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局所療法を融合した発展型ラジオセラノスティクス用プローブ開発研究

Research Project

Project/Area Number 23K21425
Project/Area Number (Other) 21H02867 (2021-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2021-2023)
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKanazawa University

Principal Investigator

小川 数馬  金沢大学, 新学術創成研究機構, 教授 (30347471)

Co-Investigator(Kenkyū-buntansha) 瀧 淳一  金沢大学, 医学系, 協力研究員 (10251927)
仁宮 一章  金沢大学, 新学術創成研究機構, 教授 (10379125)
三代 憲司  金沢大学, 新学術創成研究機構, 准教授 (60776079)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Declined (Fiscal Year 2024)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2024: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsセラノスティクス / イメージング / がん / 内用療法 / モダリティ / ラジオセラノスティクス / 核医学治療
Outline of Research at the Start

放射性同位元素(RI)を用いて診断治療を一体化して展開するラジオセラノスティクスは、個別化医療を実現している治療法であるが、診断・治療用RIの組み合わせは限定される。一方、核医学治療と他の局所治療法との併用はほとんど報告がないが、局所療法は相補的に機能すると考えた。そこで、本研究では、ラジオセラノスティクスを発展させるべく、通常の手法では組み合わせ不可能な核種を組み合わせたラジオセラノスティクス用プローブ開発を行い、次いで、局所療法とを組み合わせた新規プローブ開発を行い、有用性を評価する。

Outline of Annual Research Achievements

本年度は、標的アルファ線治療用化合物として、At-211標識シグマ受容体標的プローブ[211At]mAtC2N5Vと[211At]mAtC3N5Vの開発に成功し、評価を行った。[211At]mAtC2N5Vと[211At]mAtC3N5Vは、それぞれDU-145担がんマウスの腫瘍に高く集積し(6.9 ± 1.4%injected dose/g and 5.1 ± 1.4%injected dose/g at 1 h, respectively)、対応するヨウ素標識プローブと類似の体内動態を示した。一方、0.48 MBqの単回投与で腫瘍増殖を有意に抑制し、ラジオセラノスティクス用プローブとしての可能性を示した。
また、他の治療モダリティに関しては、porphyrin結合ナノ液滴の合成、評価を行った。その結果、プローブ投与後の超音波照射により、担がんマウスの腫瘍増殖を有意に抑制した。この結果は、本プローブの超音波力学療法用プローブとしての有用性を示すものである(論文投稿中)。
また、Glaペプチドの新しい骨輸送担体としての有用性を評価した。研究代表者は、これまでにAspペプチドやGluペプチドの骨輸送担体として有用性を示してきたが、GlaペプチドはAspペプチドやGluペプチドよりも骨指向性が高く、骨輸送担体として優れていることが示された。今後、この輸送担体を利用したマルチモダリティのラジオセラノスティクス用プローブを開発していく。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (24 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Adam Mickiewicz University(ポーランド)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Shanghai University(中国)

    • Related Report
      2023 Annual Research Report
  • [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] Development of Radiohalogenated Osimertinib Derivatives as Imaging Probes for Companion Diagnostics of Osimertinib2022

    • Author(s)
      Mishiro K, Nishii R, Sawazaki I, Sofuku T, Fuchigami T, Sudo H, Effendi N, Makino A, Kiyono Y, Shiba K, Taki J, Kinuya S, Ogawa K.
    • Journal Title

      J Med Chem

      Volume: 65 Issue: 3 Pages: 1835-1847

    • DOI

      10.1021/acs.jmedchem.1c01211

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides2021

    • Author(s)
      Ogawa K, Echigo H, Mishiro K, Hirata S, Washiyama K, Kitamura Y, Takahashi K, Shiba K, Kinuya S.
    • Journal Title

      Molecular Pharmaceutics

      Volume: 18(9) Issue: 9 Pages: 3553-3562

    • DOI

      10.1021/acs.molpharmaceut.1c00460

    • Related Report
      2021 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [Presentation] がんセラノスティクスを目的としたプローブ開発2023

    • Author(s)
      小川数馬
    • Organizer
      第32回ソノケミストリー討論会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Development of Probes for Cancer Radiotheranostic2023

    • Author(s)
      Kazuma Ogawa
    • Organizer
      The 2nd Makassar International Conference on Pharmaceutical Sciences (MICPS) 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of new bone-seeking radiolabeled compounds.2023

    • Author(s)
      K. Ogawa, K. Nishizawa, K. Mishiro, N. Effendi, T. Fuchigami, M. Munekane, K. Washiyama, S. Kinuya.
    • Organizer
      36th Annual Congress of European Association of Nuclear Medicine
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a radiotheranostics agent with albumin binder aiming to increase the therapeutic effects for At-211 labeled RGD peptide2023

    • Author(s)
      H. Echigo, K. Mishiro, K. Washiyama, T. Fuchigami, M. Munekane, K. Takahashi, M. Kunishima, S. Kinuya., K. Ogawa
    • Organizer
      The 25th International Symposium of Radiopharmaceutical Sciences
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Targeted Alpha Therapy (TAT) の現状と未来2023

    • Author(s)
      小川数馬
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Targeted alpha therapy using At-211-labeled Sigma receptor ligands2023

    • Author(s)
      K. Ogawa, K. Nishizawa, K. Washiyama, K. Mishiro, M. Munekane, T. Fuchigami, K. Takahashi, S. Kinuya
    • Organizer
      12th International Symposium on Targeted Alpha Therapy (TAT12)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 短寿命アルファ核種の利用研究の現状と可能性2021

    • Author(s)
      小川 数馬
    • Organizer
      第3回日本放射線安全管理学会・日本保健物理学会合同大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      https://www.p.kanazawa-u.ac.jp/research/lab/12.html#gsc.tab=0

    • Related Report
      2022 Annual Research Report
  • [Remarks]

    • URL

      https://infiniti.adm.kanazawa-u.ac.jp/core/kakusin04.php

    • Related Report
      2022 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2022 Annual Research 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
      2023 Annual Research Report 2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 放射性同位元素含有化合物、及びそれを含む骨用医薬2023

    • Inventor(s)
      小川数馬、三代憲司、淵上剛志、宗兼将之
    • Industrial Property Rights Holder
      小川数馬、三代憲司、淵上剛志、宗兼将之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-026987
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report

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Published: 2021-04-28   Modified: 2024-12-25  

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