Development of neutron capture therapy using intra-arterial injection of cancer specific emulsion by membrane emulsification technique

• Project/Area Number: 24390311
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Yanagie Hironobu 東京大学, 工学(系)研究科(研究院), 研究員 (30212278)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Hiroyuki 東京大学, 大学院工学系研究科(工学部), 教授 (70216753)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 中性子捕捉療法 / ボロン化合物 / ガドリニウム化合物 / ＷＯＷエマルション / エストロゲン骨格 / 二段階肝動注ターゲティング法 / 腫瘍マーカー / 肝臓癌と乳癌 / ＢＰＡ / 腫瘍血管 / ＢＳＨ / 二段膜乳化法 / BPA / ターゲティング / WOWエマルション / モノクローナル抗体

Outline of Final Research Achievements

The purpose of this project is to develop a novel tumor selective emulsion for applicating boron neutron capture therapy(BNCT). We had been able to achieve 170/58.3 ppm in 24hrs/72hrs, respectively, which was exceeded more than 30ppm, as the effective boron concentration for BNCT in VX-2 rabbit hepatic tumour model. Apoptosis was recognized in the tumour by BNCT after intra-arterial hepatic injection of 10BSH entrapped WOW emulsion. Cancer cell cytotoxicity of mouse breast cancer cell line was recognized by BNCT using natural boron binding estrogen compound, and this cytotoxicity was lower than the effect using 10Borono-phenylalanine(BPA). These results showed that it was more effective to develop the cancer selective accumulating compounds as second targeting than to develop the cancer selective modification of surface of WOW emulsion as first targeting.

Research Products

• [Journal Article] Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a ^<10>BSH-containing WOW emulsion (2014)
  • Author(s): Yanagie H, Higashi S, Seguchi K, Ikushima I, Fujihara M, Nonaka Y, Oyama K, Maruyama S, Hatae R, Suzuki M, Masunaga S, et al. 計23名
  • Journal Title: Appl Radiat Isot Volume: 72 Pages: 21-29
  • DOI: 10.1016/j.apradiso.2014.01.014
  • Peer Reviewed
• [Journal Article] Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agen (2013)
  • Author(s): N. Dewi, H. Yanagie, H. Zhu, K. Demachi, A. Shinohara, K. Yokoyama, M. Sekino, Y. Sakurai, Y. Morishita, N. Iyomotog, T. Nagasaki, Y. Horiguchi, Y. Nagasaki, J. Nakajima, K. Ono, K.Kakimi, H.Takahashi
  • Journal Title: Biomed. Biopharmacother. Volume: 67 Issue: 6 Pages: 451-457
  • DOI: 10.1016/j.biopha.2012.11.010
  • Peer Reviewed
• [Journal Article] Pilot Clinical Study of Boron Neutron Capture Therapy for Recurreced Hepatic Cancer-using Intra-Arterial Injection of 10BSH Entrapped wow Emulsion (2013)
  • Author(s): Yanagie H, et al.
  • Journal Title: Applied Radiation & Isotopes Volume: (in press)
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer (2012)
  • Author(s): Sumitani S, Yanagie H, Nagasaki y, et al.
  • Journal Title: Biomaterials. Volume: 33 Pages: 3568-77
  • NAID: 120007130664
  • Peer Reviewed
• [Presentation] Translational Research of Boron Neutron Capture Therapy to Hepato- cellular Carcinoma with Intra-arterial Boron Delivery using WOW emulsion (2015)
  • Author(s): Yanagie H, Takahashi H.,et al
  • Organizer: The 1st Academic Meeting of Taiwan Society of Neutron Capture Therapy
  • Place of Presentation: San-Xia New Taipei City, Taiwan
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] 原発性肝臓癌に対する中性子捕捉療法に応用するWOWエマルションについての検討 (2015)
  • Author(s): 柳衛宏宣、高橋浩之、他
  • Organizer: 第12回日本中性子捕捉療法学会
  • Place of Presentation: 兵庫県、神戸、神戸学院大学
  • Year and Date: 2015-09-05
• [Presentation] 再発乳癌への中性子捕捉療法の応用に向けた熱中性子線ドジメタリーの検討 (2015)
  • Author(s): 柳衛宏宣、高橋浩之、他
  • Organizer: 第12回日本中性子捕捉療法学会
  • Place of Presentation: 兵庫県、神戸、神戸学院大学
  • Year and Date: 2015-09-04
• [Presentation] Translational Research of Boron Neutron Capture Therapy for Primary Hepatocellular Carcinima with Intra-artetial Injection of Boron Entrapped WOW Emulsion (2015)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: The 6th Asia Pacific Primary Liver Cancer Expert Meeting(APPLE)
  • Place of Presentation: HYATT REGENCY OSAKA,Osaka,JAPAN
  • Year and Date: 2015-07-04
  • Int'l Joint Research
• [Presentation] Experiences of Tumour Growth Suppression with Boron Delivery Systems in Rabbit Hepatic Cancer Model for Neutron Capture Therapy (2015)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: ICRR2015
  • Place of Presentation: Kyoto International Conference Center,Kyoto, JAPAN
  • Year and Date: 2015-05-28
  • Int'l Joint Research
• [Presentation] Application of Neutron Capture Auto-Radiography for Detection of Boron Delivery of Neutron Capture Therapy (2015)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: 東京大学医学部付属病院先端医療シーズ開発フォーラム2015
  • Place of Presentation: 東京大学伊藤国際学術センター、東京
  • Year and Date: 2015-01-22
• [Presentation] Detection of Local Recurrenced Breast Cancer by Boron Uptake in Tumour by 18F-BPA Positron Emission Tomograpy for Application to Boron Neutron Capture Therapy (2014)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: EANM'14 - Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Gothenburg, SWEDEN
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] BNCTによる集学的がん放射線治療 (2014)
  • Author(s): 柳衛宏宣
  • Organizer: 第12回化学放射線治療科学研究会
  • Place of Presentation: 東京大学医学部附属病院、東京
  • Year and Date: 2014-07-29
  • Invited
• [Presentation] 一般外科領域における中性子捕捉療法の臨床経験と今後の展望 (2014)
  • Author(s): 柳衛宏宣、他
  • Organizer: 第11回日本中性子捕捉療法学会
  • Place of Presentation: 大阪大学 大阪
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] Tumor growth suppression by neutron capture therapy using Gd-DTPA-incorporated calcium phosphate nanoparticles as gadolinium drug agent (2014)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 第11回日本中性子捕捉療法学会
  • Place of Presentation: 大阪大学 大阪
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] Clinical Experiences of Boron Neutron Capture Therapy to Recurrenced Rectal Cancers (2014)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: 16th International Conference on Neutron Capture Therapy
  • Place of Presentation: Helsinki, FINLAND
  • Year and Date: 2014-06-14 – 2014-06-19
• [Presentation] In vivo evaluation of Gd-DTPA-incorporated calcium phosphate nanoparticles for neutron capture therapy agent (2014)
  • Author(s): N. Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 16th International Conference on Neutron Capture Therapy
  • Place of Presentation: Helsinki, FINLAND
  • Year and Date: 2014-06-14 – 2014-06-19
• [Presentation] Feasible evaluation of WOW emulsion as intra-arterial boron delivery (2014)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: 16th International Conference on Neutron Capture Therapy
  • Place of Presentation: Helsinki, FINLAND
  • Year and Date: 2014-06-14 – 2014-06-19
• [Presentation] Application of Boron Neutron Capture Therapy for Intensive Treatmentsto Recurreced Gastro-intestinal Cancers (2014)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: 1st KURII International Workshop on Neutron Capture Therapy
  • Place of Presentation: Osaka, Japan
• [Presentation] 中性子捕捉療法のがん治療への応用展開 (2014)
  • Author(s): 柳衛宏宣
  • Organizer: FIRST Joint International Symposium
  • Place of Presentation: 東京大学 東京
  • Invited
• [Presentation] 三元複合体を用いた胃癌細胞への遺伝子デリバリーシステムの検討 (2013)
  • Author(s): 柳衛宏宜、等
  • Organizer: 第86回日本胃癌学会総会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 2013-02-28
• [Presentation] 直腸癌骨盤内再発腫瘍への中性子捕捉療法の臨床経験 (2013)
  • Author(s): 柳衛宏宜、高橋浩之、等
  • Organizer: 平成24年度京都大学原子炉実験所専門研究会
  • Place of Presentation: 熊取町、大阪府
  • Year and Date: 2013-02-16
• [Presentation] 原発性肝細胞癌に対する中性子捕捉療法への応用に向けたポロン封入WOW エマルジョンシステムの検討 (2013)
  • Author(s): 柳衛宏宜、高橋浩之, 等
  • Organizer: 東京大学先端医療シース開発フォーラム
  • Place of Presentation: 東京大学国際学術研究センター、東京(招待講演)
  • Year and Date: 2013-01-25
• [Presentation] 中性子捕捉療法におけるボロンデリバリーシステム検出への中性子ラジオグラフィーの基礎的検討 (2013)
  • Author(s): 柳衛宏宜、高橋浩之, 等
  • Organizer: 平成24年度京都大学原子炉実験所 中性子イメージング専門研究会
  • Place of Presentation: 熊取町、大阪府(招待講演)
  • Year and Date: 2013-01-09
• [Presentation] 直腸癌骨盤内再発腫瘍に対する中性子捕捉療法の臨床経験 (2013)
  • Author(s): 柳衛宏宣、高橋浩之、他
  • Organizer: 第10回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 岡山県岡山市
• [Presentation] Application of Liposomal Gadolinium Delivery in Neutron Capture (2013)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 第10回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 岡山県岡山市
• [Presentation] Basic Research of WOW Emulsion to Hepatic Cancer including Application for BNCT (2013)
  • Author(s): Yanagie H, Takahashi H.,et al.
  • Organizer: 6th BNCT Trilateral Meeting
  • Place of Presentation: Taipei, Taiwan
  • Invited
• [Presentation] Application of Gadolinium Drug Delivery in Neutron Capture Therapy: (2013)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 7th Young Researchers Meeting on NCT
  • Place of Presentation: Granada, Spain
• [Presentation] Novel Arterial-Injection-Chemotherapy using Epirubicin Entrapped WOW Emulsion for Hepatocellular Carcinoma (2013)
  • Author(s): Yanagie H, Takahashi H., et al.
  • Organizer: 3rd International Conference on Multifunctional, Hybrid and N anomate rials
  • Place of Presentation: Sorrento, Italy
• [Presentation] Experiences of Pilot Clinical Study on Boron Neutron Capture Therapy Resureced Gastrointestixlal Cancers (2012)
  • Author(s): Yanagie H, Takahashi H., et al.
  • Organizer: 4^<th> BNCT Trilateral Meeting (invited)
  • Place of Presentation: National Tsing Hua Univer sity, Hainchu, Taiwan
  • Year and Date: 2012-12-18
• [Presentation] BNCT (ホウ素中性子捕捉療法)を施行した直腸癌仙骨再発の1例 (2012)
  • Author(s): 波多江亮、柳衛宏宜, 等
  • Organizer: 第25回多摩大腸疾患懇話会
  • Place of Presentation: 立川市、東京都
  • Year and Date: 2012-11-10
• [Presentation] Tumour Growth Suppression with Intra-arterial Administration of BSH Entrapped Transferrin Binding PEG Liposome as Selective Boron Carrier in vx-2 Rabbit Hepatic Cancer Model 10r Neutron Capture Therapy (2012)
  • Author(s): Yanagie H, Takahashi H., et al.
  • Organizer: 15^<th> International Conference of Neutron Capture Therapy
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2012-09-13
• [Presentation] In Vivo Study of Gadolinium-based Neutron Capture Therapy (2012)
  • Author(s): Novriana D, Yanagie H, Takahashi H., et al.
  • Organizer: 15^<th> International Conference of Neutron Capture Therapy
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2012-09-13
• [Presentation] Planning of Neutron Capture Therapy for Local Recurrenced Breast Cancer According to Estimation of Boron Uptake in Tumour by FBPA Positron Emission Tomograpy (2012)
  • Author(s): Yanagie H, Takahashi H., et al.
  • Organizer: 15^<th> International Conference of Neutron Capture Therapy
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2012-09-13
• [Presentation] Pilot Clinical Study of Boron Neutron Capture Therapy for Recurreced Hepatic Cancer and Gastric Cancer (2012)
  • Author(s): Yanagie H, Takahashi H., et al.
  • Organizer: 15^<th> International Conference of Neutron Capture Therapy
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2012-09-10
• [Presentation] 集学的癌治療に向けた中性子捕捉療法の応用展開
  • Author(s): 柳衛宏宣
  • Organizer: 明治薬科大学 がんプロフェッショナル養成基盤推進事業講演会
  • Place of Presentation: 東京都清瀬市
  • Invited
• [Book] 放射線治療と医学物理 (2013)
  • Author(s): 柳衛宏宣、中村浩之、（分担執筆
  • Total Pages: 200
  • Publisher: 養賢堂
• [Book] システム創成サイエンス入門シリーズ : 中性子捕捉療法における薬剤送達システム (2013)
  • Author(s): 柳衛宏宜、中村浩之, 等
  • Publisher: 養賢堂(in press)
• [Book] Textbook of Neutron Capture Therapy, (2012)
  • Author(s): Yanagie H, et al.
  • Total Pages: 553
  • Publisher: Springer, Berlin, Germany