Development of Neutron Capture Therapy using intra-nucleus Gadolinium delivery to refractory scirrhous carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19520
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Yanagie Hironobu 東京大学, 大学院工学系研究科(工学部), 客員研究員 (30212278)
• Co-Investigator(Kenkyū-buntansha): 高橋 浩之 東京大学, 大学院工学系研究科(工学部), 教授 (70216753)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 中性子捕捉療法 / ガドリニウム化合物 / ボロン化合物 / Polyplex / エレクトロポレーション / 腫瘍内局所投与法 / ヒアルロン酸 / プロタミン

Outline of Final Research Achievements

Gadolinium neutron capture therapy (GdNCT) is one of the particle therapy by the reaction with gadolinium atom (Gd) and the thermal neutron. Gd induces cell cytotoxic effects by the Auger electron which is high LET of range 1μm and gamma rays of few mm ranges by reacting with a thermal neutron. We applied cationic liposome, and cationic polymer, as the Gd delivery system. We prepared Gadolinium-Polyplex; Gd-plex (Gd / hyaluronic acid / protamine-mixed with cationic liposome). The increase effect of AsPC-1 human pancreatic tumour growth suppression was recognized in the Gd-plex or Gd-PEI treated groups with thermal neutron irradiation.　Hyalinizations with significant degenerations were seen in the irradiation group, and apoptosis was thought as one of the mechanism of tumor growth suppression. We had the augumentation effect of tumour growth suppression by GdNCT using electroporation. We hope to apply to the intensive treatments for pancreatic cancers and hepatic cancers.

Free Research Field

腫瘍治療学、中性子捕捉療法、ドラッグデリバリーシステム

Academic Significance and Societal Importance of the Research Achievements

GdNCTの治療効果増強を目指して、Gd-polyplexを形成させ腫瘍内投与法を用いた、熱中性子照射による抗腫瘍効果を提唱している。
Gd-plexやBoro-plexを用いた中性子捕捉剤の癌細胞内デリバリーシステムの開発は、膵臓癌に対する超音波内視鏡下穿刺法や、肝臓癌に対するWOWエマルション封入肝動注法を用いての加速器中性子捕捉療法への応用が考えられ、集学的癌治療の新たな展開が期待できる。