Development of highly-sensitive evaluation method of endothelial cell function and early diagnostic procedure of atherosclerosis by positron emission tomography

早期发现与高血压、糖尿病合并的动脉粥样硬化或高血脂在临床上是非常严重的。动脉粥样硬化的诊断程序有很多问题;例如，它们是非常敏感的，只能检测到高级的问题，或者它们是非常侵入性的，而且需要很高的技术。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.我们获得了以下结果：1. We succeeded in the labeling of L-NAME， the NOS inhibitor byイD13イエD1H andイD111イエD1C.2。使用D13 D1 H-L-NAME，我们演示用内皮细胞提升L-NAME可以反映体外无生产（NOS活动）的活动。使用D111 D1C-L-NAME，我们成功地在体外PET成像的内分泌细胞。离子霉素，钙离子ohore增强的uptake of D111离子D1C-L-NAME，我们可以检测到更多的内皮细胞成像与离子霉素比较。这些结果建议使用标签L-NAME进行PET成像可以是内皮功能（NO production）的评估方法。迈向我们方法的体内应用，寻找更稳定的L-NAME相关化合物及其PET成像所需的标签。

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.