MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor
MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor
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DOI：
10.1002/mrm.20995
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Lipinski, Michael J.;Amirbekian, Vardan;Fayad, Zahi A.
对巨噬细胞进行特异性成像的能力可以改善动脉粥样硬化的检测和表征。在本研究中，我们评估了小鼠巨噬细胞对含钆 (Gd) 的免疫胶束（与巨噬细胞特异性抗体相连的胶束）、胶束和标准造影剂的体外摄取，并试图确定免疫胶束和胶束是否改善载脂蛋白 E 敲除 (ApoE KO) 小鼠动脉粥样硬化的离体成像。将小鼠 RAW 264.7 巨噬细胞与 Gd-DTPA、胶束和免疫胶束一起孵育。使用具有反转恢复自旋回波序列的 1.5 T MR 系统制备细胞沉淀并成像，以确定体外 T-1 值。使用具有高空间分辨率序列 (78 x 39 x 78 mu m(3)) 的 9.4T MR 系统对小鼠主动脉进行离体分析。与 Gd-DTPA 相比，用胶束处理的细胞中 T-1 值显着降低（P < 0.0001），并且与胶束相比，用免疫胶束在 VC 下孵育的细胞中 T-1 值显着降低（P < 0.05）。与免疫胶束和胶束一起孵育的主动脉中，离体 MRI 信号强度 (SI) 分别显着增加 81% 和 20%。共聚焦显微镜证明了巨噬细胞在体外和离体体内摄取荧光免疫胶束。免疫胶束和胶束改善了巨噬细胞的体外和离体 MR 检测，并且可能在检测富含巨噬细胞的斑块中有用。
The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T-1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78 x 39 x 78 mu m(3)). The T-1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P < 0.0001), and in cells incubated at VC with immunomicelles compared to micelles (P < 0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.