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

开发正电子标记的多不饱和长链脂肪酸，通过正电子发射断层扫描对脑磷脂代谢进行成像。

• 批准号: 04557062
• 负责人: HIRAKAWA Kimiyoshi
• 金额: $ 10.5万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557062/
• 关键词: PHOSPHOLIPIDS; FATTY ACIDS; DOCOSAHEXAENOIC ACID; ARACHIDONIC ACIDS; PET; BRAIN METABOLISM; CYCLOTRON; PHOSPHOLIPASE; ポジトロン標識化合物; オートラジオグラフィー

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

在发展性科学研究资助计划下，我们在这两年的时间里完成了以下工作：1、以市售的二十二碳六烯酸乙酯为原料，成功地合成了放射性合成^<11>C标记二十二碳六烯酸（^<11>C-DHA）的前体--全直-1-溴-3，6，9，12，15，18-二十一碳六烯。2、<11>以溴代物和金属锂为原料，采用捕集反应器捕集二氧化碳的方法，通过两步反应合成了α-C-DHA<11>。3、观察大鼠静脉注射α-C-DHA 20分钟后放射性的器官分布<11>。尽管脑摄取低于1%剂量/g组织，但成功获得了使用放射自显影术的脑图像。4、通过提取脑脂质并进行放射自显影TLC分析，检测脑脂质组分中放射性的分布。表明放射性主要存在于脑磷脂部分，尤其是脑组织中 ...更多信息 e磷脂酰乙醇胺级分。5.<11>用胆碱能激动剂槟榔碱全身治疗和不全身治疗，检测了对β-C-DHA的摄取。胆碱<11>能处理可增加富含毒蕈碱胆碱能受体的大脑皮层对1C-DHA的摄取率。然而，进入小脑，其中缺乏毒蕈碱胆碱能受体没有。6、<11>大鼠一侧MCA闭塞模型梗死周围区对1C-DHA的摄取在闭塞后1小时增加，这可能表明sn-2位脂肪酸的释放增加与磷脂酶A2的激活有关。7、利用大鼠脑外伤模型研究sn-2位脂肪酸的转换变化，尚待完成的工作如下。1、为了获得商业上销售的溴前体物质用于连续临床使用^<11>C-DHA，我们询问了几家制药公司。然而，到目前为止，该协议无法从任何公司获得。2、由于实验设备的限制，在这两年时间里，无法利用猴等大型动物进行脑成像实验，将这种成像方法应用于人体研究。这两个案件将在明年继续审理。少

项目成果

Robinson PJ et al.: "A quantitative method for measurering regional in vivo fatty-acid incorporation into and turnover within brain phospholipids : review and critical comments." Brain Res Rev. vol.17. 187-214 (1992)

Robinson PJ 等人：“一种测量体内区域脂肪酸掺入脑磷脂和脑磷脂内周转的定量方法：评论和批评意见。”

Nobuhisa Nagano et al.: "Invasion of experimental rat brain tumor : early morphological changes following microinjection of C6 glioma cells." Acta Neuropathol. vol.86. 117-125 (1993)

Nobuhisa Nagano 等人：“实验性大鼠脑肿瘤的侵袭：显微注射 C6 神经胶质瘤细胞后的早期形态变化。”

Tsutomu Asano et al.: "Effect of endothelin-1 as growth factor on a human glioma cell line;its characteristic promotion of DNA synthesis." J Neurooncol. 17 (in press). (1994)

Tsutomu Asano 等人：“内皮素 1 作为生长因子对人神经胶质瘤细胞系的影响；其特有的促进 DNA 合成的作用。”

Robinson PJ et al.: "A quantitative method for measurering regional in vivo fatty-acid incorporation into and turnover within brain phospholipids:review and critical comments." Brain Res Rev. 17. 187-214 (1992)

Robinson PJ 等人：“一种测量体内区域脂肪酸掺入脑磷脂和脑磷脂周转的定量方法：评论和批评评论。”

Tadashi Nariai et al.: "Surgically induced angiogenesis to compensate for hemodynamic cerebral ischemia" Stroke. 25(in press). (1994)

Tadashi Nariai 等人：“手术诱导血管生成以补偿血流动力学脑缺血”中风。