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Molecular imaging for noninvasive evaluation of atherosclerotic plaque vulnerability

用于无创评估动脉粥样硬化斑块脆弱性的分子成像

基本信息

批准号：
16390337
负责人：
SAJI Hideo
金额：
$ 9.15万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390337/
关键词：
thrombosis vulnerable plaque molecular imaging radiation detector glucose derivative lectine-like oxidized LDL receptor macrophage radiolabeled molecular probe 超小型放射線検出器 LOX-1 F-18

项目摘要

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

脆弱的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（例如脑梗塞和心肌梗塞）的主要原因。因此，临床上需要检测易损动脉粥样硬化斑块，以早期选择和给予适当的治疗。分子成像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，并为根据生物学特征区分易损斑块提供了巨大的优势。同时，据报道，巨噬细胞广泛促进斑块炎症的发展，并利用葡萄糖作为能量产生的重要底物。此外，凝集素样氧化 LDL 受体-1 (LOX-1)（一种氧化 LDL 的细胞表面受体）与动脉粥样硬化斑块不稳定相关的血管细胞功能障碍有关。在这项研究中，我们使用高胆固醇血症兔子研究了 18-F-FDG（一种葡萄糖衍生物）的积累与斑块不稳定性之间的关系以及 LOX-1 表达与斑块不稳定性之间的关系。这些研究表明，18-F-FDG 积累和 LOX-1 表达与免疫组织化学研究检测到的动脉粥样硬化不稳定性密切相关。此外，基于双功能螯合物的概念设计了99m-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积累。因此，99m-Tc-抗LOX-1抗体的积累与动脉粥样硬化不稳定性密切相关。这些结果表明 18-F-FDG 和 99m-Tc-抗 LOX-1 抗体可用于选择性检测易损动脉粥样硬化斑块。此外，我们开发了一种带电粒子敏感探测器，用于血管内检测小斑块，因为血池的高背景放射性、较差的空间分辨率和复杂的身体运动使得通过外部成像很难检测小斑块，特别是冠状动脉斑块。该装置中的探头由塑料闪烁体和柔性光纤组成，外径仅为1.0毫米。该探测器可以检测附在体模、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，新探针和仪器的开发将使分子成像成为斑块易损性临床诊断中更有用的方法。较少的

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Application of [^<18>F]FDG・PET for monitoring the therapeutic effect of anti inflammatory drugs on stabilization of vulnerable atherosclerotic plaques.

[^18F]FDG·PET在监测抗炎药物稳定易损动脉粥样硬化斑块的治疗效果中的应用。

DOI：
发表时间：
2006
期刊：
J.Nucl.Med. 48・11
影响因子：
0
作者：
M.Ogawa;Y.Magata;T.Kato;K.Hatano;S.Ishino;T.Mukai;M.Shiomi;K.Ito;H.Saji
通讯作者：
H.Saji

(99m)Tc-Annexin A5 for noninvasive characterization of atherosclerotic lesions : imaging and histological studies

(99m)Tc-Annexin A5 用于动脉粥样硬化病变的无创表征：成像和组织学研究

DOI：
发表时间：
2007
期刊：
Eur J Nucl Med Mol Imaging 34(印刷中)
影响因子：
0
作者：
Ishino S;Kuge Y;Takai N;Tamaki N;Strauss HW;Blankenberg FG;Shiomi M;Saji H.;Yuji Kuge;Hideo Saji;Hideo Saji
通讯作者：
Hideo Saji

A catherer-based intravascular radiation detector for vulnerable plaques.

基于导管的血管内辐射探测器，用于检测易损斑块。