Treatment of intractable epilepsy by stereotactic intracerebral injection of alpha-emitting nuclide At-211

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Osaka University
• Principal Investigator: Kato Hiroki 大阪大学, 医学系研究科, 准教授 (20448054)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: RI治療 / てんかん / α線 / アスタチン

Outline of Final Research Achievements

When we administered the compound (50 kBq / μL) labeled with 211At into bilateral hippocampus of rats, the compound stayed at the injection site for a long time and did not spread systemically. According to 18F-FDG PET of the rat brain after administration, no obvious abnormalities in cerebral metabolism was observed. Furthermore, the Y-maze test confirmed no obvious abnormality in the working memory. Immunohistological examination of brain tissue revealed no obvious abnormalities in nerve cells and glial cells. It was found that when the compound was modified to suppress aggregation and the concentration (radioactivity) was further increased by about 10 times, it still remained locally without systemic spread. When the drug was administered to pentylenetetrazole (PTZ) kindling model rats, a significant seizure-suppressing effect was observed. The Y-maze test showed no apparent effect on working memory or activity.

Free Research Field

核医学

Academic Significance and Societal Importance of the Research Achievements

薬剤治療抵抗性の難治性てんかんでは、発作焦点が同定できれば手術による切除が施行されるが、侵襲性が高い。ガンマナイフによる外照射にて発作焦点を破壊する治療もおこなわれているが、副作用が強く忍容性が低い。集束超音波治療やラジオ波焼灼術なども提案されているが効果は定まっていない。中枢神経は放射線による影響が少ないと考えられている。申請者らはα線放出核種の定位的脳内注入による全く新しい難治性てんかんの低侵襲治療法を提案し、それを検証した。