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Development of isoform-specific amino acid transporter imaging agent

Research Project

Project/Area Number 17390336
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionIbaraki Prefectural University of Health Science

Principal Investigator

SHIKANO Naoto  Ibaraki Prefectural University of Health Science, Department of Radiological Sciences, Assistant Professor (80295435)

Co-Investigator(Kenkyū-buntansha) SHIKAWA Nobuyoshi  Ibaraki Prefectural University of Health Sciences, Department of Radiological Sciences, Professor (10026932)
KAWAI Keiichi  Kanazawa University, Faculty of Medicine, Professor (30204663)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥8,940,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordsradiopharamaceutical / artificial amino acid / L-type amino acid transporter / 4F2hc / neutral amino acid / functional imaging / system L / isoform selectivity / 放射性医薬品 / 人工アミノ酸 / アミノ酸輸送 / 機能診断薬 / 画像診断薬 / L系 / アイソフォーム選択性
Research Abstract

Human L-type amino acid transporter 1 (hLAT1), a component of system L, is expressed in a wide variety of organs. Its highest expression levels are in the brain, placenta, testis, bone marrow and fetal liver, followed by peripheral leukocytes, lymph nodes and the thymus. In a previous study, LAT1 was found to act as a system L transporter at the blood-brain barrier and tumor tissue. On the other hand, hLAT2, an isoform of hLATi, involves in the trans-cellular transport of neutral amino acids in epithelia blood-tissue barriers. Development of isoform-specific amino acid transporter agent is helpful about clarification of amino acid metabolic disease. We examined system-selectivity of 3-[^ (125) I]iodo-α-methyl-L-tyrosine (^<125>IMT), 4-[^<125>I]iodo-L-meta-tyrosine (4-[^<125>I]-mTyr) and 3-[^<125>I]iodo-L-tyrosine (3-[^<125>I]-Tyr) transport in Chinese hamster ovary cell K1 (CHO-K1) and those isoform-selectivity of the two human L-type amino acid transporters, hLAT1 and hLAT2 with human 4F2hc co-expressed Xenopus laevis oocytes. CHO-Klcell line studies have revealed that 4-[^<125>I]-mTyr exhibited the greatest system L specificity (93.46±0.13%) of all the amino acids tested, and therefore shows promise as a system-L-selective amino acid transport marker. [^<125>I]IMT, 4-[^<125>I]-mTyr and 3- [^<125>I] -Tyr transport was hLAT1-selective. Animal studies with these compounds are anticipated in further studies.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (20 results)

All 2007 2006

All Journal Article (15 results) (of which Peer Reviewed: 6 results) Presentation (5 results)

  • [Journal Article] Transport of D-[1-^<14>C]-amino acids into Chinese hamster ovary cells (CHO-K1):implications for use of labeled D-amino acids as molecular imaging agents2007

    • Author(s)
      N.Shikano, et. al.
    • Journal Title

      Nucl Med Biol 34

      Pages: 659-665

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of 3-[_<125>I]iodo-alpha-methyl-L-tyrosine,a tumor imaging agent,after probenecid loading in mice implanted with colon cancer DLD-1 cells2007

    • Author(s)
      S.Nakajima, et. al.
    • Journal Title

      Nucl Med Biol 34

      Pages: 1003-1008

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Transport of D-[1-^<14>C]-amino acids into Chinese hamster ovary cells (CHO-K1) : implications for use of labeled D-amino acids as molecular imaging agents2007

    • Author(s)
      N. Shikano. S. Nakajima, T. Kotani, M. Ogura, J. Sagara, Y. Iwamura, M. Yoshimoto, N. Kubota, N. Ishikawa, K. Kawai
    • Journal Title

      Nucl Med Biol 34

      Pages: 659-665

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pharmacokinetics of 3-[^<125>I]iodo-alpha-methyl-L-tyrosine, a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells2007

    • Author(s)
      S. Nakajima, N. Shikano, T. Kotani, M. Ogura, R. Nishii, M. Yoshimoto, N. Yamaguchi, Y. Iwamura, N. Kubota, N. Ishikawa, K. Kawai
    • Journal Title

      Nucl Med Biol 34

      Pages: 1003-1008

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Recent advance in molecular pharmacological studies on radioiodinated 3-iodo-alpha-methyl-L-tyrosine, an L-type amino acid transporter 1-selective tumor imaging agent for SPECT2007

    • Author(s)
      N. Shikano
    • Journal Title

      ASVPI 12

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fluorescent X-ray imaging with synchrotron radiation for the evaluation of probes for biomedical functions : A pilot study on 4-bromo-DL-phenylalanine for cancer detection in mice2007

    • Author(s)
      N. Shikano, T. Kotani, S. Nakajima, M. Ogura, K. Hyodo, H. Sugiyama, M. Monma, K. Kawai, T. Takeda, N. Kubota, K. Nishimura, K. Mori, N. Ishikawa
    • Journal Title

      ASVPI 12

      Pages: 67-73

    • NAID

      110006427212

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transport of D-[1-14C]-amino acids into Chinese hamster ovary cells (CHO-K1): implications for use of labeled D-amino acids as molecular imaging agents.2007

    • Author(s)
      N. Shikano, et. al.
    • Journal Title

      Nucl Med Biol 34

      Pages: 659-665

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of 3-[125I]iodo-alpha-methyl-L-tyrosine, a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells.2007

    • Author(s)
      S. Nakajima, et. al.
    • Journal Title

      Nucl Med Biol 34

      Pages: 1003-1008

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescent X-ray imaging with synchrotron radiation for the evaluation of probes for biomedical functions: A pilot study on 4-bromo-DL-phenylalanine for cancer detection in mice.2007

    • Author(s)
      N. Shikano, et. al.
    • Journal Title

      茨城県立医療大学紀要 12

      Pages: 67-73

    • NAID

      110006427212

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of maleate-induced Fanconi syndrome by decreasing {accumulation of ^<125>I-3-iodo-α-methyl-L-trosine in the proximal tuule segment-1 region of renal cortex in mice: atrial of separate evaluation of reabsorption2006

    • Author(s)
      Shikano N, et. al.
    • Journal Title

      Ann Nucl Med 20

      Pages: 175-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Detection of maleate-induced Fanconi syndrome by decreasing accumulation of ^<125>I-3-iodo-a-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice : a trial of separate evaluation of reabsorption2006

    • Author(s)
      N. Shikano, S. Nakajima, T. Kotani, Y. Itoh, R. Nishii, M. Yoshimoto, L.G. Flores 2nd, H. Saji, N. Ishikawa, K. Kawai
    • Journal Title

      Ann Nucl Med 20

      Pages: 175-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Presence of murine intracisternal A particle-like sequences in various animal species2006

    • Author(s)
      A. Okada, N. Shikano, M. Ohtake, Y. Iwamura
    • Journal Title

      ASVPI 11

      Pages: 65-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Detection of maleate-induced Fanconi syndrome by decreasing accumulation of ^<125>I-3-iodo-α-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice : a trial of separate evaluation of reabsorption.2006

    • Author(s)
      Shikano N et al.
    • Journal Title

      Ann Nucl Med 20

      Pages: 175-181

    • NAID

      10018776138

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Presence of murine intracisternqal A particle like sequences in various animal species2006

    • Author(s)
      Okada A, Shikano N, Ohtake M, Iwamura Y
    • Journal Title

      ASVPI 11

      Pages: 65-70

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Detection of maleate-induced Fanconi syndrome by decreasing accumulation of ^<125>I-3-iodo-α-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice : a trial of separate evaluation of reabsorption.2006

    • Author(s)
      Shikano N et al.
    • Journal Title

      Ann Nucl Med 20・2(In press)

    • NAID

      10018776138

    • Related Report
      2005 Annual Research Report
  • [Presentation] Assessment of D-[1-^<14>C]-amino acids transport using Chinese hamster ovary cells : implications for use of labeled D-amino acids as molecular imaging agents2007

    • Author(s)
      N. Shikano, N. Nakajima, T. Kotani, M. Ogura, R. Nishii, K. Nishi, M. Yoshimoto, N. Kubota, N. Ishikawa, K. Kawai
    • Organizer
      Joint Molecular Imaging Conference
    • Place of Presentation
      Providence, Rhode Island USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Enzymatic activity of the 392 bp fragment from deleted mitochondrial CAN sequence2007

    • Author(s)
      K. Iwai, T. Baba, N. Shikano, S. Nakajima, M. Miyake, N.D. Parry, Y. Sakisaka, Y. Iwamura
    • Organizer
      Biochemistry and Molecular Biology 2007
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Assessment of D-[1-14C]-amino acids transport using Chinese hamster ovary cells: implications for use of labeled D-amino acids as molecular imaging agents.2007

    • Author(s)
      N. Shikano, et. al.
    • Organizer
      Joint Molecular Imaging Conference
    • Place of Presentation
      Rhode Island USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Transport selectivity of 3-[^<123>I]iodo-alpha-methyl-L-tyrosine in human L-tupe amino acid transnorters2006

    • Author(s)
      Shikano N, et. al.
    • Organizer
      9th Congress of the World Federation of Nuclear Medicine and Biology
    • Place of Presentation
      Seoul,Korea
    • Year and Date
      2006-10-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Membrane transport of radioiodinated 3-iodo-alpha-methyl-L-tyrosine in Chinese hamster ovary cell2006

    • Author(s)
      N. Shikano, A. Okada, S. Nakajima, T. Kotani, M. Ogura, N. Kubota, N. Ishikawa, Y. Iwamura
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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