Non-invasive measurement of cerebral inhibitory receptors and their neural circuit in epileptgenic

1)所有在东京医科齿科大学神经外科手术的难治性癫痫患者均进行了脑葡萄糖代谢率和中枢苯二氮卓类受体结合电位的PET测量。2001年，开始了一个新的项目，用C-11多虑平和PET对癫痫灶中的脑组胺受体进行成像。2）我们正在开发一种新的受体配体，用于脑腺苷受体系统的定位。通过该项目，C-11 MPDX被认为是PET体内条件下成像A1受体的合适配体。用猫和猴进行了确定该示踪剂有效性的临床前研究，并积累了足够的数据表明该示踪剂的有效性和安全性。根据这些数据，将在下一个财政年度开始进行人脑腺苷A1受体的PET成像。3）如上所述，可以使用PET测量人脑中的苯二氮卓类和腺苷受体系统。为证实这两种受体系统在致痫中的作用，采用大鼠边缘系统癫痫模型进行了体外放射自显影实验。4）建立了用正电子示踪法研究癫痫大鼠脑组织代谢和受体结合的方法。一个新的项目开始将这项技术应用于从癫痫患者身上获得的人脑标本。

1) All the patients with intractable epilepsy who were operated on in Department of Neurosurgery, Tokyo Medical and Dental University underwent PET measurement of cerebral metabolic rate of glucose and the binding potential, of central benzodiazepine receptors. In 2001, a new project to image cerebral histamine receptor in epileptic foci with C-11 doxepine and PET was started. The results are ready to be analized with kinetic analysis of receptor binding.2) We have been developing a novel receptor ligand to map cerebral adenosine receptor system. Through this project, C-11 MPDX was recognized as a suitable ligand to image A1 receptor in vivo condition with PET. Pre-clinical research to establish the efficacy of this tracer was conducted with cat and monkey and enough data to indicate the usefulness and safetiness of this tracer was accumulated. Based on this data, PET imaging of adenosine A1 receptor in human brain will be started in next fiscal year.3) As described above, measurement of benzodiazepine and adenosine receptor system in human brain is and will be possible with PET. To confirm the contribution of these two receptor system in epileptogenicity, in vitro autoradiographical experiment was conducted with rats model of limbic seizure. Increased expressinon of these receptors was recognized in hippocampus of epilepsy rats.4) A method to investigate the cerebral metabolism and receptor binding using incubated living brain slice was developed using positron tracer. A new project to apply this technique to human brain specimen obtained from epilepsy patients was started.