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Rapid Visualization of Deeply Located Tumors In Vivo by Intravenous Administration of a γ-Glutamyltranspeptidase-Activated Fluorescent Probe

  • Akihiro Nakada
    Akihiro Nakada
    DMPK Research Laboratory, Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Company, Limited, 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
  • Takuma Maruyama
    Takuma Maruyama
    Toxicology Research Laboratory, Watarase Research Center, Discovery Research Headquarters, Kyorin Pharmaceutical Company, Limited, 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
  • Mako Kamiya
    Mako Kamiya
    Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    More by Mako Kamiya
  • Kenjiro Hanaoka
    Kenjiro Hanaoka
    Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
  • , and 
  • Yasuteru Urano*
    Yasuteru Urano
    Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
    *Email: [email protected]. Phone: (+81)358413601. Fax: (+81)358413563.
Cite this: Bioconjugate Chem. 2022, 33, 3, 523–529
Publication Date (Web):February 15, 2022
https://doi.org/10.1021/acs.bioconjchem.2c00039
Copyright © 2022 American Chemical Society

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    Abstract

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    We previously showed that spraying the fluorescent probe gGlu-HMRG (γ-glutamyl hydroxymethyl rhodamine green) can visualize even tiny tumors on the mesentery and peritoneal wall of tumor-bearing mice. However, during surgery, repeated spraying is necessary to detect tumors located deep within organs. Here, we examine whether deeply located tumors can be stained by intravenous administration of this probe. In mice bearing subcutaneous tumors, intravenous administration of gGlu-HMRG resulted in a rapid and specific increase of fluorescence in the tumor, which was visible to the naked eye within 5 min, and the maximum fluorescence intensity ratio of tumor to normal tissue (T/N = 4.3) was reached at 30 min. In mice bearing lung tumors, the T/N ratio reached approximately 20 at 30 min after administration, and deeply located tumors were clearly visualized. These results suggest that intravenous administration of gGlu-HMRG may be a useful technique in fluorescence-guided surgery of tumors.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.bioconjchem.2c00039.

    • Additional fluorescence imaging data and result of toxicology study (PDF)

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    Cited By

    This article is cited by 3 publications.

    1. Yiming Zhang, Zexi Zhang, Miaomiao Wu, Run Zhang. Advances and Perspectives of Responsive Probes for Measuring γ-Glutamyl Transpeptidase. ACS Measurement Science Au 2024, 4 (1) , 54-75. https://doi.org/10.1021/acsmeasuresciau.3c00045
    2. Qian Liu, Jie Yuan, Renfeng Jiang, Longwei He, Xuefeng Yang, Lin Yuan, Dan Cheng. γ-Glutamyltransferase-Activatable Fluoro-Photoacoustic Reporter for Highly Sensitive Diagnosis of Acute Liver Injury and Tumor. Analytical Chemistry 2023, 95 (3) , 2062-2070. https://doi.org/10.1021/acs.analchem.2c04894
    3. Kaijie Ren, Xin Xie, Tianhao Min, Tuanhe Sun, Haonan Wang, Yong Zhang, Chengxue Dang, Hao Zhang. Development of the Peritoneal Metastasis: A Review of Back-Grounds, Mechanisms, Treatments and Prospects. Journal of Clinical Medicine 2023, 12 (1) , 103. https://doi.org/10.3390/jcm12010103

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