Division of Vascular Surgery, Department of Surgery (K.-U.J., J.Y., Y.K., V.N., A.M.F., P.T., Y.W., A.V.E., M.L., M.K., N.J.L.), Stanford University School of Medicine, CA.
Department of Pathology, The University of Alabama at Birmingham (V.N.).
Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2821-2828. doi: 10.1161/ATVBAHA.120.315239. Epub 2020 Oct 22.
This study sought to determine whether F-fluorodeoxyglucose-positron emission tomography/computed tomography could be applied to a murine model of advanced atherosclerotic plaque vulnerability to detect response to therapeutic intervention and changes in lesion stability. Approach and Results: To analyze plaques susceptible to rupture, we fed ApoE mice a high-fat diet and induced vulnerable lesions by cast placement over the carotid artery. After 9 weeks of treatment with orthogonal therapeutic agents (including lipid-lowering and proefferocytic therapies), we assessed vascular inflammation and several features of plaque vulnerability by F-fluorodeoxyglucose-positron emission tomography/computed tomography and histopathology, respectively. We observed that F-fluorodeoxyglucose-positron emission tomography/computed tomography had the capacity to resolve histopathologically proven changes in plaque stability after treatment. Moreover, mean target-to-background ratios correlated with multiple characteristics of lesion instability, including the corrected vulnerability index.
These results suggest that the application of noninvasive F-fluorodeoxyglucose-positron emission tomography/computed tomography to a murine model can allow for the identification of vulnerable atherosclerotic plaques and their response to therapeutic intervention. This approach may prove useful as a drug discovery and prioritization method.
本研究旨在探讨 F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(F-fluorodeoxyglucose-positron emission tomography/computed tomography,FDG-PET/CT)能否应用于检测治疗干预反应和病变稳定性变化的晚期动脉粥样硬化斑块易损性的小鼠模型中。
为了分析易破裂斑块,我们用高脂肪饮食喂养载脂蛋白 E(ApoE)小鼠,并通过颈动脉放置套管来诱导易损性病变。在使用正交治疗药物(包括降脂和促进吞噬治疗)治疗 9 周后,我们分别通过 FDG-PET/CT 和组织病理学评估血管炎症和斑块易损性的几个特征。我们观察到 FDG-PET/CT 能够在治疗后分辨出组织病理学上证实的斑块稳定性变化。此外,平均靶标与背景比与病变不稳定的多个特征相关,包括校正的易损性指数。
这些结果表明,将非侵入性 FDG-PET/CT 应用于小鼠模型可以识别易损性动脉粥样硬化斑块及其对治疗干预的反应。这种方法可能有助于作为一种药物发现和优先级确定方法。