Joint Study on Brain Imagimg with Radiolabeled Fatty Acids

我们的联合项目的目标是用于人类大脑成像的目标（PET）。我们已经合成了C11标签的棕榈酸盐、花生酸盐和十二烷酸盐，并且已经用大型或小型动物来评估它们的增加正常或病理学大脑。Besides的调查员和联合调查员包括在本赠款中，两名来自东京医学和牙科大学的NIH访问者（Wakabayashi博士和Arai博士）参与了这个项目。后续结果获得了。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 found that that C11 labeled saturated palmitate is highly oxidized after intravenous injection。因此，一种氧化物（甲基硫酸钠）的抑制剂应该被应用于图像大脑脂质代谢。3）我们已经提交了人类PET协议，在患有胶质瘤、阿尔茨海默病和尼曼-皮克病的C型正常病例和患者中，我们将对PET进行测试，我们不能开始在这个研究期间进行人类研究，因为FDA批准了甲基丙二酯，我们将很快被期望，在研究期间没有被发现。4）在体内使用大鼠在多种疾病模型中的行为进行自动医学研究，并参考葡萄糖代谢和血液流动研究。用老鼠的核模型和点燃模型进行的研究已经成功地完成了。这种病理学变化是用脂肪酸自动流变学检测不到的，而葡萄糖元化是用脂肪酸自动流变学检测到的。用老鼠脑损伤模型进行的研究和急性脑损伤已经开始了。初步结果表明，磷脂酶A2的超激活可以用放射性不饱和的脂肪酸来成像。总结这些结果，这种方法在人类大脑疾病中的应用将在明年开始。

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.