| Project/Area Number |
16390337
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
SAJI Hideo Kyoto University, Graduate of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (40115853)
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| Co-Investigator(Kenkyū-buntansha) |
KUGE Yuji Kyoto University, Graduate School of Pharm.Sci., Associate Professor, 薬学研究科, 助教授 (70321958)
TADAMURA Eiji Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70303831)
KUME Noriaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20252455)
NOHARA Ryuji Kitano Hospital, Division of Cardiology, Research Director, 医学研究所・第3研究部, 研究主幹 (80180769)
MUKAI Takahiro Kyushu University, Faculty of Pharm.Sci., Associate Professor, 薬学研究院, 助教授 (30284706)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | 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 |
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| Research Abstract |
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
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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
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