Development of next generation BNCT targeted to the tumor endothelial cell

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Hatakeyama Shingo 弘前大学, 医学研究科, 准教授 (10400136)
• Co-Investigator(Kenkyū-buntansha): 米山 徹 弘前大学, 医学研究科, 助教 (50587649) ; 大山 力 弘前大学, 医学研究科, 教授 (80282135)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 中性子補足療法 / 癌特異的療法

Outline of Final Research Achievements

To improve the current anticancer drug treatment issues, we investigated the efficacy of next-generation neutron supplementation therapy using the IF7 peptide and boron or gadolinium.
The compound IF7-BSH, which combines IF7 and boron, was found to exhibit antitumor effects at doses as low as 1/25 of those of conventional BPA agents. A gadolinium cross-linked 157Gd-IF7 compound was subsequently prepared, and its accumulation was confirmed by animal MRI, but urinary excretion was enhanced and it was excreted in the urine before collecting in the tumor. Tumor accumulation by administration of the 157Gd-IF7 compound was also not confirmed.
For clinical application, the development of IF7-BSH-based therapies may be useful.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

中性子捕捉療法は腫瘍特異的な細胞傷害作用を示す放射線治療法である。有望な次世代放射線治療として注目されているが、10BやGd薬剤の腫瘍細胞への集積効率が悪く、将来的な治療適応拡大のためには、腫瘍特異性を改選する必要があった。我々は、腫瘍血管内皮表面に発現するアネキシンA1に結合するIF7ペプチドとホウ素製剤の複合薬剤(IF7-BSH/BPA)を開発し、既存ホウ素製剤に比べ、600倍の腫瘍特異的ホウ素集積を示し、抗腫瘍効果を明らかにした。臨床応用までにはまだ時間が必要であるが、現在の抗がん剤治療の課題を改善する試みとして研究成果の学術的意義や社会的意義は大きいと考えられる。