Molecular imaging of macrophages in antherosclerotic plaques using bimodal PEG-micelles

Molecular imaging of macrophages in antherosclerotic plaques using bimodal PEG-micelles
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DOI:
10.1002/mrm.21315
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发表时间:
2007-12-01
影响因子:
3.3
通讯作者:
Fayad, Zahi A.
Fayad, Zahi A.
中科院分区:
医学3区
文献类型:
--
作者:
Mulder, Willem J. M.;Strijkers, Gustav J.;Fayad, Zahi A.

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聚乙二醇化,荧光,和顺磁性胶束开发。将胶束与巨噬细胞清道夫受体(MSR)特异性抗体缀合。动脉粥样硬化apoE-KO小鼠的腹部动脉瘤在静脉注射造影剂(CA)之前和之后24 h用T-1加权高分辨率MRI成像。在注射MSR靶向胶束的载脂蛋白E敲除(apoE-KO)小鼠中观察到明显的信号增强(SE)(高达200%),而注射非靶向胶束的小鼠的主动脉血管壁显示出很小的SE。为了允许离体主动脉的荧光显微镜和光学成像,通过在胶束冠中掺入量子点(013)或在胶束中掺入罗丹明脂质来使胶束发荧光。主动脉的紫外线(UV)照射允许识别具有高巨噬细胞含量的区域,而MSR靶向的罗丹明胶束可以用荧光显微镜检测到,并发现与巨噬细胞相关。总之,本研究表明,apoE-KO小鼠中的巨噬细胞可以通过分子MRI和光学方法在施用聚乙二醇化胶束CA后有效且特异性地检测。
Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The abdominal aortas of atherosclerotic apoE-KO mice were imaged with T-1-weighted high-resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (013) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR-targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA.