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Drug discovery research for SPECT imaging of cell-cell comunication in in vivo

Research Project

Project/Area Number 16K10277
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionOsaka University

Principal Investigator

Shirakami Yoshifumi  大阪大学, 医学系研究科, 特任准教授(常勤) (00560400)

Co-Investigator(Kenkyū-buntansha) 池田 隼人  東北大学, サイクロトロン・ラジオアイソトープセンター, 助教 (30649083)
畑澤 順  大阪大学, 医学系研究科, 教授 (70198745)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルファ線 / 核医学治療 / 内容療法 / アミノ酸 / すい臓がん / グリオーマ / 甲状腺がん / アスタチン / 内用療法 / ギャップ結合 / 心不全 / SPECT診断 / アルファ線内用療法 / 核医学 / 放射性医薬品 / ペプチド / 123I / SPECT / 211At / コネキシン43 / PET / ギャップ結合チャネル
Outline of Final Research Achievements

We have developed a few new durgs coupled with an alpha particle emitting radioactive nuclide, astatine-211(211At), which are useful for tumor treatment. Small molecules can be labelled with 211At by a boron-astatine electrophilic replacement reaction. Three patents were filed. Tumor lesions of mice xenografted with brain tumor, pancreatic tumorand thyroid cancer were significantly reduced after a single injection of amino acid analog labelled with 211At. 211At is convvenient not only for treatment but also for imaging (=Radiotheranostics). Currently non-clinical studies including pharmacodynamics and toxicological studies are ongoing. We are expecting to conduct physician sponsored clinical studies in 2 years.

Academic Significance and Societal Importance of the Research Achievements

今日のがん治療は著しく進歩しているが、未だに脳腫瘍やすい臓がんの5年生存率は極めて低く(10%未満)、既存のいかなる治療法によっても治療が困難ながんである。甲状腺がんのように5年生存率が高い場合でも(>90%)、まったく治療法のない難治性型の患者さんも一定数いる。我々の開発した新しいがん治療法、α線核医学治療は、アスタチン-211を分子標的化合物に標識することにより、患部をα線で狙い撃ちする(一気にたたく)新しいコンセプトを提供するものである。化学療法ではどんなに優れた薬剤でも耐性の発現や遺伝子変異が避けられない問題となるが、α線核医学治療ではそれらの影響をほとんど無視できる点が有利である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (2 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 3 results)

  • [Journal Article] Enhancement of astatine-211 uptake via the sodium iodide symporter by the addition of ascorbic acid in targeted alpha therapy of thyroid cancer2019

    • Author(s)
      Watabe Tadashi、Kaneda-Nakashima Kazuko、Liu Yuwei、Shirakami Yoshifumi、Ooe Kazuhiro、Toyoshima Atsushi、Shimosegawa Eku、Fukuda Mitsuhiro、Shinohara Atsushi、Hatazawa Jun
    • Journal Title

      Journal of Nuclear Medicine

      Volume: - Issue: 9 Pages: 1-43

    • DOI

      10.2967/jnumed.118.222638

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Preparation of aqueous solution of 211At-sodium astatide (Na211At) in a high radiochemical purity and its biodistribution study in rats2018

    • Author(s)
      Shirakami Y, Kaneda K, Watabe T, Liu Y, Shimosegawa E, Shinohara A, Hatazawa J.
    • Organizer
      World J Nucl Med
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancement of At-211 uptake in the thyroid gland: SPECT study in rats2018

    • Author(s)
      Liu Y, Watabe T, Kaneda-Nakashima K, Shirakami Y, Toyoshima A, Tatsumi M, Shimosegawa E, Fukuda M, Shinohara A, Hatazawa J
    • Organizer
      Jpn Soc Mol Imag
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アスタチン(211At)の酸化還元反応とα線治療薬の創薬研究2018

    • Author(s)
      白神宜史, 兼田加珠子, 渡部直史, Victor Romanov, 張子見, 大江一弘, Yuwei Liu, 下瀬川恵久, 篠原厚, 畑澤順
    • Organizer
      第2回日本核医学会分科会放射薬品科学研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Radiolabeling of small molecules with astatine (211At) for theranostics2018

    • Author(s)
      Y Shirakami
    • Organizer
      BER2018
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Preparation of aqueous solution of 211At-sodium astatide (Na211At) in high radiochemical purity and its biological properties in rats2018

    • Author(s)
      Yoshifumi Shirakami, Kazuko Kaneda-Nakashima, Tadashi Watabe, Yuwei LiuAtsushi Toyoshima, Eku Shimosegawa, Atsushi Shinohara, Jun Hatazawa
    • Organizer
      WFNMB2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A new method for the preparation of astatine-211(211At) and iodine-123(123I) labelled amino acid analogues of phenylalanine, 211At-Phe and 123I-Phe, for radionuclide therapy and SPECT imaging applications2017

    • Author(s)
      Y Shirakami, H Ikeda, J Hatazawa
    • Organizer
      EANM2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 産学共創プラットフォーム共同研究推進プログラムOPERA QiSS

    • URL

      https://www.rcnp.osaka-u.ac.jp/~qiss/

    • Related Report
      2018 Annual Research Report
  • [Remarks] http://www.rcnp.osaka-u.ac.jp/~qiss/

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 211At標識アミノ酸誘導体を含む医薬組成物及びその製造方法2019

    • Inventor(s)
      深瀬浩一, 篠原厚,金井好克, 白神宜史, 他
    • Industrial Property Rights Holder
      大阪大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 放射標識されたアリール化合物の製造方法2018

    • Inventor(s)
      白神宜史、渡部直史、兼田加珠子、池田隼人、金井泰和、他
    • Industrial Property Rights Holder
      大阪大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アスタチン溶液及びその製造方法2018

    • Inventor(s)
      白神宜史、渡部直史、兼田加珠子、篠原厚、下瀬川恵久、畑澤順
    • Industrial Property Rights Holder
      大阪大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 放射標識されたアリール化合物の製造方法2017

    • Inventor(s)
      白神宜史、池田隼人、金井泰和、下瀬川恵久、畑澤順
    • Industrial Property Rights Holder
      白神宜史、池田隼人、金井泰和、下瀬川恵久、畑澤順
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-151632
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] アスタチン溶液及びその製造方法2017

    • Inventor(s)
      白神宜史、渡部直史、兼田加珠子、下瀬川恵久、篠原厚、畑澤順
    • Industrial Property Rights Holder
      白神宜史、渡部直史、兼田加珠子、下瀬川恵久、篠原厚、畑澤順
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-255109
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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