Joint Study on Brain Imagimg with Radiolabeled Fatty Acids

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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.