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

• 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

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和随后的血栓形成的破裂是缺血性疾病的主要原因，例如大脑和心肌梗塞。这是临床期望在临床上进行早期选择和适当治疗的检测。分子成像技术能够检测到正常和生物病理学过程中涉及的细胞分子事件，并根据生物学特征歧视脆弱的斑块。同时，据报道，巨噬细胞有助于斑块中感染的发展，并使用葡萄糖作为能量生产的必不可少的底物。此外，在与动脉粥样硬化斑块不稳定性有关的血管细胞功能障碍中隐含了氧化LDL的氧化LDL受体1（LOX-1），一种用于氧化LDL的细胞表面受体。在这项研究中，我们使用高胆固醇血症兔子研究了累积……更多的18-F-FDG，葡萄糖衍生物和斑块不稳定性以及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表达与通过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，研究了基于双功能樱桃的概念设计的抗LOX-1抗体，研究了其在动脉粥样硬化病变中的积累。因此，99m-TC-ANTI-LOX-1抗体的积累与动脉粥样硬化的不稳定性密切相关。这些结果表明，18-F-FDG和99M-TC-ANTI-LOX-1抗体可用于选择性检测脆弱的动脉粥样硬化斑块。此外，我们开发了一种带电的粒子敏感探测器，用于对小斑块进行血管内检测，因为血液库的高背景放射性，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，尤其是在冠状斑块中。该设备中的探针由塑料闪烁体和柔性光纤组成，外径仅为1.0 mm。该检测器可以检测到幻影，犬股动脉和冠状动脉附加的点源，具有良好的分辨率，灵敏度和可重复性。这，新问题和工具的发展将使分子成像成为斑块脆弱性临床诊断的更有用的方法。较少的

项目成果

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

应用[^ 18 F]FDG-PET监测抗炎药物对稳定易损动脉粥样硬化斑块的治疗效果。

• 发表时间: 2006
• 期刊: J.Nucl.Med. 48(11)
• 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.

Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with

凝集素样氧化 LDL 受体-1 (LOX-1) 表达与

• 发表时间: 2007
• 期刊: Atherosclerosis. (印刷中)
• 作者: Ishino S;Kuge Y;Takai N;Tamaki N;Strauss HW;Blankenberg FG;Shiomi M;Saji H.;Yuji Kuge;Hideo Saji
• 通讯作者: Hideo Saji

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。

• 发表时间: 2006
• 期刊: J.Nucl.Med. 48・11
• 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

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。

• 发表时间: 2006
• 期刊: J. Nucl. Med. 47・5
• 作者: R.Hosokawa;N.Kambara;M.Ohba;T.Mukai;M.Ogawa;H.Motomura;N.Kume;H.Saji;T.Kita;R.Nohara
• 通讯作者: R.Nohara

(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

• 发表时间: 2007
• 期刊: Eur J Nucl Med Mol Imaging 34(印刷中)
• 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