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Development of a Novel Lung Tumor Marking Method Utilizing Fluorescence Spectrum Analysis Thoracoscopy and 5-ALA

Research Project

Project/Area Number 18K08774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionHokkaido University

Principal Investigator

Aragaki Masato  北海道大学, 大学病院, 講師 (30788245)

Co-Investigator(Kenkyū-buntansha) 加藤 達哉  北海道大学, 大学病院, 教授 (20624232)
海老原 裕磨  北海道大学, 大学病院, 特任教授 (50632981)
櫻井 遊  千葉大学, 大学院薬学研究院, 特任助教 (00707234)
樋田 泰浩  北海道大学, 大学病院, 准教授 (30399919)
加賀 基知三  北海道大学, 大学病院, 講師 (80224335)
Project Period (FY) 2022-01-04 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胸腔鏡手術 / 肺がん / 光線力学的治療 / Photosesityzer / 内視鏡 / PDT / レーザー / アブスコパル効果 / 5-ALA / マウスxenograftモデル / photosensityzer / rabbit orthotopic model / 蛍光イメージング / 術中マーキング
Outline of Research at the Start

肺腫瘍性病変に対する胸腔鏡手術のための新たなマーキング法の開発を目的とする。現在の肺腫瘍マーキング法の欠点は、①腫瘍自体をマーキングすることができない、②肺表面から離れた深部の病変を同定できない、③透視やCTを使用する方法はX線被爆がある、④気胸や空気塞栓といった重篤な合併症を来すことが挙げられる。われわれは共同研究者により開発された蛍光スペクトル測定装置を付加した内視鏡システムと新しい光増感剤を使用した新たな深部肺腫瘍マーキング法の開発とそれを利用した肺癌のPDT治療をにつなげるための基礎的実験が本研究の概要である。

Outline of Final Research Achievements

This study aimed to develop a new marking method for thoracoscopic surgery targeting lung tumors. We used 5-ALA, porphyrin-based porphyrin lipoprotein (PLP), Porphysome, and OTL38. While 5-ALA proved difficult for marking lung tumors due to its short excitation light, other photosensitizers showed potential applicability. The efficacy of these methods was tested using mouse and porcine pseudo-tumor models, and the potential for clinical application was discussed. Additionally, we presented basic data on sentinel lymph node mapping for lung cancer using ICG. The application of photosensitizers in lung cancer surgery and treatment extends to tumor identification and photodynamic therapy (PDT). Specifically, we found that PLP-based PDT exhibited high anti-tumor effects and induced an abscopal effect, and these findings were published.

Academic Significance and Societal Importance of the Research Achievements

胸腔鏡手術は、術後の早期回復、除痛効果、美容上の利点など、多くの利点を持つ低侵襲手術であり、機能温存による術後患者のQOL向上にもつながる。精度の高い腫瘍局在診断法が確立すれば、低侵襲手術の確立、機能温存、手術時間の短縮、術後在院日数の短縮、術後障害の軽減によるQOLの向上、そして確実な腫瘍の切除が期待できる。また、PDTが肺癌治療の選択肢の一つとなれば、低侵襲な治療としてその意義は大きい。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2018 Annual Research Report
  • Research Products

    (16 results)

All 2024 2023 2022 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (6 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Int'l Joint Research] トロント大学(カナダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] トロント大学(カナダ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] トロント総合病院胸部外科/トロント大学医学生物物理学教室(カナダ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Imaging Microbubbles With Contrast-Enhanced Endobronchial Ultrasound2024

    • Author(s)
      McGrath Sean、Shen Yu-Jack、Aragaki Masato、Motooka Yamato、Koga Takamasa、Gregor Alexander、Bernards Nicholas、Cherin Emmanuel、Demore Christine E.M.、Yasufuku Kazuhiro、Matsuura Naomi
    • Journal Title

      Ultrasound in Medicine and Biology

      Volume: 50 Issue: 1 Pages: 28-38

    • DOI

      10.1016/j.ultrasmedbio.2023.08.020

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection2023

    • Author(s)
      Sata Yuki、Aragaki Masato、Inage Terunaga、Bernards Nicholas、Gregor Alexander、Kitazawa Shinsuke、Yokote Fumi、Koga Takamasa、Ogawa Hiroyuki、Hiraishi Yoshihisa、Ishiwata Tsukasa、Effat Andrew、Kazlovich Kate、Chan Harley、Yoshino Ichiro、Yasufuku Kazuhiro
    • Journal Title

      JTCVS Techniques

      Volume: 22 Pages: 292-304

    • DOI

      10.1016/j.xjtc.2023.09.005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Optimization of thrombolytic dose for treatment of pulmonary emboli using endobronchial ultrasound-guided transbronchial needle injection2023

    • Author(s)
      Aragaki Masato、Inage Terunaga、Ishiwata Tsukasa、Gregor Alexander、Bernards Nicholas、Kato Tatsuya、Yasufuku Kazuhiro
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: 165 Issue: 5 Pages: e210-e221

    • DOI

      10.1016/j.jtcvs.2022.08.044

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.2023

    • Author(s)
      Lou J, Aragaki M, Bernards N, Chee T, Gregor A, Hiraishi Y, Ishiwata T, Leung C, Ding L, Kitazawa S, Koga T, Sata Y, Ogawa H, Chen J, Kato T, Yasufuku K, Zheng G.
    • Journal Title

      Biomaterials.

      Volume: 292 Pages: 121918-121918

    • DOI

      10.1016/j.biomaterials.2022.121918

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping2023

    • Author(s)
      Gregor Alexander、Sata Yuki、Hiraishi Yoshihisa、Ishiwata Tsukasa、Aragaki Masato、Kitazawa Shinsuke、Koga Takamasa、Ogawa Hiroyuki、Bernards Nicholas、Yasufuku Kazuhiro
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: 165 Issue: 1 Pages: 337-350

    • DOI

      10.1016/j.jtcvs.2022.08.031

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transbronchial real-time lung tumor localization with folate receptor?targeted near-infrared molecular imaging: A proof of concept study in animal models2022

    • Author(s)
      Ishiwata Tsukasa、Hiraishi Yoshihisa、Bernards Nicholas、Sata Yuki、Gregor Alexander、Aragaki Masato、Yasufuku Kazuhiro
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: - Issue: 6 Pages: 01034-0

    • DOI

      10.1016/j.jtcvs.2022.09.042

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 反復光線力学的療法は、アブスコパル効果を介して胸部悪性腫瘍の遠隔転移巣を制御する-マウスモデルでの検討2023

    • Author(s)
      新垣 雅人, Lou, Jenny, Bernards Nicholas, 石綿 司, Gregor Alexander, 加藤 達哉, Zheng, Gang, 安福 和弘
    • Organizer
      第123回 日本外科学会定期学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 肺動脈血栓塞栓症に対する超音波気管支鏡下薬剤注入療法の確立を目指して―血栓溶解剤至適投与量の検討2023

    • Author(s)
      新垣雅人,稲毛輝長,石綿 司,Gregor Alexander Bernards Nicholas,加藤達哉,安福和弘
    • Organizer
      題46回 日本呼吸器内視鏡学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 免疫療法による光線力学的療法後アブスコパル効果の増強作用と免疫学的機序の解析-マウスモデルでの検討2023

    • Author(s)
      新垣 雅人, Lou Jenny, Bernards Nicholas, 石綿 司, Gregor Alexander, 加藤 達哉 Zheng Gang, 安福 和弘
    • Organizer
      第64回 日本肺癌学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Optimization of thrombolytic dose for treatment of pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection2022

    • Author(s)
      Aragaki M, Inage T, Ishiwata T, Gregor A, Bernards N, Chen Z, Yasufuku K
    • Organizer
      102nd American Association for Thoracic Surgery Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transbronchial real-time lung tumor localization with folate receptor-targeted near-infrared molecular imaging: A proof of concept study in animal models2022

    • Author(s)
      Tsukasa Ishiwata, Yoshihisa Hiraishi, Nicholas Bernards, Yuki Sata, Alexander Gregor, Masato Aragaki, Kazuhiro Yasufuku
    • Organizer
      102nd American Association for Thoracic Surgery Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping.2022

    • Author(s)
      22.Gregor A, Sata Y, Hiraishi Y, Ishiwata T, Aragaki M, Kitazawa S, Koga T, Ogawa H, Nicholas B, Yasufuku K
    • Organizer
      102nd American Association for Thoracic Surgery Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] Gang Zheng - Zheng Lab

    • URL

      http://zhenglab.utoronto.ca/publications/

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2025-01-30  

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