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In vivo oxygen mapping based on lifetime imaging microscopy using phosphorescent molecule

Research Project

Project/Area Number 19K22947
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionGunma University

Principal Investigator

Yoshihara Toshitada  群馬大学, 大学院理工学府, 准教授 (10375561)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsりん光 / りん光寿命 / 酸素 / イリジウム錯体 / 細胞 / 組織 / 寿命イメージング
Outline of Research at the Start

本研究では,血中から組織細胞内に移行するカチオン性Ir錯体を開発し,共焦点りん光寿命イメージング顕微鏡を用いて,組織内(肝臓,腎臓,腫瘍など)の酸素濃度(分圧)を単一細胞レベルの分解能でリアルタイムイメージングする方法論を確立する。これにより,医学分野において指摘されてきた生きた組織内の酸素濃度勾配を細胞レベルの分解能で定量することに挑戦する。

Outline of Final Research Achievements

In this study, we designed and synthesized intracellular oxygen probes based on red phosphorescent iridium complexes for sensing of oxygen levels in living cells and tissues, and a confocal phosphorescence lifetime imaging microscope (PLIM) for the measurements of oxygen partial pressure of mice was developed. Using these oxygen probes and PLIM, the detection and visualization of oxygen levels of hepatic lobules were succeeded. The PLIM images clearly visualized the oxygen gradient in hepatic lobules with cellular level resolution. Furthermore, we succeeded in real-time tracking of oxygen-dependent metabolic processes based on phosphorescence lifetime imaging of the liver in the same field of view.

Academic Significance and Societal Importance of the Research Achievements

酸素は、我々が生命活動を維持するために必要不可欠な分子です。本研究では、麻酔下にあるマウスの臓器内の酸素分圧を計測・イメージングする方法論の開発に取り組みました。得られた研究成果から、世界で初めて、光学的方法を用いて肝臓内の酸素分圧分布をイメージングすることに成功しました。この知見は,がん腫瘍など,細胞が異常増殖し血流が不十分な組織内の酸素分圧を明らかにすることに繋がり,がんの発見,診断,治療法の開発に貢献することができます。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (5 results) Book (3 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Phosphorescent Ir(III) complexes conjugated with oligoarginine peptides serve as optical probes for in vivo microvascular imaging2021

    • Author(s)
      Yasukagawa Mami、Shimada Aya、Shiozaki Shuichi、Tobita Seiji、Yoshihara Toshitada
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4733-4733

    • DOI

      10.1038/s41598-021-84115-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane properties of amacrocyclic tetraether bisphosphatidylcholine lipid: Effect of a single membrane-spanning polymethylene cross-linkage between two head groups of ditetradecylphosphatidylcholine membrane2021

    • Author(s)
      Tsuchida Naoyuki、Takagi Toshiyuki、Takahashi Hiroshi、Yoshihara Toshitada、Tobita Seiji、Sonoyama Masashi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1863 Issue: 5 Pages: 183569-183569

    • DOI

      10.1016/j.bbamem.2021.183569

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the triplet-state kinetics of a photosensitizer for photoimmunotherapy by fluorescence correlation spectroscopy2021

    • Author(s)
      Takakura Hideo、Goto Yuto、Kitamura Akira、Yoshihara Toshitada、Tobita Seiji、Kinjo Masataka、Ogawa Mikako
    • Journal Title

      Journal of Photochemistry and Photobiology A: Chemistry

      Volume: 408 Pages: 113094-113094

    • DOI

      10.1016/j.jphotochem.2020.113094

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A distinctive distribution of hypoxia-inducible factor-1α in cultured renal tubular cells with hypoperfusion simulated by coverslip placement2021

    • Author(s)
      Honda T, Hirakawa Y, Mizukami K, Yoshihara T, Tanaka T, Tobita S, Nangaku M
    • Journal Title

      Physiol Rep

      Volume: 9 Issue: 1

    • DOI

      10.14814/phy2.14689

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo O2 imaging in hepatic tissues by phosphorescence lifetime imaging microscopy using Ir(III) complexes as intracellular probes2020

    • Author(s)
      Mizukami Kiichi、Katano Ayaka、Shiozaki Shuichi、Yoshihara Toshitada、Goda Nobuhito、Tobita Seiji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21053-21053

    • DOI

      10.1038/s41598-020-76878-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design of spontaneously blinking fluorophores for live-cell super-resolution imaging based on quantum-chemical calculations2020

    • Author(s)
      Tachibana Ryo、Kamiya Mako、Morozumi Akihiko、Miyazaki Yoshiyuki、Fujioka Hiroyoshi、Nanjo Aika、Kojima Ryosuke、Komatsu Toru、Ueno Tasuku、Hanaoka Kenjiro、Yoshihara Toshitada、Tobita Seiji、Urano Yasuteru
    • Journal Title

      Chemical Communications

      Volume: 56 Issue: 86 Pages: 13173-13176

    • DOI

      10.1039/d0cc05126h

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneously Blinking Fluorophores Based on Nucleophilic Addition/Dissociation of Intracellular Glutathione for Live-Cell Super-resolution Imaging2020

    • Author(s)
      Morozumi Akihiko、Kamiya Mako、Uno Shin-nosuke、Umezawa Keitaro、Kojima Ryosuke、Yoshihara Toshitada、Tobita Seiji、Urano Yasuteru
    • Journal Title

      Journal of the American Chemical Society

      Volume: - Pages: 9625-9633

    • DOI

      10.1021/jacs.0c00451

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of Lipid Droplets in Living Cells and Fatty Livers of Mice Based on the Fluorescence of π-Extended Coumarin Using Fluorescence Lifetime Imaging Microscopy2020

    • Author(s)
      Yoshihara Toshitada、Maruyama Ryo、Shiozaki Shuichi、Yamamoto Koji、Kato Shin-ichiro、Nakamura Yosuke、Tobita Seiji
    • Journal Title

      Analytical Chemistry

      Volume: 92 Issue: 7 Pages: 4996-5003

    • DOI

      10.1021/acs.analchem.9b05184

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] クマリン類を配位子に有するイリジウム錯体を用いた生体内酸素レベル計測2021

    • Author(s)
      吉原 利忠・広瀬 達也・塩崎 秀一・飛田 成史
    • Organizer
      第42回日本光医学・光生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Visualization of hypoxia cells in tissues by using phosphorescence lifetime imaging microscopy2020

    • Author(s)
      Toshitada YOSHIHARA
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 蛍光寿命イメージング顕微分光法を用いた細胞および組織内脂質滴のライブイメージング2020

    • Author(s)
      吉原 利忠 ・ 丸山 凌 ・ 塩崎 秀一 ・ 飛田 成史
    • Organizer
      2020年web光化学討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] イリジウム錯体を用いた生体組織 内微小環境の酸素イメージング2019

    • Author(s)
      水上輝市,片野彩花,塩崎秀一,吉原利忠,飛田成史
    • Organizer
      第17回がんとハイポキシア研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Ir(III)錯体および共焦点りん光寿命イメージング法を用いた脂肪肝の酸素イメージング2019

    • Author(s)
      Purevsuren Khulan,塩崎秀一,吉原利忠,飛田成史
    • Organizer
      第17回がんとハイポキシア研究会
    • Related Report
      2019 Research-status Report
  • [Book] BIO INDUSTRY2021年3月号2021

    • Author(s)
      吉原利忠(分担執筆)
    • Total Pages
      86
    • Publisher
      シーエムシー出版
    • Related Report
      2020 Annual Research Report
  • [Book] 化学便覧 基礎編 改訂6版2021

    • Author(s)
      吉原利忠、飛田成史(分担執筆)
    • Total Pages
      1534
    • Publisher
      丸善出版
    • ISBN
      9784621305218
    • Related Report
      2020 Annual Research Report
  • [Book] 実験医学2020年6月号2020

    • Author(s)
      吉原利忠、飛田成史(分担執筆)
    • Total Pages
      147
    • Publisher
      羊土社
    • ISBN
      9784758125321
    • Related Report
      2020 Annual Research Report
  • [Remarks] 群馬大学理工学府分子科学部門 吉原研究室

    • URL

      https://tobita-lab.chem-bio.st.gunma-u.ac.jp/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 群馬大学理工学府分子科学部門 飛田研究室

    • URL

      https://tobita-lab.chem-bio.st.gunma-u.ac.jp/

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 血管内皮イメージング試薬2020

    • Inventor(s)
      吉原利忠、安カ川真美、鷲見さくら、飛田成史
    • Industrial Property Rights Holder
      吉原利忠、安カ川真美、鷲見さくら、飛田成史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-211560
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] REAGENT FOR MEASURING OXYGEN CONCENTRATION IN CELL AND TISSUE2020

    • Inventor(s)
      吉原利忠、広瀬達也、飛田成史
    • Industrial Property Rights Holder
      吉原利忠、広瀬達也、飛田成史
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas

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Published: 2019-07-04   Modified: 2022-01-27  

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