Elucidating the cause of the heterogeneous distribution of boron drugs used for boron neutron capture therapy

Research Project

Project/Area Number	17H06811
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Radiation science
Research Institution	Kyoto University
Principal Investigator	Tsubasa Watanabe 京都大学, 複合原子力科学研究所, 助教 (30804348)
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	ホウ素中性子捕捉療法 / BNCT / L-BPA / 腫瘍組織内薬剤不均一分布 / ホウ素中性子補足療法 / 癌 / 粒子線治療
Outline of Final Research Achievements	We examined the distribution of 4-Borono-L-phenylalanine (L-BPA), which is mainly used for boron neutron capture therapy, in the tumor tissue. Syngeneic mice tumor cell lines, T3M4, was used to analyse the distribution of L-BPA in the tumor tissue. The summary of our findings are as follows: (1) The distribution of the L-type amino acid transporter (LAT1) was homogeneous in the tumor tissue of our mice model regardless of necrotic area and vascular structures. (2) L-BPA can reach even in the area with poor vascular structures. (3) L-BPA distribution of the tumor parenchyma was similar to that of inside the blood vessel.
Academic Significance and Societal Importance of the Research Achievements	本研究成果は、4-Borono-L-phenylalanine (L-BPA)を主に臨床の場でも用いるホウ素中性子捕捉療法の治療抵抗性を考える上で重要な知見であると考える。従来、血流の違い・低酸素領域・がん細胞それぞれのアミノ酸要求やアミノ酸トランスポーターの発現の程度の違いなどに影響され、腫瘍組織内でのL-BPAの分布は著しく不均一ではないかと予想されていた。しかし、我々が用いたマウスモデルでの結果によると予想に反してL-BPAは腫瘍組織内で比較的均一に分布していることがわかった。