Development of Cell Selective particle irradiation using epithermal neutron beam for malignant brain tumor.

• Project/Area Number: 17390390
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUMURA Akira University of Tsukuba, Graduate School of Comprehensive Human Science, Professor (90241819)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Tetsuya University of Tsukuba, Graduate School of Comprehensive Human Science, Assistant Professor (30375505) ; SHIBATA Yasushi University of Tsukuba, Graduate School of Comprehensive Human Science, Assistant Professor (50400685) ; KAGEJI Teruyoshi University of Tsukuba, Department of Neurosurgery, Assistant Professor (70294684) ; KUMADA Hiroaki Japan Atomic Energy Agency, Departmentof Research Reactor and TandemAccelerator, Researcher (30354913) ; ISOBE Tomonori University of Tsukuba, Graduate School of Comprehensive Human Science, Assistant Professor (70383643) ; 森田 明夫 東京大学, 医学部附属病院, 助教授 (60302725) ; 藤堂 具紀 東京大学, 医学部附属病院, 講師 (80272566)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥15,810,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥1,410,000); Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2006: ¥4,700,000 (Direct Cost: ¥4,700,000); Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
• Keywords: Glioma / BNCT / Boron / Neutron / Brain Tumor / 脳腫瘍 / BMCT / グリオブラストーマ

Research Abstract

Clinical trial of BNCT for Glioblastoma
Eight patients with histological proven glioblastoma with an average age of 65 years (range 32-76, M:F=2:6) were underwent BNCF with new protocol which add 30Gy X ray irradiation after BNCT. 7 patients were treated with intra-operative BNCT before the protocol. In these 15 cases, 5 cases are alive; the average post BNCT follow up period was 20.3 months. Time to progression was 11.9 months, overall survival was 25.3 months. Adverse event (Grade 3>) were seen in 2 cases; convulsion and brain swelling (1 case) and transient oculomotor palsy (1 case). These result superior to standard treatments and suggest the effectiveness of the BNCT for malignant glioma
MR spectroscopy
For estimating absolute concentration of boron compounds in tissue, proton MR spectroscopy (MRS) was applied to quantify phenylalanine and L-p-boronophenylalanine (BPA). We could identify several characteristic resonances, peak of 7.32ppm (phenylalanine), four peak ranged 7.1 ppm to 7.6 ppm (BPA). A water phantom were used, and absolute concentration were obtained by proton MRS using a tissue water signal as an internal standards. These methods have high correlation between the calculated concentrations based on MRS and the known concentration. (R=0.99: phenylalanine and BPA).
These clinical results appear to encouraging, but the effectiveness of the invading tumor cells are still unclear. Improved tumor targeting boron delivery and neutron distribution will enhance the therapeutic effectiveness of BNCT.
MR spectroscopy results indicate that proton MRS can be non-invasive and potentially useful technique for BPA quantification in BNCT.

Research Products

• [Journal Article] Matsumura A Neutron capture therapy for Glioblastoma (2008)
  • Author(s): Yamamoto T, Nakai K
  • Journal Title: No Shinkei Geka 36 Pages: 293-302
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Boron neutron capture therapy for glioblastoma (2008)
  • Author(s): Yamamoto T, Nakai K, Matsumura A
  • Journal Title: Cancer letters 263 Pages: 253-8
  • NAID: 120006491219
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Combined use of sodium borocaptate and buthionine sulfoximine in boron neutron capture therapy enhanced tissue boron uptake and delayed tumor growth in a rat subcutaneous tumor model (2008)
  • Author(s): Yoshida F, Yamamoto T, Nakai K, Kumada H, Shibata Y, Tsuruta W, Endo K, Tsurubuchi T, Matsumura A
  • Journal Title: Cancer letters 263 Pages: 253-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Boron neutron capture therapy for glioblastoma (2008)
  • Author(s): Yamamoto T, Nakai K, Matsumura A
  • Journal Title: Cancer letters 262 Pages: 143-152
  • NAID: 120006491219
  • Peer Reviewed
• [Journal Article] Dosimetry for Neutron capture Therapy in JRR-4 (2007)
  • Author(s): Kumada H, Yamamoto T
  • Journal Title: Japanese Journal of Health Physics 4281 Pages: 23-37
  • NAID: 110006274271
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] JRR-4における中性子捕捉療法の線量評価 (2007)
  • Author(s): 熊田博明、山本哲哉
  • Journal Title: 保健物理 42 Pages: 23-37
  • NAID: 110006274271
  • Peer Reviewed
• [Journal Article] Demonstration of inter-and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission(Micro-PIXE) (2006)
  • Author(s): Endo K, Yamamoto T, Shibata Y, Tsuboi K, Matsumura A, Kumada H, Yamamoto K, Sakai T, Sato T, Oikawa M, Ohara Y, Ishii K
  • Journal Title: Oncol Res 16 Pages: 57-65
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Demonstration of inter- and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission (Micro-PIXE) (2006)
  • Author(s): Endo K, Yamamoto T, Shibata Y, Tsuboi K, Matsumura A, et al.
  • Journal Title: Oncol Res. 16(2) Pages: 57-65
• [Journal Article] Boron distribution in the normal rat brain after infravenous injection of boronophenylalanine-fructose (2006)
  • Author(s): Shibata Y
  • Journal Title: J Neuro-Oncology (In press)
• [Journal Article] Combination of fractionated photon radiation and BNCT (2006)
  • Author(s): Yamamoto T, Kageji T, Nakai K, Endo K, Matsuda M, Masuda R, Matsumura A
  • Journal Title: Advances in Neutron capture therapy Pages: 37-39
• [Journal Article] A new NEDO research project towards hospital based accelerator BNCT using advanced DDS system (2006)
  • Author(s): Matsumura A, Mori Y, Kaneda Y, Hashimoto K, Nakai K, Yamamoto T, et al.
  • Journal Title: Advances in Neutron capture therapy Pages: 74-76
• [Journal Article] 悪性グリオーマに対する放射線治療の検討 (2006)
  • Author(s): 松田真秀, 山本哲哉, 坪井康次, 高野晋吾, 柴田 靖, 松村 明
  • Journal Title: Neuro-Oncology 15(2) Pages: 45-49
• [Journal Article] Analysis of intracellular distribution of boron and gadolinium in 9L sarcoma cells using a single-ended accelerator (Micro PIXE) (2006)
  • Author(s): Endo K, Nakai K, Yamamoto Y, Shibata Y, Matsumura A, et al.
  • Journal Title: JAEA-Review 2005-001 001 Pages: 316-317
• [Journal Article] Combination of Boron and Gadolinium Compounds for Neutron Capture Therapy. An In Vitro Study. (2005)
  • Author(s): Matsumura A, Zhang T, Nakai K, Endo K, Kumada H, Yamamoto T, Yoshida F, Sakurai F, Yamamoto K, Nose T
  • Journal Title: Clin.Cancer Res. 24 Pages: 207-212
• [Presentation] Prognostic factor of glioblastoma (2008)
  • Author(s): Sakamoto S, Yamamoto T, Takano S, Shibata Y, Nakai K, Matsuda M, Matsumura A
  • Organizer: 25th Annual meetings of the Tsukuba Society for Neurosurgery
  • Year and Date: 2008-02-03
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Analysis of combined BNCT and radiotherapy for Glioblastoma (2007)
  • Author(s): Yamamoto T, Nakai K, Takano S, Matsumura A, Matsuda M, Endo K, Kageji T, Tokuue K, Tsuboi K
  • Organizer: The 20th Annual meeting of Japanese Society for Therapeutic Radiology and Oncology
  • Year and Date: 2007-12-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] High-dose radiation therapy for glioblastoma (2007)
  • Author(s): Yamamoto T, Nakai K, Matsuda M, Takano S, Shibata Y, Tsurubuchi T, Tokuue K, Tsuboi K, Matsumura A
  • Organizer: 5th Meeting of The Asian Society for Neuro-Oncology
  • Place of Presentation: イスタンブール
  • Year and Date: 2007-11-04
• [Presentation] The Result of high Dose radiation therapy with BNCT and proton beam for Glioblastoma (2007)
  • Author(s): Yamamoto T
  • Organizer: The 45th Annual Meeting of Japan Society of Clinical Oncology
  • Year and Date: 2007-10-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Interim results of boron neutron capture therapy and proton therapy for glioblastoma at University of Tsukuba (2007)
  • Author(s): Matsumura A, Yamamoto T, Nakai K, Takano S, Shibata Y, Tsuboi K, Tokuue K
  • Organizer: International Workshop "Clinical trials for BNCT"
  • Place of Presentation: ペッテン
  • Year and Date: 2007-10-11
• [Presentation] Invited lecture. Current clinical results of high-dose radiotherapies for glioblastoma multiforme (2007)
  • Author(s): Yamamoto T
  • Organizer: Young Researcher BNCT Meeting
  • Place of Presentation: Birmingham
  • Year and Date: 2007-09-21
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Invited lecture. Current clinical results of high-dose radiotherapies for glioblastoma multiforme (2007)
  • Author(s): amamoto T
  • Organizer: Young Researcher BNCT Meeting
  • Place of Presentation: バーミンガム
  • Year and Date: 2007-09-21
• [Presentation] Histopathological evaluation of glioblastoma after high-dose radiation therapy (2007)
  • Author(s): Tsurubuchi T, Yamamoto T, Enomoto T, Sato M, Sakamoto N, Matsuda M, Marushima A, Nakai K, Saito A, Shibata Y, Tsuboi K, Matsumura. A
  • Organizer: Young Researcher BNCT Meeting
  • Place of Presentation: Birmingham
  • Year and Date: 2007-09-20
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Proton MR spectroscopy for quantification of 1-phenylalanine (2007)
  • Author(s): Yamamoto Y, Isobe T, Anno I, Yamamoto T, Shibata Y, Matsumura A
  • Organizer: Young Researcher BNCT Meeting
  • Place of Presentation: Birmingham
  • Year and Date: 2007-09-20
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Proton MR spectroscopy for quantification of l-phenylalanine (2007)
  • Author(s): Yamamoto Y, Isobe T, Anno I, Yamamoto T, Shibata Y, Matsumura A.
  • Organizer: Young Researcher BNCT Meeting
  • Place of Presentation: バーミンガム
  • Year and Date: 2007-09-20
• [Presentation] Histopathological evaluation of glioblastoma after high dose radiation therapy (2007)
  • Author(s): Tsurubuchi T, Yamamoto T, Sato H, Sakamoto N, Matsuda M, Marushima A, Nakai K, Saito A, Shibata Y, Takano S, Tsuboi K, Matsumura A
  • Organizer: 4th Congress on Neutron Capture Therapy
  • Year and Date: 2007-08-25
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Protocol and current result of glioblastoma (2007)
  • Author(s): Yamamoto T, Matsuda M, Tsuboi K, Takano S, Takada T, Shibata Y, Matsumura A, Tokuue K, Akine Y
  • Organizer: 25th Annual meetings of the Tsukuba Society for Neurosurgery
  • Year and Date: 2007-02-04
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Clinical results of Glioblastoma treatment before and after the adoption of BNCT and proton beam irradiation (2007)
  • Author(s): Yamamoto T, Matsuda M, Endo K, Nakai K, Tsuboi K, Takano S, Shibata Y, Matsumura A, Tokuue K, Akine Y, Kageji T, Kumada H, Kisi T
  • Organizer: Scientific meeting of medical treatment system using neutron beam and particle irradiation
  • Year and Date: 2007-02-04
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Non-invasive measurement of p-Boronophenylalanine using proton MR Spectroscopy (2007)
  • Author(s): Isobe T, Matsumura A, Anno I, Shibata Y, Yamamoto T, Hirano Y, Ozaki M, Fujibuchi T, Isobe T, Muraishi H, Yoda K, Umeda T
  • Organizer: Rep. of China Japan Korea International Joint conference for radiological technologists
  • Place of Presentation: Taipei
  • Year and Date: 2007-01-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] High-dose radiation therapy for glioblastoma (2007)
  • Author(s): Yamamoto T, Nakai K, Matsuda M, Takano S, Shibata Y, Tsurubuchi T, Tokuue K, Tsuboi K, Matsumura A
  • Organizer: 5th Meeting of The Asian Society for Neuro-Oncology
  • Place of Presentation: Instanbul
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Histopathological evaluation of glioblastoma after high-dose radiation therapy (2007)
  • Author(s): Tsurubuchi T, Yamamoto T, Enomoto T, Sato M, Sakamoto N, Matsuda M, Marushima A, Nakai K, Saito A, Shibata Y, Tsuboi K, Matsumura A
  • Organizer: 5th Meeting of The Asian Society for Neuro-Oncology
  • Place of Presentation: Instanbul
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Simposium : Neutron Capture Therapy for Cancer. "BNCT for Malignant Glioma" (2006)
  • Author(s): Matsumura A, Yamamoto T, Nakai K, Endo K, Matsuda M, Shibata Y, Takano S, Tsuboi K, Kumada H, Kageji T
  • Organizer: 19th Japanese Society for Therapeutic Radiology and Oncology
  • Place of Presentation: Sendai
  • Year and Date: 2006-11-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Particle irradiation for malignant glioma (2006)
  • Author(s): Yamamoto T, Tsuboi K, Takano S, Shibata Y, Matsuda M, Matsumura A, Tokuue K, Akine Y
  • Organizer: 44th Japan Society of Clinical Oncology
  • Place of Presentation: Tokyo
  • Year and Date: 2006-10-18
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Clinical trial of combined BNCT and radiotherapy for Glioblastoma (2006)
  • Author(s): Yamamoto T, Kageji T, Nakai K, Endo K, Matsuda M, Shibata Y, Takano S, Tokuue K, Matsumura A
  • Organizer: 24th Annual Meeting of the Japan Society for Neuro-Oncology
  • Place of Presentation: Akan
  • Year and Date: 2006-10-02
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Analysis of recurrent pattern of the patients who underwent BNCT (2006)
  • Author(s): Masahide Matsuda, Tetsuya Yamamoto, Kei Nakai, Kiyoshi Endo, Yasushi Shibata, Shingo Takano, Akira Matsumura
  • Organizer: 65th Annual Meeting of the Japanese Neurosurgical Society
  • Year and Date: 2006-09-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] BNCT using JRR-4 and future plan (2006)
  • Author(s): Yamamoto T, Matsuda M, Nakai K, Endo K, Matsumura A
  • Organizer: Scientific meeting of medical treatment system using neutron beam and particle irradiation
  • Year and Date: 2006-02-25
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Combination of fractionated photon radiation and BNCT (2006)
  • Author(s): Tetsuya Yamamoto, Teruyoshi Kageji, Kei Nakai, Kiyoshi Endo, Masahide Matsuda, Rhosuke Masuda, Akira Matsumura
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Failure Patterns of high-grade glioma treated with BNCT (2006)
  • Author(s): Masahde Matsuda, Tetsuya Yamamoto, Kei Nakai, Kiyoshi Endo, Hiroaki Kumada, Teruyoshi Kageji, Akira Matsumura
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 20lTl/99mTc-MIBI SPECT to evaluate therapy effect of BNCT with BSH and BPA for malignant brain tumor (2006)
  • Author(s): Yasushi Shibata, Wataru Katayama, Tetsuya Yamamoto, Kei Nakai, Kiyoshi Endo, Masahide Matsuda, Akira Matsushita, Akira Matsumura
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A new NEDO research project towards hospital based accelerator BNCT using advanced DDS system (2006)
  • Author(s): Akira Matsumura, Yoshihiro Mori, Yasufumi Kaneda, Kazuyuki Hashimoto, Kei Nakai, Tetsuya Yamamoto, Hiroyuki Nakamura, Ken Akamatsu, Thmoyuki Asano, Senman Lee, Yoshinori Sakurai, Hiroyuki Kumada, Kazuyoshi Yamamoto, Yasushi Shibata, Tokushi Shibata, Toro Nakahara, Masafumi Mutoh, Hisaharu Sakae, Yoshimasa Yuasa, Yasuo Satoh,Hiroaki Sakurabata, Satoshi Muraki, Takahisa Nagayama
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Effects of combined treatment using sodium borocaptate(BSH) and buthionine sulfoximide(BSO) in a rat tumor model (2006)
  • Author(s): Fumiyo Yoshida, Tetsuya Yamamoto, Kei Nakai, Yasushi Shibata, Akira Matsumura
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Analysis of born distribution in 9L gliosarcoma cells using particle induced r-ray emission(PIGE) (2006)
  • Author(s): Kiyoshi Endo, Tetsuya Yamamoto, Yasushi Shibata, Koji Tsuboi, Akira Matsumura, Hiroaki Kumada, Kazuyoshi Yamamoto, Takuro Sakai, Takahiro Sato, Masakazu Oikawa, Yoshihiro Ohara, Keizo Ishii
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Boron distribution in normal and impaired vascular tissue (2006)
  • Author(s): Wataro Tsuruta, Tetsuya Yamamoto, Kei Nakai, Fumiyo Yoshida, Kiyoshi Endo, Takao Tsurubuchi, Akira Matsumura
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Application of HVJ envelope system to boron neutron capture therapy(BNCT) (2006)
  • Author(s): Kei Nakai, Tetsuya Yamamoto, Akira Matsumura, Masaaki Kurooka, Yasufumi Kaneda, Tomoyuki Asano
  • Organizer: 12th International congress on neutron capture therapy
  • Place of Presentation: Kagawa
  • Description: 「研究成果報告書概要(欧文)」より