Translational research and protocol planning for boron neutron capture therapy for central nervous system primary lymphoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24055
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka Medical College
• Principal Investigator: Takeuchi Koji 大阪医科大学, 医学部, 非常勤医師 (40804109)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: BNCT / malignant lymphoma / PCNSL / 悪性リンパ腫 / BPA / PET

Outline of Final Research Achievements

Primary central nervous system lymphoma (PCNSL) is a refractory brain tumor with a very high relapse rate. PCNSL has a high relapse rate after standard treatment of high-dose methotrexate (HD-MTX) and whole brain radiotherapy (WBRT), and a new treatment strategy is urgently required. Boron neutron capture therapy (BNCT), a tumor cell selective therapy has the potential to overcome these difficulties. On in vitro cellular uptake using boronophenylalanine (BPA), and in vivo biodistribution for mouse PCNSL models using systemic administration of BPA were conducted and showed that boron uptakes were confirmed in cells and brain tumors, respectively. On in vivo neutron irradiation study showed that BNCT group had a significantly prolonged survival compared to control groups. BNCT seems to be a promising treatment method and we will go ahead to propose a clinical BNCT protocol.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

PCNSLは、高用量メトトレキサート(HD-MTX)と全脳照射による初期治療への奏功率は高いが、再発率の非常に高い難治性脳腫瘍である。再発時には、HD-MTXは放射線照射歴がある場合使用できず、放射線追加照射には周辺正常脳組織への線量制限のため、治療制限がある。BNCTは腫瘍細胞選択性の高い治療であり、初期治療で治療耐用能の落ちた正常脳組織への影響を軽減し、腫瘍細胞のみを駆逐し得る。本研究では、マウスPCNSLモデルへのBNCTの有用性を示すことができており、次のステップである人を対象とした再発PCNSL治療に対するBNCT臨床試験への足掛かりとなる学術的・社会的意義の高い研究となった。