Tumor targeting using boron neutron capture therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• 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) ; 石山 新太郎 弘前大学, 理工学研究科, 教授 (60355021) ; 飛澤 悠葵 弘前大学, 医学研究科, 助教 (70623768) ; 大山 力 弘前大学, 医学研究科, 教授 (80282135)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 中性子補足療法 / 糖鎖生物学 / がん化学療法 / 手術療法

Outline of Final Research Achievements

We developed a tumor-targeting Boron neutron capture therapy (BNCT) using tumor vasculature endothelium targeting peptide (IF7) conjugated boronophenylalanine (BPA-IF7) to improve the biodistribution of BPA. BPA or BPA-IF7 (7 mg/kg, 1/35 of effective dose) was intravenously administrated to MBT2 tumor-bearing mice. The tumors received reactor thermal neutron beam irradiation following the administration of 7 mg/kg of BPA-IF7. Tumor growth was compared between the irradiated (n=7) and control (n=19) mice for 2 weeks.Tumor concentration of B10 was 5-fold higher in the BPA-IF7 than that in the BPA. The tumor concentration of B10 reached 20 ppm within the 20 min in the BPA-IF7 mice. Tumor size was significantly decreased in the BPA-IF7 mice than that in the control mice. BPA-IF7 showed faster tumor-specific boron accumulation than conventional BPA and showed antitumor effects at low doses. BPA-IF7 has the potential to improve drug delivery of BPA and antitumor effect for BNCT.

Free Research Field

泌尿器がん

Academic Significance and Societal Importance of the Research Achievements

現在の抗がん剤治療が抱える弱点は、細胞毒性の強い薬剤を全身投与する点にある。これら副作用を減らし高い抗腫瘍効果を得るためには高濃度の抗がん剤をがんのみに到達させる必要がある。我々の開発したB-IF7は、がん細胞に高濃度にホウ素を集積させることが出来るため、これら問題を解決できる可能性がある。さらに最近になって頭頚部癌に対する中性子補足療法が保険適応となったことを受け、中性子発生装置も広く普及していくものと思われ、我々の研究成果は学術的意義ならびに社会的意義の高い結果と思われる。