1999 Fiscal Year Annual Research Report

中性子捕捉療法の術中癌放射線療法への応用に関する国際協力

Research Project

Project/Area Number	11691202
Research Category	Grant-in-Aid for Scientific Research (A)
Section	一般
Research Institution	The University of Tokyo
Principal Investigator	柳衛宏宣東京大学, 医科学研究所, 助手 (30212278)
Co-Investigator(Kenkyū-buntansha)	小野公二京都大学, 原子炉実験所, 教授 (90122407) 小倉紘一日本大学, 生産工学部, 教授 (60059681) 小林久夫立教大学, 原子力研究所, 教授 (10062605) 武田泰隆東京大学, 医科学研究所, 助手 (40163422) 江里口正純東京大学, 医科学研究所, 助教授 (10114406)
Keywords	中性子捕捉療法 / BSH / BPA / 熱中性子 / 熱外中性子 / ドラッグデリバリーシステム / ステルスリポソーム / 医療用原子炉
Research Abstract	中性子捕捉療法(BNCT)を、難治性消化器癌の術中照射に応用するために、世界の医療用原子炉で行われている悪性脳腫瘍、悪性黒色腫のBNCTの技術を検討し国際協力を進めるべく研究を開始した。 1)本年度は^<10>Bの腫瘍中の濃度分布を定量するための研究を、東大医科研、立教大原子炉、京都大原子炉を中心に、スロベニア国JozefStefan研究所、スイス国のPaul Scherror国立研究所、フランス国Saclay研究所との国際共同研究により実施した。研究は主としてImaging Plateおよび個体飛翔検出器(CR39)を用いた^<10>Bの濃度分布定量法の開発、およびマウスに発生させた腫瘍内の^<10>Bの濃度分布の画像化実験を冷・熱中性子ビームおよび高速中性子ビームを用いて実施した。担癌マウスに、^<10>B封入Stealth liposomeを静脈投与後、40μmの全身切片を作製し、CR39に固定し、Neutron capture radiographyを行った。Etching処理として、NaOHを用いるとImagingに適し、生体内の^<10>B原子の分布を検索でき、PEWを用いると、Countingに適し、生体内の^<10>B原子濃度を定量できることを実証した。さらに、^<10>B封入Liposomeをpolyethylene glycolを用いてstealth化することにより、静脈投与後48時間後、さらに60時間後に腫瘍への^<10>B原子の集積が増加していることを確認した。 2)DDSを用いた選択的なBNCTの開発を進めている。我々は、Liposomeの表面をPEGで修飾することにより、細網内皮系による捕捉を回避し、血中滞留性が著しく向上するStealth liposomeを開発した。AsPC-1あるいはColon26担癌マウスに^<10>B封入Stealth liposomeを静脈注射後、60時間経過しても腫瘍内^<10>Bを40ppm以上保つことをPlasma emmision spectroscopyにて確認し、BNCTを行うのに十分量であった。さらに、2x10^<12>n/cm^2の熱中性子を照射し、BNCTを行うと、腫瘍特異的にAsPC-1腫瘍の増殖抑制およびColon26腫瘍の消失を認めた。 3)フィンランド国のHelsinki国立研究所において、5例の悪性脳腫瘍に対するBNCT医療照射を施行した。また、日本国においては京都大原子炉、日本原研原子炉にて、本年度も、悪性脳腫瘍に対し、BSHあるいはBPAを静脈注射後、中性子捕捉療法の医療照射を行い、症例数を増やし治療成績を上げている。 4)平成12年度は、国際BNCT会議が日本で開催されるため、原子力物理学、ボロン化学、薬学、放射線生物学、外科学および放射線治療学の各分野を統合して班会議を開き、臨床応用を目指したい。

Research Products

(29 results)

All Other

All Publications (29 results)

[Publications] H. Yanagie et al.: "Application of 10B entrapped PEG-liposome to boron neutron-capture therapy for pancreatic cancer model in vivo"Neutron Imaging Methods to Detect Defects in Materials. 2. 709-715 (1999)
[Publications] H. Yanagie et al.: "Neutron capture autoradiographic determination of 10B distributions and concentrations in biological samples for boron neutron capture therapy"Nuclear instruments and Methods in Physics research A. 424. 122-128 (1999)
[Publications] H. Yanagie et al.: "Neutron capture autoradiography for the determination of 10B distributions and concentrations in tumor bearing mice"Neutron Radiography, in press.. 6. 581-590 (2000)
[Publications] K. Amemiya, K. Ogura et al.: "Ultra-high resolution radiography using CR-39 solid state track detectors and atomic force microscopy"Nuclear instruments and Methods in Physics research B. 159. 75-80 (1999)
[Publications] K. Ogura, H. Yanagie et al.: "Determination of 10B concentrations in biological samples using neutron capture autoradiography for boron neutron capture therapy"Proceedings of The Second Japan-US Symposium on Advanced in NDT. 323-328 (1999)
[Publications] J. Scvarc, H. Yanagie et al.: "Selective radiography with etched track detectors"Nucl. Instr. Methods B. 152. 115-121 (1999)
[Publications] J. Rant, H. Yanagie et al.: "Some characteristics of neutron capture autoradiography using photoluminescent imaging plates in the detection of ^<10>B distribution in histological samples"Neutron Radiography. 6. 303-310 (2000)
[Publications] H. Kobayashi, et al.: "Basic performance of a neutron sensitive photostimulated luminescence device for neutron radiography"Nucl. Instr. Methods A. 424. 1-8 (1999)
[Publications] H. Kobayashi, et al.: "A correlated study between effective total macroscopic cross section and effective energies for neutron beams of continuous spectra"Nucl. Instr. Methods A. 424. 151-157 (1999)
[Publications] M. Matsubayashi, H. Kobayashi et al.: "Preparation of a beam quality indicator for effective energy determinations of continuous beams : establishment of traceability"Nucl. Instr. Methods A. 424. 165-171 (1999)
[Publications] S. Fujine, H. Kobayashi, et al.: "Development of image techniques for fast neutron radiography in Japan"Nucl. Instr. Method A. 424. 190-199 (1999)
[Publications] H. Kobayashi et al.: "Study for a novel tomography technique using an imaging plate"Nucl. Instr. Method A. 424. 221-228 (1999)
[Publications] M. Tamaki, H. Kobayashi et al.: "Application of imaging plate for fast and epi-thermal neutron radiography"Neutron Radiography, in press. 6. 293-294 (2000)
[Publications] H. Kobayashi, H. Yanagie et al.: "Fast neutron radiography using track detector"Neutron Radiography, in press. 6. 415-422 (2000)
[Publications] H. Kobayashi: "Design and basic character of neutron collimator on radiography"Proc. of the 6th Asian Symposium on Research Reactors. 367-372 (1999)
[Publications] H. Kobayashi et al.: "Proposal of beam quality indicator for effective energy determination of continuum neutron beam"Proc. of the 2nd Japan-US Symposium on Advances in NDT. 18-23 (1999)
[Publications] J. Rant, H. Yanagie et al.: "Detection of ^<10>B distributions in histological samples by NCAR using thermal and cold neutrons and photoluminescent imaging plates"Neutron Imaging Methods to Detect Defects in Materials. 2. 687-694 (1999)
[Publications] H. Iwata, H. Kobayashi et al.: "Neutron-gamma ray radiography using a multi-color luminescent scintillator"Neutron Radiography. 6(in press). 253-260 (2000)
[Publications] H. Kobayashi et al.: "Determination of photo-stimulated luminescence signals from materials by radiation"Nucl. Instr. Method, B. (in press). (2000)
[Publications] H. Kobayashi: "Image quality : Signals and Information (Invited Lecture)"Neutron Imaging Methods to Detect Defects in Materials. 2. 687-694 (1999)
[Publications] H. Kobayashi: "Image Quality : Signal Information [Series of Lecture Neutron Radiography : States of the Art and Future Neutron radiography]"Neutron Radiography. 6(in press). 11-22 (2000)
[Publications] H. Kobayashi: "Beam formation and characterization for neutron radiography"Neutron Radiography. 6(in press). 169-176 (2000)
[Publications] H. Kobayashi: "Study for ETM cross section measurements"Neutron Radiography. 6(in press). 203-210 (2000)
[Publications] H. Kobayashi: "Basics of imaging plate for radiograms"Neutron Radiography. 6(in press). 271-278 (2000)
[Publications] K. Ono et al.: "The Combined Effect of Boronphenylalanine and Borocaptate in Boron Neutron Capture Therapy for SCCVII Tumors in Mice"Int. J. Radiat. Oncol. Biol. Phys.. 43. 431-436 (1999)
[Publications] S. Masunaga, K. Ono. et al.: "Reoxygenation in quescent and total intratumors cells following thermal neutron irradiation with or without ^<10>B compound-compared with that after γ-ray irradiation"Int. J. Radiat. Oncol. Biol. Phys.. 44. 391-398 (1999)
[Publications] 小林久夫: "ラジオグラフィー用検出器の動向とイメージングプレートの発展"放射線と産業. 88. 13-16 (1999)
[Publications] 小林久夫: "中性子イメージングにおけるIPの諸特性"放射線. 25. 53-68 (1999)
[Publications] 小林久夫: "中性子検出用イメージングプレートの特性"放射線. 25. 61-64 (1999)

1999 Fiscal Year Annual Research Report

中性子捕捉療法の術中癌放射線療法への応用に関する国際協力

Principal Investigator

柳衛 宏宣 東京大学, 医科学研究所, 助手 (30212278)

Research Products

[Publications] H. Yanagie et al.: "Application of 10B entrapped PEG-liposome to boron neutron-capture therapy for pancreatic cancer model in vivo"Neutron Imaging Methods to Detect Defects in Materials. 2. 709-715 (1999)

[Publications] H. Yanagie et al.: "Neutron capture autoradiographic determination of 10B distributions and concentrations in biological samples for boron neutron capture therapy"Nuclear instruments and Methods in Physics research A. 424. 122-128 (1999)

[Publications] H. Yanagie et al.: "Neutron capture autoradiography for the determination of 10B distributions and concentrations in tumor bearing mice"Neutron Radiography, in press.. 6. 581-590 (2000)

[Publications] K. Amemiya, K. Ogura et al.: "Ultra-high resolution radiography using CR-39 solid state track detectors and atomic force microscopy"Nuclear instruments and Methods in Physics research B. 159. 75-80 (1999)

[Publications] K. Ogura, H. Yanagie et al.: "Determination of 10B concentrations in biological samples using neutron capture autoradiography for boron neutron capture therapy"Proceedings of The Second Japan-US Symposium on Advanced in NDT. 323-328 (1999)

[Publications] J. Scvarc, H. Yanagie et al.: "Selective radiography with etched track detectors"Nucl. Instr. Methods B. 152. 115-121 (1999)

[Publications] J. Rant, H. Yanagie et al.: "Some characteristics of neutron capture autoradiography using photoluminescent imaging plates in the detection of ^<10>B distribution in histological samples"Neutron Radiography. 6. 303-310 (2000)

[Publications] H. Kobayashi, et al.: "Basic performance of a neutron sensitive photostimulated luminescence device for neutron radiography"Nucl. Instr. Methods A. 424. 1-8 (1999)

[Publications] H. Kobayashi, et al.: "A correlated study between effective total macroscopic cross section and effective energies for neutron beams of continuous spectra"Nucl. Instr. Methods A. 424. 151-157 (1999)

[Publications] M. Matsubayashi, H. Kobayashi et al.: "Preparation of a beam quality indicator for effective energy determinations of continuous beams : establishment of traceability"Nucl. Instr. Methods A. 424. 165-171 (1999)

[Publications] S. Fujine, H. Kobayashi, et al.: "Development of image techniques for fast neutron radiography in Japan"Nucl. Instr. Method A. 424. 190-199 (1999)

[Publications] H. Kobayashi et al.: "Study for a novel tomography technique using an imaging plate"Nucl. Instr. Method A. 424. 221-228 (1999)

[Publications] M. Tamaki, H. Kobayashi et al.: "Application of imaging plate for fast and epi-thermal neutron radiography"Neutron Radiography, in press. 6. 293-294 (2000)

[Publications] H. Kobayashi, H. Yanagie et al.: "Fast neutron radiography using track detector"Neutron Radiography, in press. 6. 415-422 (2000)

[Publications] H. Kobayashi: "Design and basic character of neutron collimator on radiography"Proc. of the 6th Asian Symposium on Research Reactors. 367-372 (1999)

[Publications] H. Kobayashi et al.: "Proposal of beam quality indicator for effective energy determination of continuum neutron beam"Proc. of the 2nd Japan-US Symposium on Advances in NDT. 18-23 (1999)

[Publications] J. Rant, H. Yanagie et al.: "Detection of ^<10>B distributions in histological samples by NCAR using thermal and cold neutrons and photoluminescent imaging plates"Neutron Imaging Methods to Detect Defects in Materials. 2. 687-694 (1999)

[Publications] H. Iwata, H. Kobayashi et al.: "Neutron-gamma ray radiography using a multi-color luminescent scintillator"Neutron Radiography. 6(in press). 253-260 (2000)

[Publications] H. Kobayashi et al.: "Determination of photo-stimulated luminescence signals from materials by radiation"Nucl. Instr. Method, B. (in press). (2000)

[Publications] H. Kobayashi: "Image quality : Signals and Information (Invited Lecture)"Neutron Imaging Methods to Detect Defects in Materials. 2. 687-694 (1999)

[Publications] H. Kobayashi: "Image Quality : Signal Information [Series of Lecture Neutron Radiography : States of the Art and Future Neutron radiography]"Neutron Radiography. 6(in press). 11-22 (2000)

[Publications] H. Kobayashi: "Beam formation and characterization for neutron radiography"Neutron Radiography. 6(in press). 169-176 (2000)

[Publications] H. Kobayashi: "Study for ETM cross section measurements"Neutron Radiography. 6(in press). 203-210 (2000)

[Publications] H. Kobayashi: "Basics of imaging plate for radiograms"Neutron Radiography. 6(in press). 271-278 (2000)

[Publications] K. Ono et al.: "The Combined Effect of Boronphenylalanine and Borocaptate in Boron Neutron Capture Therapy for SCCVII Tumors in Mice"Int. J. Radiat. Oncol. Biol. Phys.. 43. 431-436 (1999)

[Publications] S. Masunaga, K. Ono. et al.: "Reoxygenation in quescent and total intratumors cells following thermal neutron irradiation with or without ^<10>B compound-compared with that after γ-ray irradiation"Int. J. Radiat. Oncol. Biol. Phys.. 44. 391-398 (1999)

[Publications] 小林久夫: "ラジオグラフィー用検出器の動向とイメージングプレートの発展"放射線と産業. 88. 13-16 (1999)

[Publications] 小林久夫: "中性子イメージングにおけるIPの諸特性"放射線. 25. 53-68 (1999)

[Publications] 小林久夫: "中性子検出用イメージングプレートの特性"放射線. 25. 61-64 (1999)

柳衛宏宣東京大学, 医科学研究所, 助手 (30212278)