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血栓形成是缺血性透明的心脏梗塞的主要原因。和生物病理学的过程为生物学特征的歧视提供了巨大的优势。细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞细胞和细胞细胞细胞细胞L S研究了累积之间的含量……葡萄糖衍生物和斑块不稳定性以及LOX-1和斑块的稳固性，使用高胆固醇血症兔子。 -1与99m-tc的表达强烈相关。 99M-TC-LOX-1 ODY是对脆弱的动脉粥样硬化斑块的选择性检测，我们开发了一个带电的粒子 - 粒子检测器，用于对小斑块的血管内检测。柔性纤维在外部检测到的点源点仅1.0毫米，并具有良好的分辨率，灵敏度和重复性，因此，新的探针和仪器的发展将分子的发展。成像一种更有用的方法在斑块脆弱性的临床诊断中

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