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Development of molecular imaging tools to specifically capture the pathological dynamics of viral infections

Research Project

Project/Area Number 21K19452
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKanazawa University

Principal Investigator

Fuchigami Takeshi  金沢大学, 薬学系, 准教授 (30432206)

Co-Investigator(Kenkyū-buntansha) ヌグエ・トン ミャ・ミャッ  長崎大学, 熱帯医学研究所, 客員研究員 (90772583)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords分子イメージング / ウイルス / SPECT / 抗体 / N-タンパク質 / Nタンパク質 / 感染症
Outline of Research at the Start

本研究では、未だ病態発現機構が明らかでない新興再興感染症を引き起こすウイルスによる感染症の経時的な病態の進行過程をライブイメージングできる新規技術の開発を目的とした。そこで、(1) ウイルス由来タンパク質に極めて特異的な抗体型分子プローブを用いたin vivoイメージング、(2) ウイルス発現に応じて酵素やトランスポーターを発現するレポーター遺伝子を利用したin vivoイメージングの2つの手法を開発し、ウイルス感染症選択的な病態解析法として資するか検討する。

Outline of Final Research Achievements

The real-time analysis of disease progression through infection-specific molecular imaging is highly anticipated in the context of viral infections. In this study, we developed and evaluated imaging probes targeting the virus (SFTSV) responsible for SFTS, which has a mortality rate exceeding 10%. Among various antibodies tested against SFTSV-infected cells, the N protein-targeting IgG (N-mAb) demonstrated the most promising binding properties. In vivo evaluations, including SPECT/CT, confirmed high accumulation of 111In-N-mAb at virus-infected sites in infected mice, indicating that 111In-N-mAb functions as an SFTSV-selective imaging probe. Future work will focus on analyzing the correlation between disease severity and the behavior of infection molecules, as well as developing therapeutic strategies.

Academic Significance and Societal Importance of the Research Achievements

未解明なウイルス感染症の分子イメージングにより、詳細な病態進行のメカニズム解析が可能となり、早期診断や治療法の確立に繋がることが期待される。
本研究では、罹患すれば致死率が10%を超え、日本でも大きな問題となっている新興感染症のSFTSを研究対象として、感染分子特異的な分子プローブの開発を試みた。その結果、Nタンパク質というSFTSウイルスの内部および表面に発現している特異的な抗原を認識する抗体を用いることで、生体内におけるSFTSV挙動の特異的な分子イメージングが可能であることを発見した。本研究成果は、様々な新興・再興感染症の病態解明や治療法開発への応用が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (26 results)

All 2024 2023 2022 2021 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 12 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Development of the Precision-designed Radiopharmaceuticals Depending on the Targeting Molecules2024

    • Author(s)
      淵上 剛志
    • Journal Title

      RADIOISOTOPES

      Volume: 73 Issue: 2 Pages: 139-145

    • DOI

      10.3769/radioisotopes.73.139

    • ISSN
      0033-8303, 1884-4111
    • Year and Date
      2024-07-15
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone2024

    • Author(s)
      Ogawa K, Nishizawa K, Mishiro K, Effendi N, Fuchigami T, Munekane M, Wakabayashi H, Kinuya S.
    • Journal Title

      Mol Pharm

      Volume: 21 Issue: 5 Pages: 2375-2382

    • DOI

      10.1021/acs.molpharmaceut.3c01156

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimizing the pharmacokinetics of an 211At-labeled RGD peptide with an albumin-binding moiety via the administration of an albumin-binding inhibitor2024

    • Author(s)
      Echigo H, Munekane M, Fuchigami T, Washiyama K, Mishiro K, Wakabayashi H, Takahashi K, Kinuya S, Ogawa K.
    • Journal Title

      Eur J Nucl Med Mol Imaging

      Volume: - Issue: 9 Pages: 2663-2671

    • DOI

      10.1007/s00259-024-06695-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent advances in the development of 225Ac- and 211At-labeled radioligands for radiotheranostics2024

    • Author(s)
      Munekane M, Fuchigami T, Ogawa K.
    • Journal Title

      Anal Sci

      Volume: 40 Issue: 5 Pages: 803-826

    • DOI

      10.1007/s44211-024-00514-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At)2024

    • Author(s)
      Echigo H, Mishiro K, Munekane M, Fuchigami T, Washiyama K, Takahashi K, Kitamura Y, Wakabayashi H, Kinuya S, Ogawa K.
    • Journal Title

      Eur J Nucl Med Mol Imaging

      Volume: 51 Issue: 2 Pages: 412-421

    • DOI

      10.1007/s00259-023-06457-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astatine-211-labeled aza-vesamicol derivatives as sigma receptor ligands for targeted alpha therapy2023

    • Author(s)
      Ogawa K, Nishizawa K, Washiyama K, Munekane M, Fuchigami T, Echigo H, Mishiro K, Hirata S, Wakabayashi H, Takahashi K, Kinuya S.
    • Journal Title

      Nucl Med Biol

      Volume: 122-123 Pages: 108369-108369

    • DOI

      10.1016/j.nucmedbio.2023.108369

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation and Evaluation of Thermosensitive Liposomes Encapsulating I-125-Labeled Doxorubicin Derivatives for Auger Electron Therapy2023

    • Author(s)
      Elghobary Mohamed Elsaid Nasr、Munekane Masayuki、Mishiro Kenji、Fuchigami Takeshi、Ogawa Kazuma
    • Journal Title

      Molecules

      Volume: 28 Issue: 4 Pages: 1864-1864

    • DOI

      10.3390/molecules28041864

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits2022

    • Author(s)
      Nakaie Mari、Katayama Fumihiro、Nakagaki Takehiro、Kawasaki Masao、Yoshida Sakura、Toriba Akira、Ogawa Kazuma、Nishida Noriyuki、Nakayama Morio、Fuchigami Takeshi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 3 Pages: 211-219

    • DOI

      10.1248/cpb.c21-00902

    • NAID

      130008165517

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-03-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and Biological Evaluation of Novel 2-(Benzofuran-2-yl)-chromone Derivatives for In Vivo Imaging of Prion Deposits in the Brain2022

    • Author(s)
      Nakaie Mari、Katayama Fumihiro、Nakagaki Takehiro、Yoshida Sakura、Kawasaki Masao、Nishi Kodai、Ogawa Kazuma、Toriba Akira、Nishida Noriyuki、Nakayama Morio、Fuchigami Takeshi
    • Journal Title

      ACS Infectious Diseases

      Volume: 8 Issue: 9 Pages: 1869-1882

    • DOI

      10.1021/acsinfecdis.2c00142

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development and evaluation of a theranostic probe with RGD peptide introduced platinum complex to enable tumor-specific accumulation2022

    • Author(s)
      Echigo Hiroaki、Mishiro Kenji、Munekane Masayuki、Fuchigami Takeshi、Kitamura Yoji、Kinuya Seigo、Ogawa Kazuma
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 70 Pages: 116919-116919

    • DOI

      10.1016/j.bmc.2022.116919

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and evaluation of a multifunctional probe with a high affinity for prostate-specific membrane antigen (PSMA) and bone2022

    • Author(s)
      Hirata Saki、Mishiro Kenji、Higashi Takuma、Fuchigami Takeshi、Munekane Masayuki、Arano Yasushi、Kinuya Seigo、Ogawa Kazuma
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 114-115 Pages: 34-41

    • DOI

      10.1016/j.nucmedbio.2022.08.004

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Borealin-Derived Peptides as Survivin-Targeting Cancer Imaging and Therapeutic Agents2022

    • Author(s)
      Nozaki Iori、Ishikawa Natsumi、Miyanari Yusuke、Ogawa Kazuma、Tagawa Ayako、Yoshida Sakura、Munekane Masayuki、Mishiro Kenji、Toriba Akira、Nakayama Morio、Fuchigami Takeshi
    • Journal Title

      Bioconjugate Chemistry

      Volume: 33 Issue: 11 Pages: 2149-2160

    • DOI

      10.1021/acs.bioconjchem.2c00398

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] RGD Peptide-Conjugated Dodecaborate with the Ga-DOTA Complex: A Preliminary Study for the Development of Theranostic Agents for Boron Neutron Capture Therapy and Its Companion Diagnostics2022

    • Author(s)
      Mishiro Kenji、Imai Sayaka、Ematsu Yuki、Hirose Katsumi、Fuchigami Takeshi、Munekane Masayuki、Kinuya Seigo、Ogawa Kazuma
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 65 Issue: 24 Pages: 16741-16753

    • DOI

      10.1021/acs.jmedchem.2c01586

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and evaluation of radiolabeled porphyrin derivatives for cancer diagnoses and their nonradioactive counterparts for photodynamic therapy2022

    • Author(s)
      Ramzi Nur Izni、Mishiro Kenji、Munekane Masayuki、Fuchigami Takeshi、Hu Xiaojun、Jastrz?b Renata、Kitamura Yoji、Kinuya Seigo、Ogawa Kazuma
    • Journal Title

      RSC Medicinal Chemistry

      Volume: 13 Issue: 12 Pages: 1565-1574

    • DOI

      10.1039/d2md00234e

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of tumor-targeting aza-vesamicol derivatives with high affinity for sigma receptors for cancer theranostics2022

    • Author(s)
      Mishiro Kenji、Wang Mengfei、Hirata Saki、Fuchigami Takeshi、Shiba Kazuhiro、Kinuya Seigo、Ogawa Kazuma
    • Journal Title

      RSC Medicinal Chemistry

      Volume: 13 Issue: 8 Pages: 986-997

    • DOI

      10.1039/d2md00099g

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2021年度日本アイソトープ協会シンポジウム 印象記2022

    • Author(s)
      淵上 剛志
    • Journal Title

      Isotope News

      Volume: 780 Pages: 42-43

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens.2021

    • Author(s)
      Hiroaki Echigo, Kenji Mishiro, Takeshi Fuchigami, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa
    • Journal Title

      Molecules (Basel, Switzerland)

      Volume: 26 Issue: 20 Pages: 6107-6107

    • DOI

      10.3390/molecules26206107

    • NAID

      120007185672

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] がんおよび感染症の特異的診断を目指した分 子プローブの開発と核医学治療への展開2023

    • Author(s)
      淵上 剛志
    • Organizer
      第60回 アイソトープ・放射線研究発表会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 疾患や標的分子の特性に応じて精密設計した RIプローブの開発2023

    • Author(s)
      淵上 剛志
    • Organizer
      第60回 アイソトープ・放射線研究発表会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Preparation and evaluation of an ADAM8-targeted 111In-labeled antibody for the detection of early pancreatic cancer2023

    • Author(s)
      T. Fuchigami, T. Kosugi, Y. Miyanari, A. Tagawa, T. Adachi, K. Nishi, S. Yoshida, K. Mishiro, M. Munekane, A. Toriba, K. Ogawa
    • Organizer
      The 25th International Symposium of Radiopharmaceutical Sciences
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of imaging probes for cancers and infectious diseases and their prospective in theranostics agents2023

    • Author(s)
      Takeshi Fuchigami, Kazuma Ogawa
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of heterodivalent molecular probes targeting negative charge and integrin on the surface of cancer cell membrane.2022

    • Author(s)
      T. Fuchigami, K. Shimo, K. Mishiro, M. Munekane, Y. Kitamura, S. Kinuya, K. Ogawa
    • Organizer
      13th Congress of the World Federation of Nuclear Medicine and Biology (WFNMB 2022)
    • Related Report
      2022 Research-status Report
  • [Book] Cell-Penetrating Peptides: Design, Development and Applications2022

    • Author(s)
      Takeshi Fuchigami, Masayuki Munekane, Kazuma Ogawa (Editor , Makoto Oba, Yosuke Demizu)
    • Total Pages
      416
    • Publisher
      Wiley
    • ISBN
      9783527350117
    • Related Report
      2022 Research-status Report
  • [Remarks] 金沢大学薬学 臨床分析科学 研究室

    • URL

      https://www.p.kanazawa-u.ac.jp/~bunseki/

    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 膵臓がん抗原に対するVHH抗体及び膵臓がん細胞検出方法2023

    • Inventor(s)
      淵上剛志, 宮成悠介, 田川綾子, 小川数馬,他
    • Industrial Property Rights Holder
      淵上剛志, 宮成悠介, 田川綾子, 小川数馬,他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-032216
    • Filing Date
      2023
    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] 放射性同位体標識診療薬剤2023

    • Inventor(s)
      小川数馬、三代憲司、越後拓亮、淵上剛志、宗兼将之
    • Industrial Property Rights Holder
      小川数馬、三代憲司、越後拓亮、淵上剛志、宗兼将之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-032034
    • Filing Date
      2023
    • Related Report
      2022 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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