99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation.
99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation.
复制标题
Tc-99m 标记的抗 CD11b SPECT/CT 成像可检测与炎症密切相关的斑块不稳定
DOI：
10.1038/srep20900
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发表时间：
2016-02-15
影响因子：
4.6
通讯作者：
Shi H
中科院分区：
文献类型：
--
作者：
Liu G;Hu Y;Xiao J;Li X;Li Y;Tan H;Zhao Y;Cheng D;Shi H
预测特定动脉粥样硬化斑块破裂的风险仍然具有挑战性，这是与炎症密切相关的血栓触发因素。CD11b是炎症细胞中丰富的生物标志物，并不局限于单核细胞/巨噬细胞。在本研究中，我们制作了一种名为99mTc-MAG3-anti-CD11b的探针，用于单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）检测动脉粥样硬化斑块。选择ApoE敲除（ApoE−/−）小鼠建立动物模型，以C57BL/6J小鼠为对照。在ApoE−/−小鼠中发现了更高的CD11b+细胞募集、更高的CD11b表达和更严重的全身炎症状态。在离体荧光成像和体内显微spect /CT成像中，探针对Raw-264.7巨噬细胞以及动脉粥样硬化斑块内浸润的炎症细胞均显示出较高的体外亲和力和特异性，并通过离体平面伽马成像、Oil-Red-O染色和cd11b免疫组织化学染色证实了这一点。SPECT/CT图像上的放射性强度与斑块中CD11b的表达呈显著正相关。总之，本研究证明了抗cd11b抗体介导小鼠动脉粥样硬化斑块炎性白细胞无创SPECT/CT成像的可行性。这种成像策略可以识别有破裂风险的富含炎症的斑块，并评估炎症靶向治疗动脉粥样硬化的有效性。
It remains challenging to predict the risk of rupture for a specific atherosclerotic plaque timely, a thrombotic trigger tightly linked to inflammation. CD11b, is a biomarker abundant on inflammatory cells, not restricted to monocytes/macrophages. In this study, we fabricated a probe named as 99mTc-MAG3-anti-CD11b for detecting inflamed atherosclerotic plaques with single photon emission computed tomography/computed tomography (SPECT/CT). The ApoE-knockout (ApoE−/−) mice were selected to establish animal models, with C57BL/6J mice used for control. A higher CD11b+-cell recruitment with higher CD11b expression and more serious whole-body inflammatory status were identified in ApoE−/− mice. The probe showed high in vitro affinity and specificity to the Raw-264.7 macrophages, as well as inflammatory cells infiltrated in atherosclerotic plaques, either in ex vivo fluorescent imaging or in in vivo micro-SPECT/CT imaging, which were confirmed by ex vivo planar gamma imaging, Oil-Red-O staining and CD11b-immunohistochemistry staining. A significant positive relationship was identified between the radioactivity intensity on SPECT/CT images and the CD11b expression in plaques. In summary, this study demonstrates the feasibility of anti-CD11b antibody mediated noninvasive SPECT/CT imaging of inflammatory leukocytes in murine atherosclerotic plaques. This imaging strategy can identify inflammation-rich plaques at risk for rupture and evaluate the effectiveness of inflammation-targeted therapies in atheroma.