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Preclinical study of neutron capture therapy for malignant brain tumors using newly developed BPA delivatives

Research Project

Project/Area Number 10470288
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

TAKAGAKI Masao  Kyoto University, Research Reactor Institute, Assistant, 原子炉実験所, 助手 (70252533)

Co-Investigator(Kenkyū-buntansha) KIRIHATA Mitsunon  Osaka Preferectural University, Dept.Agriculture, Professor, 農学部, 教授 (60128767)
KOBAYASHI Toru  Kyoto University, Research Reactor Institute, Associate Professor, 原子炉実験所, 助教授 (90089136)
ONO Koji  Kyoto University, Research Reactor Institute, Professor, 原子炉実験所, 教授 (90122407)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsMalignant brain tumors / Neutron capture therapy / Boron / BPA delivatives / Preclinical study / 活性相関
Research Abstract

The various derivatives which were removed the side chains which were a carboxyl group and amino group in turn were composed while keeping water-solubility of BPA for a purpose to improve BNCT effect for malignant brain tumors by modifying Boronophenylalanine (BPA), and their BNCT effect and correlative biological activity were examined using tumor models (in-vivo BNCT) and/or tumor cell lines (in-vitro BNCT). As a result, it was found that p-boronophenylalaninole (BPAol) which a carboxyl group of BPA was exchanged with hydroxymethyl group was revealed the highest BNCT effect. So DL-BPAol was composed, and BNCT were done using melanoma bearing hamsters. As a result, it was found that the tumor growth could be completely controlled for more than 20 days after BNCT, and some time complete healing could be observed. The D-and L-BPAol which were chemical mirror form of BPAol were composed, and their tumor cell killing effect were examined. It was found that BNCT effect was reinforced with D-BPAol although being deteriorated in L-BPAol adversely, and furthermore tumor cell killing effect was reinforced as well. It was already confirmed that DL-BPAol did not show the strong cell toxicity, but the toxicity could be reduced more by making it in D-form. B-10 enriched form of D-BPAol is composed currently in order to confirm a treatment effect in in-vivo. These data was presented in 9^<th> International Symposium on Neutron Capture Therapy for Cancer held in Osaka, November, 2000.
In this study, it was found that D-BPAol was extremely promising agent as a boron carrier for a neutron capture therapy.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] M.Takagaki,K.Ono,T.Kobayashi, et al.: "^<10>B quantitative determination in the ppb range by particle tracks reading for boron neutron capture therapy"J Radioanalytical and Nuclear Chemistry. 247. 389-392 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M,Takagaki,K.Ono,B.F.Spielvogel, et al.: "Boronated dipeptide boronotrimethylglycylphenylalanine as a potential boron carrier in boron neutron capture therapy"Radiation Research. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takagaki,K.Ono,S.Masunaga, et al.: "Alpha amino alchohol of p-boronophenylalanine, BPAol, as a potential boron carrier for BNCT"9^<th> ISNCT abstract. 245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kobayashi,Y.Sakurai,K.Kanda, et al.: "The remodeling and basic characteristics of the heavy water neutron irradiation facility of thye Kyoto University Research Reactor, minly for neuton capture therapy."Nuclear Technology. 131. 354-378 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ozaki,T.Nakano,M.Kirihata, et al.: "Synthesis and biological evolution of p-boronophenylalanine derivatives"Amino Acids. 17(1). 113 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Oda,Y.Kang,M.Takagaki, et al.: "Recent result of BNCT for malignant gliomas in Kyoto University Reactor (KUR)."Proceedings,11^<th> European Congress of Neurosurgery. 269-272 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takagaki, K.Ono, T.Kobayashi, et al.: "^<10>B quantitative determination in the ppb range by particle tracks reading for boron neutron capture therapy."J Radioanalytical and Nuclear Chemistry. 247. 389-392 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takagaki, K.Ono, B.F.Spielvogel, et al.: "Boronated dipeptide boronotrimethyl-glycylphenylalanine as a potential boron carrier in boron neutron capturre therapy."Radiation Research. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takagaki, K.Ono, M.Kirihata, et al.: "Alpha amino alcohol of p-boronophenylalanine, BPAol, as a potential boron carrier for BNCT."Abstract of 9^<th> International Symposium for Neutron Capture Therapy for Cancer.. 245. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kobayashi, Y,Sakurai, K.Kanda, et al.: "The remodeling and basic characteristics of the heavy water neutron irradiation facility of the Kyoto University research Reactor, mainly for neutron capture therapy."Nuclear Technology. 131. 354-378 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Ozaki, T.Nakano. M.Kirihata. et al.: "Synthesis and biological comvolution of p-boronophenylalanine delivatives."Amino Acid. 17(1). 13 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Oda, Y.Kang, M.Takagaki, et al.: "Recent result of BNCT for malignant gliomas in Kyoto University Reactor (KUR)."Proceedings, 11^<th> European Congress of Neurosurgery. 269-272 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takagaki,K.Ono,T.Kobayashi, et al.: "^<10>B quantitative determination in the ppb range by particle tracks reading for boron neutron capture therapy"J Radioanalytical and Nuclear Chemistry. 247. 389-392 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Takagaki,K.Ono,B.F.Spielvogel, et al.: "Boronated dipeptide boronotrimethylglycylphenylalanine as a potential boron carrier in boron neutron capture therapy"Radiation Research (in press). in-press. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Takagaki,K.Ono,S.Masunaga, et al.: "Alpha amino alchohol of p-boronophenylalanine, BPAol, as a potential boron carrier for BNCT"9^<th> ISNCT abstract. 245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kobayashi,Y.Sakurai,K.Kanda, et al.: "The remodeling and basic characteristics of the heavy water neutron irradiation facility of thye Kyoto University Research Reactor, minly for neuton capture therapy."Nuclear Technology. 131. 354-378 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Ozaki,T.Nakano,M.Kirihata, et al.: "Synthesis and biological cvolution of p-boronophenylalanine derivatives"Amino Acids. 17(1). 113 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Oda,Y.Kang,M.Takagaki,et al.: "Recent result of BNCT for malignant gliomas in Kyoto University Reactor (KUR)"Proceedings of 11^<th> European Congress of Neurosurgery. 269-272 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Ozaki,T.Nakano,M.Kirihata,M.Takagaki: "Synthesis and biological evolution of p-boronophenylalanine derivatives"Amino Acids. 17(1). 113 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ono,S.Masunaga,M.Suzuki,Y.Kinashi,M.Takagaki,M.Akaboshi: "The combined effect of boronophenylalanine and borocaptate in boron neutron capture therepy for SCCVVII tumor in mice"Int J Radiat Oncol Biol Phys. 43(2). 431-436 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Nakano, M.Nishiaki, M.Takagaki, K.Ono, Y.Kitaoka and M.Kirihata: "p-Boronophenylalaninol(BPA-OL)and its congeners: Synthesis and b〓 properties" Eighth International Symposium on Neutron Capture Therapy for Cancer, abstracts. 47 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kobayashi, Y.Sakurai and M.Ishikawa: "Real-time absorbed dose estimation system for BNCT by PG-SPECT" Eighth International Symposium on Neutron Capture Therapy for Cancer, abstracts. 141 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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