| Project/Area Number |
10557050
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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 | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ITOH Hiroshi Kyoto University, Graduate School of Medicine, Department of Medicine and Clinical Science, Assistant Professor, 医学研究科, 助手 (40252457)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKADA Hideo Hamamatsu Photonics Co., Central Laboratory, Chief Researcher, 中央研究所, 専任部員
NISHIMURA Shintaro Fujisawa Pharmaceutical Industry Co., Basic Technique Laboratory, Chief Researcher, 基盤技術研究室, 主任研究員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Endothelial Cells / Nitric Oxide (NO) / NO synthase (NOS) / Positron Emission Tomography (PET) / Atherosclerosis / Calcium Ionophore / TGF-β / 一酸化窒素 / カルシウム |
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| Research Abstract |
Early detection of atherosclerosis complicated with hypertension, diabetes mellitus or hyperlipidemia is clinically very crucial. Diagnostic procedure of atherosclerosis so far have many problems; for example, they are very insensitive and detect only advanced lesions or they are very invasive and require high technique. This research project aims at establishment of a new diagnostic method of atherosclerosis to evaluate the decreased activity of nitric oxide (NO) synthase (NOS) in endothelial cells by utilizing PET.
We obtained the following results:
1. We succeeded in the labeling of L-NAME, the NOS inhibitor by ィイD13ィエD1H and ィイD111ィエD1C.
2. Using ィイD13ィエD1H-L-NAME, we demonstrated that uptake of L-NAME by endothelial cells can reflect the activity of NO production (NOS activity) in vitro.
3. Using ィイD111ィエD1C-L-NAME, we succeeded in in vitro PET imaging of endothelial cells.
4. Ionomycin, the calcium ionohore augmented the uptake of ィイD111ィエD1C-L-NAME and we could detect more intense imaging of endothelial cells treated with ionomycin compared with the control.
These results suggest that PET imaging using labeled L-NAME can be the evaluation method of endothelial function (NO production). Towards the in vivo application of our method, search for metabolically more stable L-NAME-related compounds and their labeling for PET imaging are required.
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