD11b-SPIO）的造影剂，用于改善斑块中的巨噬细胞检测。将CD11b-SPIO和非靶向SPIO（对照SPIO）与人单核细胞/巨噬细胞体外孵育。如通过SPIO诱导的MRI信号消退所定量的，在体外用CD11b-SPIO孵育的单核细胞/巨噬细胞中的细胞内铁含量显著高于用对照-SPIO孵育的单核细胞/巨噬细胞（p <0.05），表明CD11b-SPIO进入单核细胞的摄取得到改善。因此，使用9.4 T动物MRI系统，在注射CD11b-SPIO或对照SPIO造影剂之前和之后48 h，对采用西式饮食的ApoE（-/-）基因敲除小鼠的主动脉弓（AA）和血管分支进行成像。定量SPIO诱导的MRI信号变化，以及通过抗CD68免疫组化测定巨噬细胞含量和通过普鲁士蓝染色测定铁含量。然而，SPIO诱导的体内MRI信号消退在CD11b-SPIO和对照SPIO注射动物中相似，锁骨下动脉和AA亚段中CD11b-SPIO摄取改善的趋势不显著。这些数据与通过组织学获得的结果良好相关。尽管体外MRI数据表明单核细胞/巨噬细胞中靶向CD11b-SPIO的摄取增加，但与非靶向SPIO相比，体内小鼠数据不允许改善动脉粥样硬化斑块检测。因此，单核细胞/巨噬细胞的CD11b靶向MRI造影剂标记似乎不是稳定动脉粥样硬化斑块中的成功策略，例如在ApoE（-/-）-敲除模型中发现的。然而，MRI和组织学数据之间令人印象深刻的相关性鼓励进一步开发炎症和斑块特异性造影剂用于易损斑块成像。
Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC-1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b-SPIOs) for improved macrophage detection in plaques. CD11b-SPIOs and non-targeted SPIOs (control-SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO-induced MRI signal extinction, intracellular iron-content was significantly higher in monoytes/macrophages incubated with CD11b-SPIO than with control-SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b-SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE(-/-)-knockout mice on a Western-type diet were imaged before and 48 h after contrast agent injection of either CD11b-SPIOs or control-SPIOs, using a 9.4 T animal MRI system. The SPIO-induced change in the MRI signal was quantified, as well as the macrophage-content by anti-CD68 immunhistochemistry and the iron-content by Prussian-blue staining. However, SPIO-induced signal extinction in in vivo-MRI was similar in CD11b-SPIO and control-SPIO-injected animals, with a non-significant trend towards an improved uptake of CD11b-SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI-data indicated an increased uptake of targeted CD11b-SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non-targeted SPIOs. Therefore, CD11b-targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE(-/-)-knockout-model. However, the impressive correlation between MRI and histology data encourages further development of inflammation- and plaque-specific contrast agents for vulnerable plaque imaging.