Development of positron labeled polyunsaturated long chain fatty acid to image the brain phospholipid metabolism with positron emission tomography.

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We have completed the following matters in these two year term under the Grant-in-Aid for Developmental Scientific Research.1, Precursor in the course of the radio synthesis of ^<11>C labeled docosahexaenoate (^<11>C-DHA), all-z-1-bromo-3, 6, 9, 12, 15, 18-heneicosahexaene, were successfully synthesized from commercially available ethyl docosahexaenoate. 2, The ^<11>C-DHA was synthesized with two step procedure through the reaction of bromo substances with metal lithium and the trapping of ^<11>CO_2 in the reaction vessel. 3, The organ distribution of radioactivity after 20 min. bolus injection of ^<11>C-DHA were examined. Although the uptake of brain was less than 1% dose/g tissue, brain images using autoradiography were successfully obtained. 4, The distribution of radioactivity in the brain lipid fraction were examined by extracting brain lipid and with autoradiographic TLC analysis. It revealed that the radioactivity mainly exist in the brain phospholipid fraction, especially in th … More e phosphatidylethanolamine fraction. 5, The uptake of ^<11>C-DHA with and without systemic treatment with cholinergic agonist arecoline were examined. The uptake ratio of ^<11>C-DHA into cerebral cortex, which is rich in the muscarinic cholinergic receptor, showed increase by cholinergic treatment. However, that into cerebellum, which lacks muscarinic cholinergic receptor did not. 6, The uptake of ^<11>C-DHA into periinfarct area of rat's unilateral MCA occlusion model showed increase 1 hour after occlusion, which may indicate the increased release of sn-2 position fatty acids coupled with the activation of phospholipase A2.7, The experiment to examine the alteration of the turnover of sn-2 position fatty acids using brain trauma model of rats were started.The things which are remained to be completed are as follows. 1, In order to obtain the commercially distributed bromoprecursor substances for the continuous clinical usage of ^<11>C-DHA, we asked several pharmaceutical companies. However, the agreement could not be obtained from any companies by now. 2, Brain imaging experiment using larger animal such as monkey to proceed this imaging method into human study could not be performed in these two year period because of several limitation in experimental facilities. These two will continuously tried in next year. Less