抄録
There exist 1 million epileptic patients in Japan and approximately 25% of them suffer from drug-resitant intractable epilepsy. Although surgery to remove epileptic focus is effective for intractable epilepsy, only 7% of cases with intractable epilepsy are surgical indication. One major reason for this low number of surgical indication is due to the technical limitation in current non-invasive tools to indetify epileptic focus such as FDG-PET, MRI and scalp EEG. Thus, a development of novel more sensitive imaging technology to identify focus is a unmet medical needs.
Glutamate AMPA (alfa-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor (AMPAR) plays central roles in neuronal functions and epileptogenesis. However, clinical translation of knowledge on AMPAR accumulated in a number of animal studies is limited due to the inability to visualize AMPARs in living human brain. Thus, we developed positron emission tomography (PET) tracer for AMPARs. We radio-labelled carbon of newly synthesized complound named K-2 originally binding to AMPARs specifically and this PET tracer detected specific AMPARs PET signals in rat. After completing the studies to examine toxicity of K-2, we performed first-in-human trial with healthy individuals and they exhibited characteristic AMPAR PET signals. Next, we imaged patients with temporal lobe epilepsy and found prominent accumulation of specific signals in mesial temporal lobe of focus side where FDG PET signal was prominently low. These data strongly suggested that our PET tracer is a promising tool to identify epileptic focus with superior sensitivity than current non-invasing technology. In this study we also examine the correlation of PET signals and AMPAR protein amount in surgically resected tissues from epileptic patients for further validation of our AMPAR PET probe. We expect this study will further elucidate the mechanisims of epileptogenesis and dramatically increase the number of epileptic patients who can take surgery by the identification of epileptic focus leading to the better quality of life by the remission of epilepsy.
