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1994 Fiscal Year Final Research Report Summary

Development of new-type radiommunoassay system with higher sensitivity and lower radioactive waste disposal.

Research Project

Project/Area Number 04557049
Research Category

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

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

FUJIBAYASHI Yasuhisa  Kyoto University, Department of Genetic Biochemistty, Associate Professor, 薬学部, 助教授 (50165411)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Junichi  Nihon-Medi-physics, Co.Ltd., Research and Development Center, Director., 研究開発本部, 研究部長
SAKAHARA Harumi  Kyoto University, Faculty of Medicine, Department of Nuclear Medicine, Lecturer, 医学部, 講師 (10187031)
HORIUCHI Kazuko (スズキ カズコ)  Kyoto university, Faculty of Pharmaceutical Sciences, Department of Radiopharmac, 薬学部, 助手 (50144382)
Project Period (FY) 1992 – 1994
Keywordsradioimmunoassay / high specific activity / metal label / gallium / Indium / antisense oligonucleotide / antibody / digoxin
Research Abstract

To achieve higher sensitivity in the detection of biologically active substances (ca..antibodies, drugs, antisense oligonucleotides, etc.) and lessen radioactive waste disposal, short-lived gamma emitting metal radionuclide was attached to such molecules. Gallium-67(Ga-67, half life=78hr)or indium-111 (In-111, half life=2.8day) was selected as a metalradionuclide and biologically active substances conjugated with deferoxamine, diethylenetriamine-pentaacetic acid or isothiocyanobenzyl-EDTA were radiolabeled.
(1) Antibody : monoclonal anti-human growth hormone (GH) antibody was conjugated with deferoxiamine (DF) through dialdehyde-starch polymer spacer and labeled with Ga-67. Using this Ga-67-anti-GH antibody, immunoradiometric assay with 10 times higher sensitivity could be realized.
(2) Drug : digoxin, a cardiac glycoside requireing therapeutic drug monitoring, was labeled with Ga-67 using DF as a bifunctional chelating agent. Ga-67-DF-digoxin has similar affinity to anti-digoxin antibody as well as Na, K-ATPase. Using the Ga-67-DF-digoxin, digoxin-RIA as well as myocardial Na, K-ATPase imaging in vivo.were successfully performed.
3) Antisense oligonucleotide : Antisense oligonucleotide against human c-erbB-2 was 5'-aminated and conjugated with isothiocyanobenzyl-EDTA (IBE) and labeled with In-111. In-111-IBE-oligonucleotide showed high stability even in human serum, an indication of possible in-vivo application. In fact, biodistribution study in nude mice bearing c-erbB2 mRNA (+) tumor indicated the sequence selective tumor localization.
It was concluded that short-lived metal radionuclide can be used not only for in vivo nuclear medicine, but in vitro diagnosis as well as basic research studies.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Y. Takemura, Y. Fujibayashi, et al.: "Development of glycoside-bound radiopharmaceuticals: novel radioiodination method for digoxin." Biological & Pharmaceutical Bulletin. 17. 97-101 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Okazawa, Y. Yonekura, Y. Fujibayashi, et al.: "Clinical application and quantitative evaluation of generator-produced copper-62-labeled PTSM as a brain perfusion tracer for PET." Journal of Nuclear Medicine. 35. 1910-1915 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Fujibayashi, H. Taniuchi, et al.: "Differential retention mechanism of Cu-pyruvaldehyde bis (N4-methylthiosemicarbazone) (Cu-PTSM) by brain and tumor. A novel radiopharmaceutical for positron emission tomography imaging." Annals of Nuclear. Medicine. ( in press ). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takemura, Y.Fujibayashi, et al: "Development of glycoside-bound radiopharmaceuticals : novel radioiodination method for digoxin." Biological & Pharmaceutical Bulletin. 17. 97-101 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Okazawa, Y.Yonekura, Y.Fujibayashi, et al: "Clinical application and quantitative evaluation of generator produced copper-62-labeled PTSM as a brain perfusion tracer for PET" Journal of Nuclear Medicine. 35 (12). 1910-1915 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Fujibayashi, H.Taniuchi, et al.: "Dfferential retention mechanism of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM) by brain and tumor. A nobel radiopharmaceutical for positron emission tomography imaigng" Annals of Nuclear Medicine. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15   Modified: 2021-09-30  

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