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Synthesis and evaluation of radioactive nanometallic agents that specifically recognize pancreatic cancer cells

Research Project

Project/Area Number 18K07281
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

HANYU Masayuki  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)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsCu-64 / At-211 / 標識方法 / ナノ粒子 / 銅-64 / 環状ペプチド / 放射性金属核種 / PET / PET核種 / 標識反応
Outline of Final Research Achievements

The aim of this study is to find a method to efficiently label nanoparticle systems with radionuclides and then introduce biological small molecules or biological macromolecules, which will be useful for the molecular design of future radiopharmaceuticals. The nanoparticulation was confirmed to be in progress with a yield of about 10%. PEG chains could be introduced into the nanoparticles by dispersing them with ultrasound. When isoDGR was labeled with Cu-64, it was found to accumulate in cancer cells but was quickly excreted into the kidney.

Academic Significance and Societal Importance of the Research Achievements

ナノ粒子化を利用した治療薬剤の開発は2000年代から研究報告が増大しており、その製剤は約30品目以上が市場にでている。すなわち今後さらに発展する可能性を秘めている。一般的に、ナノ粒子は大きな分子構造の変更なく複数の機能を組み込むことが可能であり治療と診断を融合させるには良好な素材である。そこでナノ粒子系中に効率よく放射性核種で位置特異的な標識を行い、放射性ナノ薬剤の分子設計の指標に大いに役立つことができると考えた。本研究ではCu-64とAt-211の放射性核種のナノ粒子が調製可能であることを見出したが、さらなる検討が必要であることも明らかとなった。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 7 results)

  • [Journal Article] Automated radiosynthesis of [11C]MTP38-a phosphodiesterase 7 imaging tracer using [11C]hydrogen cyanide for clinical applications2022

    • Author(s)
      Kawamura Kazunori、Hashimoto Hiroki、Ohkubo Takayuki、Hanyu Masayuki、Ogawa Masanao、Nengaki Nobuki、Arashi Daisuke、Kurihara Yusuke、Fujishiro Tomoya、Togashi Takahiro、Sakai Toshiyuki、Muto Masatoshi、Takei Makoto、Ishii Hideki、Saijo Takeaki、Matsumura Takehiko、Obokata Naoyuki、Zhang Ming‐Rong
    • Journal Title

      Journal of Labelled Compounds and Radiopharmaceuticals

      Volume: 65 Issue: 5 Pages: 140-146

    • DOI

      10.1002/jlcr.3965

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin2021

    • Author(s)
      Ohkubo Takayuki、Kurihara Yusuke、Ogawa Masanao、Nengaki Nobuki、Fujinaga Masayuki、Mori Wakana、Kumata Katsushi、Hanyu Masayuki、Furutsuka Kenji、Hashimoto Hiroki、Kawamura Kazunori、Zhang Ming-Rong
    • Journal Title

      EJNMMI Radiopharmacy and Chemistry

      Volume: 6 Issue: 1 Pages: 23-23

    • DOI

      10.1186/s41181-021-00138-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint2020

    • Author(s)
      Hu Kuan、Xie Lin、Hanyu Masayuki、Zhang Yiding、Li Lingyun、Ma Xiaohui、Nagatsu Kotaro、Suzuki Hisashi、Wang Weizhi、Zhang Ming-Rong
    • Journal Title

      RSC Chemical Biology

      Volume: 1 Issue: 4 Pages: 214-224

    • DOI

      10.1039/d0cb00070a

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy2020

    • Author(s)
      Hu Kuan、Xie Lin、Zhang Yiding、Hanyu Masayuki、Yang Zhimin、Nagatsu Kotaro、Suzuki Hisashi、Ouyang Jiang、Ji Xiaoyuan、Wei Junjie、Xu Hao、Farokhzad Omid C.、Liang Steven H.、Wang Lu、Tao Wei、Zhang Ming-Rong
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 2778-2778

    • DOI

      10.1038/s41467-020-16513-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PET Imaging of VEGFR with a Novel 64Cu-Labeled Peptide2020

    • Author(s)
      Hu Kuan、Shang Jingjie、Xie Lin、Hanyu Masayuki、Zhang Yiding、Yang Zhimin、Xu Hao、Wang Lu、Zhang Ming-Rong
    • Journal Title

      ACS Omega

      Volume: 5 Issue: 15 Pages: 8508-8514

    • DOI

      10.1021/acsomega.9b03953

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiosynthesis and evaluation of 4-(6-[18F]Fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine as a novel radiotracer candidate targeting leucine-rich repeat kinase 22020

    • Author(s)
      Mori Wakana、Yamasaki Tomoteru、Hattori Yasushi、Zhang Yiding、Kumata Katsushi、Fujinaga Masayuki、Hanyu Masayuki、Nengaki Nobuki、Zhang Hong、Zhang Ming-Rong
    • Journal Title

      RSC Medicinal Chemistry

      Volume: 11 Issue: 6 Pages: 676-684

    • DOI

      10.1039/c9md00590k

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Radiosynthesis of [thiocarbonyl-11C]disulfiram and its first PET study in mice2020

    • Author(s)
      Ishii Hideki、Yamasaki Tomoteru、Yui Joji、Zhang Yiding、Hanyu Masayuki、Ogawa Masanao、Nengaki Nobuki、Tsuji Atsushi B.、Terashima Yuya、Matsushima Kouji、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: - Issue: 6 Pages: 126998-126998

    • DOI

      10.1016/j.bmcl.2020.126998

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simple separation of 67Cu from bulk zinc by coprecipitation using hydrogen sulfide gas and silver nitrate2020

    • Author(s)
      Tomoyuki Ohya, Kotaro Nagatsu, Masayuki Hanyu, Katsuyuki Minegishi, Ming-Rong Zhang
    • Journal Title

      Radiochimica Acta

      Volume: - Issue: 6 Pages: 469-476

    • DOI

      10.1515/ract-2019-3168

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 131I-IITM and 211At-AITM: Two Novel Small-Molecule Radiopharmaceuticals Targeting Oncoprotein Metabotropic Glutamate Receptor 12019

    • Author(s)
      Xie Lin、Hanyu Masayuki、Fujinaga Masayuki、Zhang Yiding、Hu Kuan、Minegishi Katsuyuki、Jiang Cuiping、Kurosawa Fuki、Morokoshi Yukie、Li Huizi Keiko、Hasegawa Sumitaka、Nagatsu Kotaro、Zhang Ming-Rong
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 61 Issue: 2 Pages: 242-248

    • DOI

      10.2967/jnumed.119.230946

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of a remote purification apparatus with disposable evaporator for the routine production of high-quality 64Cu for clinical use2019

    • Author(s)
      Ohya Tomoyuki、Minegishi Katsuyuki、Suzuki Hisashi、Nagatsu Kotaro、Fukada Masami、Hanyu Masayuki、Zhang Ming-Rong
    • Journal Title

      Applied Radiation and Isotopes

      Volume: 146 Pages: 127-132

    • DOI

      10.1016/j.apradiso.2019.01.024

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Developing native peptide-based radiotracers for PD-L1 PET imaging and improving imaging contrast by pegylation2019

    • Author(s)
      Kuan Hu、Masayuki Hanyu、Xie Lin、Zhang Yiding、Kotaro Nagatsu、Hisashi Suzuki、Zhang Ming-Rong
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 29 Pages: 4162-4165

    • DOI

      10.1039/c9cc00445a

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] TRT薬剤「211At-AITM」合成法の改良2021

    • Author(s)
      破入 正行, 峯岸 克行, 門間 あゆみ, 謝 琳, Hu Kuan, 張 一鼎, 藤永 雅之, 永津 弘太郎, 張 明栄
    • Organizer
      第61回日本核医学会学術総会, 日本核医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] RADIOLABELLING AND PET IMAGING OF COPPER-64 LABELED ISODGR DERIVATIVE2020

    • Author(s)
      Masayuki Hanyu, Lin Xie, Hu Kuan, Yiding Zhang, Ming-Rong Zhang
    • Organizer
      第57回ペプチド討論会, 日本ペプチド学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 癌蛋白質mGluR1に基づくがん種横断的な211At-AITM標的アイソトープ治療法の開発2020

    • Author(s)
      謝 琳, 張 露露, 破入 正行, 藤永 雅之, 張 一鼎, 峯岸 克行, Hu Kuan, 李 惠子, 長谷川 純崇, 永津 弘太郎, 張 明栄
    • Organizer
      第60回日本核医学会学術総会, 日本核医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Harnessing PD-L1 interface peptide for PET imaging of PD-1 immune checkpoint2020

    • Author(s)
      Hu Kuan, Lin Xie, Yiding Zhang, Masayuki Hanyu, Ming-Rong Zhang
    • Organizer
      第60回日本核医学会学術総会, 日本核医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ET Imaging of VEGFR with a Novel 64Cu Labeled Peptide2020

    • Author(s)
      Hu Kuan, Lin Xie, Yiding Zhang, Masayuki Hanyu, Ming-Rong Zhang
    • Organizer
      第60回日本核医学会学術総会, 日本核医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Positron Emission Tomography Imaging of Vascular Endothelial Growth Factor Receptor Expression with a new 64Cu labeled peptide2020

    • Author(s)
      Hu Kuan, Jingjie Shang, Lin Xie, Masayuki Hanyu, Yiding Zhang, Zhimin Yang, Hao Xu, Wang Lu, Ming-Rong Zhang
    • Organizer
      SNMMI 2020 Annual Meeting, Society of Nuclear Medicine and Molecular Imaging
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] HPLCポストカラム法を用いたPET薬剤中の金属不純物の定量2019

    • Author(s)
      破入正行, 石井英樹, 念垣信樹, 小川政直, 嵐大輔, 古塚賢士, 橋本裕輝, 河村和紀, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 転移性メラノーマに対する211At-AITMによる標的アイソトープ治療薬としての実証2019

    • Author(s)
      謝琳, 破入正行, 藤永雅之, 張一鼎, 峯岸克行, 李惠子, 諸越幸恵, 長谷川純崇, 永津弘太郎, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 承認申請を見据えた[64Cu]Cu-ATSM注射液の品質検査法の設定2019

    • Author(s)
      橋本裕輝, 破入正行, 大久保崇之, 河村和紀, 吉井幸恵, 脇厚生, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 共沈を用いたバルクZnターゲットからの67Cu分離精製法2019

    • Author(s)
      大矢智幸, 永津弘太郎, 破入正行, 峯岸克行, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effective therapy against melanoma using 211At labeled small-molecule radiopharmaceutical 211At-AITM by targeting oncoprotein metabotropic glutamate receptor 12019

    • Author(s)
      Lin Xie, Masayuki Hanyu, Masayuki Fujinaga, Yiding Zhang, Hu Kuan, Katsuyuki Minegishi, Cuiping Jiang, Fuki Kurosawa, Yukie Morokoshi, Huizi Li, Sumitaka Hasegawa, Kotaro Nagatsu, Ming-Rong Zhang
    • Organizer
      World Molecular Imaging Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Radiolabeling and evaluation of isoDGR derivative using radioactive cooper2019

    • Author(s)
      Masayuki Hanyu, Lin Xie, Hu Kuan, Zhimin Yang, Yiding Zhang, Hisashi Suzuki, Ming-Rong Zhang
    • Organizer
      14th International Conference on Radiopharmaceutical Therapy
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Measurement of the metal impurity in PET probe using the HPLC post-column method2019

    • Author(s)
      Masayuki Hanyu, Hideki Ishii, Nobuki Nengaki, Masanao Ogawa, Daisuke Arashi, Kenji Furutsuka, Hiroki Hashimoto, Kazunori Kawamura, Ming-Rong Zhang
    • Organizer
      23nd International symposium on radiopharmaceutical science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Separation study of silver radionuclides from a palladium target irradiated by cyclotron2019

    • Author(s)
      Tomoyuki Ohya, Kotaro Nagatsu, Masayuki Hanyu, Katsuyuki Minegishi, Ming-Rong Zhang
    • Organizer
      23nd International symposium on radiopharmaceutical science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Develop a peptide-based PET radiotracer for imaging PD-L1 expression in cancer2019

    • Author(s)
      Kuan Hu, Lin Xie, Masayuki Hanyu, Yiding Zhang, Ming-Rong Zhang
    • Organizer
      23nd International symposium on radiopharmaceutical science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Peptide modified and radiometals loaded BP quantum dots for targeted PET imaging-guided tumor photothermal and photodynamic therapy2019

    • Author(s)
      Kuan Hu, Lin Xie, Masayuki Hanyu, Yiding Zhang, Ming-Rong Zhang
    • Organizer
      23nd International symposium on radiopharmaceutical science
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小分子放射性薬剤211At-AITMの合成と評価2018

    • Author(s)
      破入 正行, 謝 琳, 藤永 雅之, 張 一鼎, 羽鳥 晶子, 峯岸 克行, 李 惠子, 諸越 幸恵, 長谷川 純崇, 永津 弘太郎, 張 明栄
    • Organizer
      第58回日本核医学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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