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Development of ^<99m>Tc-complexes for imaging cancer metastasis

Research Project

Project/Area Number 09672190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKumamoto University

Principal Investigator

NAKAYAMA Morio  Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60164373)

Co-Investigator(Kenkyū-buntansha) HARADA Kumiko  Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (70150547)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsHydroxamic acid / Cancer / ^<99m>Tc / ヒドロキサムアミド / ^<99m>Tc錯体
Research Abstract

We planed to develope the imaging agent for cancer metastasis by the two approaches as followes :
(1) Production of ^<99m>Tc-labded compounds by the introduction of ^<99m>Tc-complexes to the antibody or polypeptide that shows high affinity for the antigen or receptor on cell membrane of primary canncer and the important
factor for angiogenesis
(2) Development of ^<99m>Tc-coinplexes that show high affinity for tumor.
Since ^<99m>Tc-iagnostic agents essetially contains the ^<99m>Tc by the coordinate bond, the behavior of ^<99m>Tc in vivo is very influenced by the equilibrium state involving the ligand and ^<99m>Tc. Accordingly, the present ^<99m>Tc-radiopharmaceuticals have developed on the base of the strategy described above (1), namely many researchers developed the various ligand systems that form the higly stable ^<99m>Tc-complexes. However, the ligand system availabe for the clinical use has not been completed.
On the other hand, though it is known that seine polynucleus metal complexes show high affinity for tumor, the systematic research has never been carried out.
In this study, We selected the two ligand systems to perform the duvelopment of ^<99m>Tc-complexes for imaging cancer metastasisboth by the two way. One is hydroxamamide ligand system which form stable ^<99m>Tc-complex. The other is hydroxamica acid ligand system which have the possibility for the formation of the polynucleous ^<99m>Tc-complexes. The difference in ligand system resulted in the change of the properties of ^<99m>Tc-complex and the behavior of ^<99m>Tc in vivo.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 中山 守雄: "Hydroxamamide as a chelating moiety for the preparation of ^<99m>Tc-radiopharmaceuticals III Characterization of 99mTc-hydroxamamides." Appl.Rad,Isotop.48巻. 571-577 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 許 楽村: "Synthesis and evaluation of hydroxamamide-based tetradentate ligands as a new class of thiol free chelating molecules for ^<99m>Tc radiopharmaceuticals." Nucl.Med.Biol.25巻. 295-303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 荒野 泰: "Assessment of the radiochemical design of antibodies with a metabolizable linkage for target-selective radioactivity delivery." Bioconjugate Chem.9巻. 497-506 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 許 楽村: "Bis(Hydroxamamide)-Based Bifunctional Chelating Agent for ^<99m>Tc Labeling of Polypeptides and Peptides." Bioconjugate Chem.10巻. 9-17 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 荒野 泰: "Chemical design of radiolabeled antibody fragments for low renal radioactivity levels" Cancer Res.59巻. 128-134 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小野 正博: "Intracellular Metabolic Fate of Radioactivity after Injection of ^<99III>Tc-Labeled Hydrazino Nicotinamide Derivatized Polypeptides." Bioconjugate Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama M: "Hydroxamamide as a chelating moiety for the preparation of ^<99m>Tc-radiopharmaceuticals III.Characterization of ^<99m>Tc-hydroxamamides." Appl.Rad, Isotop.48. 571-577 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakisaka K.: "A novel radioiodination reagent for protein radiopharmaceuticals with L-lysine as a plasma-stable metabolizable linkage to liberate m-iodohippuric acid after lysosomal proteolysis." J.Med.Chem.40. 2643-2652 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Xu LC: "Synthesis and evaluation of hydroxamamide-based tetradentate ligands as a new class of thiol free chelating molecules for ^<99m>Tc radiopharmaceuticals." Nucl.Med.Biol.25. 295-303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arano Y: "Assessment of the radiochemical design of antibodies with a metabolizable linkage for target-selective radioactivity delivery." Bioconjugate Chem.9. 497-506 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Xu LC: "Bis (Hydroxamamide) -Based Bifunctional Chelatin Agent for ^<99m>Tc Labeling of Polypeptides and Peptides." Bioconjugate Chem.10. 9-17 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arano Y: "Chemical design of radiolabeled antibody fragments for low renal radioactivity levels 1." Cancer Res.59. 128-134 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono M: "Intracellular Metabolic Fate of Radioactivity after Injection of ^<99m>Tc-Labeled Hydrazino Nicotinamide Derivatized Polypeptides." Bioconjugate Chem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 許 楽村: "Synthesis and evaluation of hydroxamamide-based tetradentate ligands as a new class of thiol free chelating molecules for ^<99m>Tc radiopharmaceuticals." Nucl.Med.Biol.25巻. 295-303 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 許 楽村: "Bis(Hydroxamamide)-Based Bifunctional Chelating Agent for^<99m>Tc Labeling of Polypeptides and Peptides." Bioconjugate Chem.10巻. 9-17 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 荒野 泰: "Chemical design of radiolabeled antibody fragments for low renal radioactivity levels" Cancer Res.59巻. 128-134 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中山 守雄: "Hydroxamamide as a Chelating Moiety for the Preparation of ^<99m>Tc-radiopharmaceuticals." Appl. Radiat. Isot.48巻・5号. 571-577 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 許 楽村: "Synthesis and Evaluation of Hydroxamamide-Based Tetradentate Ligands as a New Class of Thiol-Free Chelating Molecules for ^<99m>Tc-radiopharmaceuticals." Nuclear Medicine & Biology. 25巻(発表予定). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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