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Joint Study on Brain Imagimg with Radiolabeled Fatty Acids

放射性标记脂肪酸脑成像联合研究

基本信息

批准号：
05044152
负责人：
HIRAKAWA Kimiyoshi
金额：
$ 3.2万
依托单位：
Tokyo Medical & Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

The aim of our joint project is to develop several positron labeled fatty acid applicable for human brain imaging with positron emission tomography (PET). We have already synthesized C11 labeled palmitate, arachidonate and docosahexaenoate and have been evaluating their incorporation into normal or pathologic brain using large or small animals. Besides the investigator and co-investigators included in this grant, two NIH visiting fellow from Tokyo Medical and Dental University (Drs.Wakabayashi and Arai) were involved in this project.The following results were obtained. 1) Monkey PET study using C11 labeled fatty acids revealed that the structure and function of brain can be imaged with PET.2) It also was found that C11 labeled saturated palmitate is highly oxidized after intravenous injection. Therefore, an inhibitor of ァーoxidation (methyl palmoxirate) should be applied with to image brain lipid metabolism. 3) Although we have submitted human PET protocol, in which normal volunteers and patients with glioma, Alzheimer disease and Nieman-Pick disease type C will be examined with PET,we could not start human study in this study period because the FDA approval of methyl palmoxirate, which will be expected soon, have not been obtained in study period. 4) In vivo autoradiographic research using rats were conducted in several disease model with reference to glucose metabolism and blood flow study. The study with rats' enucleation model and kindling model have been completed successfully. The pathological changes which could not be detected by glucose metabolism were detected with fatty acid autoradiogram. The study with rats' brain injury model and acute brain ischemia have been started. Preliminary results suggest that the hyper activation of phospholipase A2 can be imaged with radiolabeled unsaturated fatty acid.Summarizing these results, application of this method in human brain disease will be started in coming year.

我们的合作项目的目的是开发几个正电子标记的脂肪酸适用于人脑成像与正电子发射断层扫描（PET）。我们已经合成了C11标记的棕榈酸酯、花生四烯酸酯和二十二碳六烯酸酯，并使用大型或小型动物评估了它们与正常或病理脑的结合。除了研究者和合作研究者外，东京医科齿科大学的两名NIH访问学者（若林博士和新井博士）也参与了本项目。1)使用C11标记的脂肪酸的猴PET研究揭示了脑的结构和功能可以用PET成像。2）还发现C11标记的饱和棕榈酸酯在静脉注射后高度氧化。因此，应使用抗氧化剂（棕榈酸甲酯）对脑脂质代谢进行成像。3)虽然我们已经提交了人体PET方案，其中将对正常志愿者和神经胶质瘤、阿尔茨海默病和C型尼曼-匹克病患者进行PET检查，但我们无法在本研究期间开始人体研究，因为在本研究期间尚未获得FDA对棕榈酸甲酯的批准（预计很快会获得批准）。4)利用大鼠在几种疾病模型中进行了体内放射自显影研究，并参考了葡萄糖代谢和血流研究。成功地完成了大鼠眼球摘除模型和点燃模型的研究。脂肪酸放射自显影检测糖代谢不能检测的病变。本研究采用大鼠脑损伤模型和急性脑缺血模型进行研究。初步结果表明，放射性标记的不饱和脂肪酸可用于磷脂酶A2的超活化成像，并将在明年开始应用于人类脑疾病的研究。