Study on cerebrospinal fluid administration of boron agent for brain tumor for BNCT

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16412
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Osaka University
• Principal Investigator: KUSAKA Sachie 大阪大学, 大学院工学研究科, 技術職員 (30781314)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ホウ素中性子捕捉(BNCT) / 脳脊髄液 / ホウ素薬剤 / 脳腫瘍 / Drug delivery system / 質量分析イメージング

Outline of Final Research Achievements

This study proposed "boron delivery using cerebrospinal fluid circulation" as a novel boron drug delivery method for brain tumor patients to be treated with boron neutron capture therapy. The delivery method was compared with the intravenous (IV) injection. Both methods achieved similar boron concentrations in the brain of rats, even though the doses of boron drug, boronophenylalanine (BPA), involved in the cerebrospinal fluid-based method are lower, less than 1/10 those involved in the IV method. In addition, we have established a matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging protocol to acquire BPA distribution images in the rat brain and have succeeded in developing a technique for measuring an image of approximately 1 cm square and 60 μm spatial resolution (60 μm pixel size). The image demonstrated the brain tumor selectivity of BPA administered via cerebrospinal fluid.

Free Research Field

放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

ホウ素中性子捕捉療法では、ホウ素の腫瘍細胞での高濃度蓄積と腫瘍細胞選択性が求めらる。ホウ素脳脊髄液投与法は、血管投与法と比べ、投与量がはるかに少ないにも関わらず、脳内のホウ素濃度を高めたことは、この投与法により薬物の毒性のリスクとコストを抑えることができると考えている。また本研究で開発した質量分析イメージングによるラット脳内のboronophenylalanine (BPA)の分布を示す細胞レベルでのイメージングは、ホウ素中性子捕捉療法の薬剤開発などにおけるさらなる発展に貢献できると考えている。脳脊髄液投与法は、さらに中性子照射場で実験動物による実証実験を重ね、人の臨床へと繋げていきたい。