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Stapled peptide-based radiotheranostics for intracellular protein-protein interactions targeted cancer imaging and therapy

Research Project

Project/Area Number 21H02873
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

胡 寛  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 先進核医学基盤研究部, 研究員 (00827678)

Co-Investigator(Kenkyū-buntansha) 謝 琳  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 先進核医学基盤研究部, 主任研究員 (30623558)
破入 正行  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 先進核医学基盤研究部, 主任研究員 (80435552)
張 明栄  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 先進核医学基盤研究部, 部長 (80443076)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Declined (Fiscal Year 2022)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsstapled peptide / radiotheranostics / intracellular protein / cancer / 64Cu / radionuclide therapy / intracellular delivery / PET imaging
Outline of Research at the Start

A new kind of peptide-based radiotheranostics will be developed, denoted as stapled peptide-based radiotheranostics. They can reach the cancerous cells' plasma even the cell nucleus, and release radiation particles to destroy the DNA and RNA. Therefore, the cancerous cells can be eliminated.

Outline of Annual Research Achievements

This research project aims at the development of stapled peptide-based radiotheranostics for targeting intracellular protein protein interactions. In the past fiscal year, I developed a stapled peptide based, 64Cu labeled radiotheranostics, which can specifically bind to hDM2 in various cancer cells. The radiotheranostics, [64Cu]STP08, showed high tumor accumulation and retention in several animal models.More importantly, it significantly delayed tumor growth in mouse models and the efficacy is independent to the p53 phenotype.Biosafety study suggested that [64Cu]STP08 showed satisfactory and caused no hemotological and organ lesions in normal mice.
Moreover, we have successfully labelled STP with 225Ac, an alpha particle emitting radionuclide. The [225Ac]STP08 showed excellent treatment efficacy.

Research Progress Status

翌年度、交付申請を辞退するため、記入しない。

Strategy for Future Research Activity

翌年度、交付申請を辞退するため、記入しない。

Report

(1 results)
  • 2021 Annual Research Report
  • Research Products

    (13 results)

All 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Peking University/Nanjing Medical University/Beijing Institute of Technology(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Massachusetts General Hospital(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] A multifunctional nanotheranostic agent potentiates erlotinib to EGFR wild-type non-small cell lung cancer2022

    • Author(s)
      Wang Duo、Zhou Jun、Fang Weimin、Huang Cuiqing、Chen Zerong、Fan Meng、Zhang Ming-Rong、Xiao Zeyu、Hu Kuan、Luo Liangping
    • Journal Title

      Bioactive Materials

      Volume: 13 Pages: 312-323

    • DOI

      10.1016/j.bioactmat.2021.10.046

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptide-based nanomaterials: Self-assembly, properties and applications2022

    • Author(s)
      Li Tong、Lu Xian-Mao、Zhang Ming-Rong、Hu Kuan、Li Zhou
    • Journal Title

      Bioactive Materials

      Volume: 11 Pages: 268-282

    • DOI

      10.1016/j.bioactmat.2021.09.029

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors2022

    • Author(s)
      Hu Kuan, Wu Wenyu, Xie Lin, Geng Hao, Zhang Yiding, Hanyu Masayuki, Zhang Lulu, Liu Yinghuan, Nagatsu Kotaro, Suzuki Hisashi, Guo Jialin, Wu Yundong, Li Zigang, Wang Feng, Zhang Ming-Rong
    • Journal Title

      Acta Pharmaceutica Sinica B

      Volume: 12 Issue: 3 Pages: 1363-1376

    • DOI

      10.1016/j.apsb.2021.09.016

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a Stable Peptide-Based PET Tracer for Detecting CD133-Expressing Cancer Cells2021

    • Author(s)
      Hu Kuan、Ma Xiaohui、Xie Lin、Zhang Yiding、Hanyu Masayuki、Obata Honoka、Zhang Lulu、Nagatsu Kotaro、Suzuki Hisashi、Shi Rui、Wang Weizhi、Zhang Ming-Rong
    • Journal Title

      ACS Omega

      Volume: 7 Issue: 1 Pages: 334-341

    • DOI

      10.1021/acsomega.1c04711

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <sup>211</sup>At-Labeled Polymer Nanoparticles for Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)-Overexpressed Cancer2021

    • Author(s)
      Shi Xiumin、Li Qing、Zhang Lulu、Hanyu Masayuki、Xie Lin、Hu Kuan、Nagatsu Kotaro、Zhang Chuan、Wu Zhengcan、Wang Feng、Zhang Ming-Rong、Yang Kai、Zhu Ran
    • Journal Title

      Bioconjugate Chemistry

      Volume: 32 Issue: 8 Pages: 1763-1772

    • DOI

      10.1021/acs.bioconjchem.1c00263

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of a highly-specific 18F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping2021

    • Author(s)
      Chen Zhen、Mori Wakana、Rong Jian、Schafroth Michael A.、Shao Tuo、Van Richard S.、Ogasawara Daisuke、Yamasaki Tomoteru、Hiraishi Atsuto、Hatori Akiko、Chen Jiahui、Zhang Yiding、Hu Kuan、Fujinaga Masayuki、Sun Jiyun、Yu Qingzhen、Collier Thomas L.、et al.
    • Journal Title

      Acta Pharmaceutica Sinica B

      Volume: In press Issue: 6 Pages: 1686-1695

    • DOI

      10.1016/j.apsb.2021.01.021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In vivo PET imaging of cancer α5β1-integrin using a pegylated peptide2021

    • Author(s)
      Hu Kuan , 謝 琳 , 張 一鼎 , 破入 正行 , 張 明栄:
    • Organizer
      第61回日本核医学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Imaging urokinase plasminogen activator with a cyclic peptide-based PET tracer2021

    • Author(s)
      Hu Kuan , Xie Lin , Yiding Zhang , Hanyu Masayuki , Zhang Ming-Rong:
    • Organizer
      第61回日本核医学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of a stable peptide-based PET tracer for detecting CD133-expressing cancer stem cells2021

    • Author(s)
      Hu Kuan , Xie Lin , Yiding Zhang , Hanyu Masayuki , Obata Honoka , Nagatsu Kotaro , Suzuki Hisashi , Zhang Ming-Rong
    • Organizer
      第4回日本核医学会分科会放射線薬品科学研究会 第20回放射性医薬品・画像診断薬研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Stapled Peptide-based radiotheranostics agent targeting MDM2 suppresses p53-mutant tumor growth2021

    • Author(s)
      Hu Kuan
    • Organizer
      SNMMI2021 ANNUAL MEETING
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PEGylation modulation of peptides promotes PET detection of cancers2021

    • Author(s)
      Hu Kuan , Xie Lin , Yiding Zhang , Hanyu Masayuki , Zhang Ming-Rong
    • Organizer
      eSRS
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2022-12-28  

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