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

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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.