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Development of integrin targeting liposome for imaging and radionuclide therapy of pancreatic cancer

Research Project

Project/Area Number 24591828
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Cancer Center Japan

Principal Investigator

YOSHIMOTO MITSUYOSHI  独立行政法人国立がん研究センター, その他部局等, 主任研究員 (00345638)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords膵がん / リポソーム / RGD / インテグリン / 膵癌 / RGDペプチド / 内照射治療
Outline of Final Research Achievements

αvβ3 integrin is overexpressed in endothelial cells and various tumor cells including pancreatic cancer. In this study, we developed RGD-modified liposomes for imaging and internal radionuclide therapy of pancreatic cancer. We successfully synthesized the RGD-modified liposomes with about 100 nm of particle size. The RGD-modified liposomes dose-dependently inhibited the binding of 125I-echistatin to PANC-1. The IC50 values were 5-67 μM as phospholipids. In contrast, RKG-modified liposome and unmodified liposome did not inhibit the binding. Biodistribution studies using the liposomes loaded with 111In indicated rapid clearance of the RGD-modified liposome from blood. Significant accumulation of radioactivity in spleen was found with increase in the amount of RGD modification (170.4-403.9% ID/g at 24 h). Unmodified liposome showed the highest tumor uptake (2.80% ID/g) at 24 h, whereas the RGD-modified liposomes showed the lower tumor uptake (1.47-2.25% ID/g).

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (24 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (16 results) (of which Invited: 4 results)

  • [Journal Article] Monitoring of gefitinib sensitivity with radioiodinated PHY based on EGFR expression2014

    • Author(s)
      Yoshimoto M, Hirata M, Kanai Y, Naka S, Nishii R, Kagawa S, Kawai K, Ohmomo Y.
    • Journal Title

      Biological & Pharmaceutical Bulletin

      Volume: 37 Pages: 355-360

    • NAID

      130003390939

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Controlled Administration of Penicillamine Reduces Radiation Exposure in Critical Organs during 64Cu-ATSM Internal Radiotherapy: A Novel Strategy for Liver Protection2014

    • Author(s)
      Yoshii Y, Matsumoto H, Yoshimoto M, Furukawa T, Morokoshi Y, Sogawa C, Zhang MR, Wakizaka H, Yoshii H, Fujibayashi Y, Saga T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 1 Pages: e86996-e86996

    • DOI

      10.1371/journal.pone.0086996

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SPECT/CT of lung nodules using 111In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model2013

    • Author(s)
      Hayakawa T, Mutoh M, Imai T, Tsuta K, Yanaka A, Fujii H, Yoshimoto M.
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 27 Issue: 7 Pages: 640-647

    • DOI

      10.1007/s12149-013-0729-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A useful EGFR-TK ligand for tumor diagnosis with SPECT: development of radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline.2013

    • Author(s)
      Hirata M, Kanai Y, Naka S, Yoshimoto M, Kagawa S, Matsumuro K, Katsuma H, Yamaguchi H, Magata Y, Ohmomo Y.
    • Journal Title

      Ann Nucl Med.

      Volume: 27 Issue: 5 Pages: 431-443

    • DOI

      10.1007/s12149-013-0703-y

    • NAID

      10031183404

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predominant contribution of L-type amino acid transporter to 4-borono-2-18F-fluoro-phenylalanine uptake in human glioblastoma cells2013

    • Author(s)
      Yoshimoto M, Kurihara H, Honda N, Kawai K, Ohe K, Fujii H, Itami J, Arai Y.
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 40 Issue: 5 Pages: 625-629

    • DOI

      10.1016/j.nucmedbio.2013.02.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Non-invasive X-ray Micro-computed Tomographic Evaluation of Indomethacin on Urethane-induced Lung Carcinogenesis in Mice2012

    • Author(s)
      Ueno T, Imaida K, Yoshimoto M, Hayakawa T, Takahashi M, Imai T, Yanaka A, Tsuta K, Komiya M, Wakabayashi K, Mutoh M.
    • Journal Title

      Anticancer Resarch

      Volume: 32 Pages: 1773-4780

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vivo SPECT Imaging with 111In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model.2012

    • Author(s)
      Yoshimoto M, Hayakawa T, Mutoh M, Imai T, Tsuda K, Kimura S, Umeda IO, Fujii H, Wakabayashi K
    • Journal Title

      J Nucl Med

      Volume: 53(5) Issue: 5 Pages: 765-771

    • DOI

      10.2967/jnumed.111.099630

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and evaluation of radioiodinated phenoxyquinazoline and benzylaminoquinazoline derivatives as new EGF receptor tyrosine kinase imaging ligands for tumor diagnosis using SPECT2012

    • Author(s)
      Hirata M, Kanai Y, Naka S, Matsumuro K, Kagawa S, Yoshimoto M, Ohmomo Y
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 26 Issue: 5 Pages: 67-76

    • DOI

      10.1007/s12149-012-0583-6

    • NAID

      10030788473

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Synthesis and characterization of RGD-modified liposomes for targeting αvβ3 integrin2014

    • Author(s)
      Mitsuyoshi Yoshimoto
    • Organizer
      11th World Federation of Nuclear Medicine and Biology
    • Place of Presentation
      カンクン(メキシコ)
    • Year and Date
      2014-08-27 – 2014-08-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] アニリノピリミジンを基本骨格とするEGFR-TKイメージング剤の合成と基礎的検討2014

    • Author(s)
      吉本 光喜,木村 禎亮,山田 耕平,平田 雅彦,大桃 善朗,国嶋 崇隆,川井 恵一,藤井 博史.
    • Organizer
      日本薬学会第134年回
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of novel EGFR-TK imaging agents based on anilinopyrimidine structure2013

    • Author(s)
      Yoshimoto M, Kimura S, Hirata M, Ohmomo Y, Kawai K, Fujii H.
    • Organizer
      The 60th Annual Meeting of the Society of Nuclear Medicine
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Controlled administration of penicillamine reduces radiation exposure to normal organs in 64Cu-ATSM internal radiotherapy2013

    • Author(s)
      Yoshshii Y, Matsumoto H, Yoshimoto M, Furukawa T, Yukie M, Sogawa C, Zhang M, Wakizaka H, Fujibayashi Y, Saga T.
    • Organizer
      The 60th Annual Meeting of the Society of Nuclear Medicine
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of EGFR-TK imaging probe: toward theranostic imaging2013

    • Author(s)
      Yoshimoto M, Hirata M, Yamaguchi H, Magata Y, Nishii R, Kawai K, Fujii H, Ohmomo Y.
    • Organizer
      The 6th China-Japan-Korea conference on Nuclear Medicine
    • Place of Presentation
      Jeju, Korea
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] HER2発現性癌のSPECTイメージングが可能な新規放射性薬剤の合成と基礎評価2013

    • Author(s)
      平田雅彦, 吉本光喜, 小川美香子, 間賀田泰寛, 大桃善朗
    • Organizer
      日本薬学会第133年回
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 分子標的薬耐性化の判定を目指した新規SPECTプローブの開発2013

    • Author(s)
      服部久範, 梅田泉, 木村禎亮, 吉本光喜, 藤井博史
    • Organizer
      日本薬学会第133年回
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 111In-DOTA-c(RGDfK)による早期膵がんイメージングとRI内用療法の可能性2013

    • Author(s)
      吉本光喜
    • Organizer
      第16回PET分子イメージングセミナー
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Development of RGD-liposomes for MR imaging of pancreatic tumor2012

    • Author(s)
      Yoshimoto M, Hayakawa T, Yamaguchi M, Kimura S, Umeda IO, Fujii H.
    • Organizer
      2012 World Molecular Imaging Congress
    • Place of Presentation
      Dublin, Ireland
    • Related Report
      2012 Research-status Report
  • [Presentation] Evaluation of radioiodinated PYK for monitoring active mutation of EGFR-TK2012

    • Author(s)
      Yoshimoto M, Hirata M, Magata Y, Nishii R, Kawai K, Ohmomo Y
    • Organizer
      The 59th Annual Meeting of the Society of Nuclear Medicine
    • Place of Presentation
      Florida, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Evaluation of 64Cu-ATSM for an internal radiotherapy agent against CD133+ cancer stem cells with human colon carcinoma: 64Cu-ATSM treatment caused cell apoptosis2012

    • Author(s)
      Yoshshii Y, Furukawa T, Kiyono Y, Yoshii H, Yoshimoto M, Fujibayashi Y, Saga T
    • Organizer
      The 59th Annual Meeting of the Society of Nuclear Medicine
    • Place of Presentation
      Florida, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] 18F-FBPAのヒト脳腫瘍細胞株への集積機序:14C-Methionineとの比較2012

    • Author(s)
      吉本光喜,栗原宏明,南間貴之,本田納紀,川井恵一,藤井博史
    • Organizer
      第52回日本核医学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] ハムスター化学発がんモデルを用いた111In-DOTA-c(RGDfK)による早期膵癌イメージング2012

    • Author(s)
      吉本 光喜,早川 拓也,武藤 倫弘,今井 俊夫,津田 啓介,木村 禎亮,梅田 泉,藤井 博史,若林 敬二
    • Organizer
      第52回日本核医学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 乳癌の特性診断を目的としたHER2標的新規キナゾリン誘導体の合成と基礎的検討2012

    • Author(s)
      平田雅彦,吉本光喜,小川美香子,間賀田泰寛,大桃善朗
    • Organizer
      第52回日本核医学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 国立がん研究センターにおける分子イメージング研究2012

    • Author(s)
      吉本光喜
    • Organizer
      金沢大学戦力的研究推進プログラム(拠点形成型)次世代重点研究プログラム学術講演会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 腫瘍診断における 分子イメージングの役割2012

    • Author(s)
      吉本光喜
    • Organizer
      日本毒性病理学会主催第13回教育セミナー
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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