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X線低感受性腫瘍に対する中性子捕捉療法の基礎研究

Research Project

Project/Area Number 12217065
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

小野 公二  京都大学, 原子炉実験所, 教授 (90122407)

Co-Investigator(Kenkyū-buntansha) 木梨 友子  京都大学, 原子炉実験所, 助手 (80252534)
櫻井 良憲 (桜井 良憲)  京都大学, 原子炉実験所, 助手 (20273534)
切畑 光統  大阪府立大学, 農学部, 教授 (60128767)
笠岡 敏  広島国際大学, 薬学部, 助手 (90338690)
高垣 政雄  藍野学院短期大学, 講師 (70252533)
今掘 良夫  京都府立医科大学, 医学部, 助教授 (80191899)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥47,600,000 (Direct Cost: ¥47,600,000)
Fiscal Year 2004: ¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2003: ¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2002: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2001: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2000: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywords悪性神経膠腫 / BSH / BPA / BPA-ol / 再発頭頸部癌 / 耳下腺癌 / 肝臓癌 / HPRT遺伝子 / 中性子捕捉療法 / 硼素化合物 / 突然変異 / スコルビン酸 / BNCT / 熱外中性子 / 肝腫瘍 / 骨肉腫 / Q細胞
Research Abstract

1.BSH 5g+BPA 250mg/kgと熱外中性子によるGB/AAのBNCTでは、>80%の例で体積が>50%縮小し、CR例も得られた。腫瘍縮小効果の発現は全例で<1週間であった。再発は殆どGTV最深部から生じ制御には>45Gy-Eqが必要と判明した。そこで、線量の増加と腫瘍,選択性が高めるためBSHとBPA大量700mg/kgを併用するBNCTを実施中である。2.治療後再発頭頸部癌にBNCTによる再治療を試み、全症例で顕著な腫瘍退宿が得られた。特に耳下腺癌全例(5例)でCRまたはそれに近い効果を得た。近接皮膚を含む正常組織には殆ど反応を惹起しなかった。BNCTの腫瘍細胞選択的照射の特性が明瞭に示された。腫瘍硼素濃度の上昇を狙って動注投与の試験を開始した。3.X線照射やBPA-BNCTを受けた腫瘍ではBSHの腫瘍濃度が50%程度高くなることが分った。ラット肝腫瘍モデルでBSH+リピオドールの混液を肝動注すると、塞栓効果で>200ppmの腫瘍硼素濃度と>20の腫瘍:正常肝硼素濃度比が得られた。正常肝線量<50%耐容量、腫瘍線量>30Gy-Eqが可能なので、多発性肝癌患者(1例)にBNCTを実施した。4,肝BNCTで硼素濃度モニター用にγテレスコープを開発し応用した。5.アスコルビン酸は高LET放射線である中性子やBNCRのα粒子によるHPRT遺伝子の突然変異誘発を効果的に抑制することが分った。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All 2004 Other

All Journal Article (6 results) Publications (24 results)

  • [Journal Article] Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH) / lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors.2004

    • Author(s)
      Suzuki, M.
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys. 58・3

      Pages: 892-896

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intra-arterial Administration of Sodium Borocaptate (BSH)/Lipiodol Emulsion Delivers B-10 to Liver Tumors Highly Selectively forBoron Neutron Capture Therapy, Experimental studies in the Rat Liver Model2004

    • Author(s)
      Suzuki, M
    • Journal Title

      Int.J.Radiat.Oncol.Biol.Phys. 59・1

      Pages: 260-266

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.2004

    • Author(s)
      Obayashi, S
    • Journal Title

      Oral Oncol. 40・5

      Pages: 474-482

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ascorbic acid reduced mutagenicity at HPRT locus in CHO cells against thermal neutron radiation.2004

    • Author(s)
      Masunaga, S.
    • Journal Title

      Applied Radiation and Isotopes, S. 61

      Pages: 929-932

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The usefulness of 2-nitroimidazole-sodium borocaptate-^<10>B conjugates as ^<10>B-carriers in boron neutron capture therapy2004

    • Author(s)
      Masunaga, S.
    • Journal Title

      Applied Radiation and Isotopes 61

      Pages: 953-958

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The irradiation system and dose estimation joint-system for NCT wider application in Kyoto University.2004

    • Author(s)
      Sakurai, Y
    • Journal Title

      Applied Radiation and Isotopes 61

      Pages: 829-833

    • Related Report
      2004 Annual Research Report
  • [Publications] Masunaga S: "Usefulness of Combined Treatment with Mild Temperature Hyperthermia and/or Tirapazamine in the Treatment of Solid Tumors : its Independence of p53 Status."Cancer Science. 94. 125-133 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masunaga S: "Potential of alpha-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, referring to that of its enantiomers."Journal of Cancer Research and Clinical Oncology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinji Kawabata: "The successful treatment of glioblastoma patients with modified Boron Neutron Capture Therapy. Report of two cases."J Neuro-Oncol.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Minoru Suzuki: "Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors."Int.J.Radiat.Oncol.Biol.Phys.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Minoru Suzuki: "Intra-arterial Administration of Sodium Borocaptate (BSH)/Lipiodol Emulsion Delivers B-10 to Liver Tumors Highly Selectively for Boron Neutron Capture Therapy : Experimental studies in the Rat Liver Model."Int.J.Radiat.Oncol.Biol.Phys.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuo Maruyama: "Intracellular Targeting of Sodium Mercaptoundecahydrododecaborate (BSH) to Solid Tumors by Transferrin-PEG Liposomes, for Boron Neutron-Capture Therapy (BNCT)"J.Controlled Release. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Shin-ichiro Masunaga, Koji Ono: "Signficance of the response of quiescent cell populations within solid tumors in cancer therapy"J. Radiation Res.. 43. 11-25 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Masunaga, K.Ono, A.Takahashi, T.Ohnishi, Y.Kinashi, M.Takagaki: "Radiobiological characteristics of solid tumours depending on the p53 status of the tumour cells, with emphasis on the response of intratumour quiescent cells"European J. Cancer. 38. 718-727 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Masunaga, K.Ono, A.Takahashi, Y.Sakurai, K.Ohnishi, et al.: "Impact of the p53 status of the tumor cells on the effect of reactor neutron beam irradiation, with emphasis on the response of intratumor quiescent cells"Jpn. J. Cancer Res.. 93. 1366-1377 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuko Kinashi, Shin-ichiro Masunaga, Koji Ono: "Mutagenic effect of borocaptate sodium and boronophenylalanine in neutron capture therapy"Int.J.Radiat.Oncol.Biol.Phys.. 54(2). 562-567 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masunaga S, Ono K, Takahashi A, Ohnishi K, et al.: "Usefulness of Combined Treatment with Mild Temperature Hyperthermia and/or Tirapazamine in the Treatment of Solid Tumors : its Independence of p53 Status"Cancer Science. 94. 125-133 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masunaga S, Ono K, Kirihata M, Takagaki M, Sakurai Y, et al.: "Potential of alpha-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, referring to that of its enantiomers"Journal of Cancer Research and Clinical Oncology. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masao Takagaki, Koji Ono, et al.: "10B quantitative determination in the ppm range by particle tracks reading for boron neutron capture therapy"J Radioanalytical and Nuclear Chemistry. 247(2). 389-392 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuko Kinashi, Koji Ono et al.: "Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound"Radiation Medicine. 19(1). 27-32 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masao Takagaki, Koji Ono et al.: "Boronated Dipeptide Borotrimethylglycylphenylalanine as a potential boron carrier in boron neutron capture therapy for malignant brain tumors"Radiation Res.. 156. 118-122 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisataka Kobayashi, Koji Ono, et al.: "Avidin-dendrimer-(1B4M-Gd)254 : A Tumor-Targeting Therapeutic Agent for Gadolinium Neutron Capture Therapy of Intraperitoneal Disseminated Tumor Which Can Be Monitored by MRI"Bioconjugate Chem.. 12. 587-593 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Shinomura, Koji Ono, et al.: "Case Report Anaesthetic management of 27 cases of boron neutron capture therapy for glioblastoma"Anaesthesia. 56. 665-667 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Masunaga, Koji Ono, et al.: "Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors"Int. J. Radiat. Oncol. Biol. Phys.. 51(3). 828-839 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Kinashi,Y.Sakurai,K.Ono, et al.: "Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in chinese hamster ovary (CHO)cells "Radiat.Res.. 154・3. 313-318 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.F.Banth,W.Yang,K.Ono, et al.: "Boron neutron capture therapy of brain tumors enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine"Int.J.Radioat.Oncol.Biol.Phys.. 47・1. 209-218 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Masunaga,K.One,M.Suzuki, et al.: "Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound"Int.J.Radiat,Oncol.Biol.phys,. 46・3. 653-659 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Suzuki,S.Masunaga,K.Ono, et al.: "The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice"Jpn.J.Cancer Res.. 91・10. 1058-1064 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Ono,Y.Kinahi,S.Masunaga,et al.: "The combined effect of electroposation and borocaptate in boron neutron capture therapy for murine solid tumors"Jpn.J.Cancer Res. 91・8. 853-858 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kobagashi,Y,Sakurai,K.kaodo,Y,Fujita,K.Ono: "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・3. 354-378 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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