Molecular imaging for noninvasive evaluation of atherosclerotic plaque vulnerability

易损动脉粥样硬化斑块的破裂和随后的血栓形成是缺血性疾病如脑梗死和心肌梗死的主要原因。因此，临床上需要检测易损动脉粥样硬化斑块，以便早期选择和给予适当的治疗。分子影像学技术能够检测正常和生物病理过程中涉及的细胞分子事件，并为基于生物学特征的易损斑块的鉴别提供了很大的优势。同时，据报道，巨噬细胞广泛地促进斑块中炎症的发展，并使用葡萄糖作为能量产生的必要底物。此外，氧化LDL的细胞表面受体凝集素样氧化LDL受体-1（LOX-1）与动脉粥样硬化斑块不稳定性相关的血管细胞功能障碍有关。在这项研究中，我们调查了在不同的年龄段， ...更多信息 18-F-FDG，一种葡萄糖衍生物和斑块不稳定性之间的关系，以及LOX-1表达和斑块不稳定性之间的关系，使用高胆固醇血症兔。这些研究表明，18-F-FDG蓄积和LOX-1表达与免疫组化检测的动脉粥样硬化不稳定性密切相关。基于双功能螯合物的概念，设计了99 m-Tc标记的抗LOX-1抗体，并研究了其在动脉粥样硬化病变中的蓄积。因此，99 m-Tc-抗LOX-1抗体的积累与动脉粥样硬化不稳定性密切相关。结果表明，18-F-FDG和99 m-Tc-抗LOX-1抗体可用于选择性检测动脉粥样硬化易损斑块。此外，我们开发了一种带电粒子敏感探测器，用于血管内小斑块的检测，因为血池的高背景放射性，空间分辨率差和复杂的身体运动使得难以通过外部成像检测小斑块，特别是冠状动脉斑块。该装置中的探头由塑料闪烁体和外径仅为1.0 mm的柔性光纤组成。该探测器可以探测附着在体模、犬股动脉和冠状动脉上的点源，具有良好的分辨率、灵敏度和重复性。因此，新的探针和仪器的发展将使分子成像在斑块易损性的临床诊断中成为更有用的方法。少

The rupture of vulnerable atherosclerotic plaques and subsequent thrombus formation are the major cause of ischemic diseases, such as cerebral and myocardial infarction. Thus, the detection of vulnerable atherosclerotic plaques has been clinically desirable for early selection and administration of appropriate therapy. Molecular imaging techniques are able to detect cellular molecular events involved in normal and biopathologic processes and offer a great advantage for the discrimination of vulnerable plaques on basis of biologic characteristics. Meanwhile, it has been reported that macrophages contribute extensively to the development of inflammation in plaques and use glucose as an essential substrate for energy production. Furthermore, lectine-like oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL, has been implicated in vascular cell dysfunction related to atherosclerotic plaque instability. In this study, we investigated the relationship between the accumul … More ation of 18-F-FDG, a glucose derivative and plaque instability and between LOX-1 expression and plaque instability, using hypercholesterolemic rabbits. These studies demonstrated that 18-F-FDG accumulation and LOX-1 expression were strongly correlated with atherosclerotic instability detected by immunohistochemical study. Furthermore, anti-LOX-1 antibody labeled with 99m-Tc was designed based on the concept of bifunctional chelate and its accumulation in atherosclerotic lesions was investigated. Consequently, the accumulation of 99m-Tc-anti-LOX-1 antibody was strongly correlated with atherosclerotic instability. These results indicate that 18-F-FDG and 99m-Tc-anti-LOX-1 antibody are useful for the selective detection of vulnerable atherosclerotic plaques. Furthermore, we developed a charged particle-sensitive detector for the endovascular detection of small plaques because high background radioactivity from the blood pool, poor spatial resolution and complex body motion make it difficult to detect small plaques by external imaging, especially in the coronary plaques. The probe in this device consists of a plastic scintillator and flexible optical fibre, which is only 1.0 mm in outer diameter. This detector could detect the point sources attached to a phantom, canine femoral artery and coronary artery, with good resolution, sensitivity and repeatability. Thus, the development of new probes and instruments would make molecular imaging a more useful method in the clinical diagnosis of plaque vulnerability. Less