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

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 Ii D13e D1H and I D111 D1C.2..Using I D13 I D 1H-L-NAME，we demonstrated that uptake of L-NAME by endothelial cells can reflect the activity of NO production(NOS Activity)体外.3.Using I D111 I D 1C-L-NAME，we succeeded in vitro PET imaging of endothelial cells.4.Ionomycin，the calcium ionohore augmented the uptake of I D 111 ii D 1C-L-NAME and we could detect more intense imaging of endothelial cells treated with ionomycin compared with the control.These results sugest that PET imaging using labeled L-ME NAcan 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。

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.