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Development of tumor-seeking compounds for neutron capture therapy by clarification of the accumulating mechanism

Research Project

Project/Area Number 10680486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Nuclear engineering
Research InstitutionShinshu University

Principal Investigator

YOSHIRO Kazuo  faculty of Science, Shinshu University, Associate Professor, 理学部, 助教授 (70143964)

Co-Investigator(Kenkyū-buntansha) HIRATSUKA Junichi  Kawasaki University School of Medicine Associate Professor, 助教授 (30192298)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsBoron Neutron Capture Therapy (BNCT) / ィイD111ィエD1B-NMR / melanoma / p-Boronophenylalanine / melanin / p-Boronophenylalanine-tyrosine dipeptide / 中性子捕捉療法(BNCT) / ^<11>B-NMR / p-ボロノフェニルアラニン / p-ボロノフェニルアラニン チロシン ジペプチド / 中性子捕捉療法 / 腫瘍集積性化合物 / 悪性黒色腫
Research Abstract

Boron neutron capture therapy (BNCT) is a following therapy. After accumulation of ィイD110ィエD1B in cancer tissues and then neutrons are irradiated, and using produced neutron fission energy cancer parts are destroyed. BNCT was applied to the malignant melanoma using p-Boronophenylalanine (BPA), and good results have been obtained. In order to increase the effects, a further ィイD110ィエD1B accumulation is expected. For such a purpose, it is important that after clarification of the accumulation mechanism, and based on the results, new compounds with tumor accumulation property are synthesized. In this purpose of the study it is important to develop compounds with more strong selective property by the investigation the relation between melanoma-related materials and BPA using ィイD111ィエD1B-NMR and elucidation the ィイD110ィエD1B accumulation property. JEOL LA400 NB of Shinshu University was used. The ィイD111ィエD1B concentration in the sample was very low, then a large numbers of accumulation was req … More uired. As a result, the obtained spectra has large curved background, and it is impossible to detect the peak of complex which is due to the relation between the melanin related materials and BPA. In 1998, we have tried to improve the curved background by subtracting the signal of the water containing solution from that of the samples. Using this method. The interaction was investigated between the melanoma-related materials which was taken out melanoma-bearing hamsters and BPA. As a result, the ィイD111ィエD1B-NMR peak of BPA decreases with time, and that of boric acid, which is considered to be formed -after BPA interacted with melanoma-related materials, increases. This is indirect confirmation of the interaction between BPA and melanoma-related materials. In 1999, we have synthesized BPA-tyrosine dipeptide. Tyrosine is a melanin precursor. In melanoma, melanin synthesis is accentuated, and uptake of tyrosine increases. Therefore, BPA-tyrosine dipeptide is expected to be much more incorporated into melanoma than BPA. Since BPA and tyrosine are amino acid and both can exist either L-form or D-form, then we have tried to synthesize four optical isomers, L-BPA-L-tyrosine, L-BPA-D-tyrosine, D-BPA-L-tyrosine, and D-BPA-D-tyrosine. Less

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 吉野和夫他: "10B-ρ-ボロノフェニルアラニンによる10Bのメラノーマ細胞への取り組みとその集積機構"Bkin Cancer. 13・1. 8-11 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Fukuda, K.Yoshino: "Phamacokinetics of 10B-ρ-borono-phenylalanine in tumors, skin and blood of melanoma patients : a study of boron neutron capture therapy for malignant melanoma"Melanoma Research. 9. 75-83 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Saitake, K.Yoshino: "Synthesis of ρ-boronophenyl-alanine(p-BPA)-tyrosine dipeptide"Peptide Science 1998. 289-292 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ki Chul Park, K. Yoshino: "A high-yield synthesis of 4-borono-DL-phneylalanine"Synthesis. 12. 2041-2044 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J.Hiratsuka, K.Yoshino: "Selective Uptake of ρ-and m-Boronophenylalanine increases by Transfecting Tyrosinase Gene to Melanoma Cells"Melanoma Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Yoshino, Y.Tanaka: "Simultaneous Determination of ρ-Boronophenylalanine and Boric acid Using 11B-NMR"Frontiers in Neutron Capture Therapy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉野和夫他: "^<10>B-p-ボロノフェニルアラニンによる^<10>Bのメラノーマ細胞への取り込みとその集積機構"Skin Cancer. 13・1. 8-11 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Fukuda,K.Yoshino: "Phamakokinetics of ^<10>B-p-boronophenylalanine in tumors. skin and blood of melanoma patients: 以下略"Melanoma Reseach. 9. 75-83 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Saitake,K.Yoshino他: "Synthesis of p-boronophenylalanine (p-BPA)-tyrosine peptide"Peptide Science 1998. 289-292 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ki Chul Park,K.Yoshino他: "A high-yield synthesis of 4-borono-DL-phenylalanine"Synthesis. 12. 2041-2044 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] J.Hiratsuka,K.Yopshino他: "Selective uptake of p-boronophonylalanine increases by mansfeaing the tyrosinase geno into amelanotic melanoma"Melanoma Reseach. In press.

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Yoshino,Y,Tanaka他: "Simaltaneous determination of p-boronophenylalanine and poricacid sing ^<11>B-NMR"Frontiers in Neuiron Capture Therapy. In press.

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉野 和夫: "^<10>B-p-ボロノフェニルアラニンによる^<10>Bのメラノーマ細胞への取り込みとその集積機構" Skin Cancer. 8-11 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 稲本 美郎: "ホウ素を含むアミノ酸誘導体のフッ素化" Kyoto University Research Reactor Institute-KR. 26. 52-55 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上條 まみこ: "p-ボロノフェニルアラニンとメラニンポリマー生成との関連(in vivo)" Kyoto University Research Reactor Institute-KR. 26. 56-62 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 北沢 美幸: "p-BPA-フルクトース錆体の^<13>C-NMRによる‘Jccカップリング定数を用いた構造決定" Kyoto University Research Reactor Institute-KR. 26. 63-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 北沢 美幸: "ホウ酸基を持つチロシン誘導体の合成の試み" Kyoto University Research Reactor Institute-KR. 26. 68-74 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉野 和夫: "^<11>B-NMRによる微量ホウ素の定量" Kyoto Universitiy Research Reactor Institute-KR. 26. 75-79 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 才竹 芳寛: "p-ボロノフェニルアラニンとチロシンのジペプチドの合成" Kyoto University Research Reactor Institute-KR. 26. 80-83 (1998)

    • Related Report
      1998 Annual Research Report

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

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