Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics , Chinese Academy of Sciences , Beijing 100101 , China.
Department of Nuclear Medicine, Zhongshan Hospital , Fudan University/Shanghai Institute of Medical Imaging , Shanghai 200032 , China.
ACS Nano. 2018 Sep 25;12(9):9300-9308. doi: 10.1021/acsnano.8b04158. Epub 2018 Sep 4.
Inflammation and calcification concomitantly drive atherosclerotic plaque progression and rupture and are the compelling targets for identifying plaque vulnerability. However, current imaging modalities for vulnerable atherosclerotic plaques are often limited by inadequate specificity and sensitivity. Here, we show that natural H-ferritin nanocages radiolabeled with technetium-99m (Tc-HFn) can identify and accurately localize macrophage-rich, atherosclerotic plaques in living mice using combined SPECT and CT. Focal Tc-HFn uptake was observed in the atherosclerotic plaques with multiple high-risk features of macrophage infiltration, active calcification, positive remodeling, and necrosis on histology and in early active ongoing lesions with intense macrophage infiltration. The uptake of Tc-HFn in plaques enabled quantitative measuring of the dynamic changes of inflammation during plaque progression and anti-inflammation treatment. This strategy lays the foundation of using bioengineered endogenous human ferritin nanocages for the identification of vulnerable and early active plaques as well as potential assessment of anti-inflammation therapy.
炎症和钙化共同驱动动脉粥样硬化斑块的进展和破裂，是识别斑块易损性的迫切靶点。然而，目前用于易损性动脉粥样硬化斑块的成像方式往往受到特异性和敏感性不足的限制。在这里，我们展示了用锝-99m（Tc-HFn）放射性标记的天然 H 铁蛋白纳米笼（Tc-HFn），可以使用 SPECT 和 CT 相结合的方式，在活体小鼠中识别和准确定位富含巨噬细胞的动脉粥样硬化斑块。在组织学上具有多个巨噬细胞浸润、活跃钙化、阳性重构和坏死等高危特征的动脉粥样硬化斑块上，以及在巨噬细胞浸润强烈的早期活动进行性病变中，观察到 Tc-HFn 的局部摄取。Tc-HFn 在斑块中的摄取使炎症在斑块进展和抗炎治疗过程中的动态变化能够进行定量测量。这项策略为使用生物工程化的内源性人铁蛋白纳米笼来识别易损性和早期活动性斑块以及潜在评估抗炎治疗奠定了基础。
