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Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo

Author

Listed:
  • Daisuke Asanuma

    (Graduate School of Medicine, The University of Tokyo
    Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Masayo Sakabe

    (Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Mako Kamiya

    (Graduate School of Medicine, The University of Tokyo
    PRESTO, Japan Science and Technology Agency)

  • Kyoko Yamamoto

    (Graduate School of Medicine, The University of Tokyo)

  • Jun Hiratake

    (Institute for Chemical Research, Kyoto University)

  • Mikako Ogawa

    (Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
    Present address: Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan)

  • Nobuyuki Kosaka

    (Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
    Present address: Faculty of Medical Science, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan)

  • Peter L. Choyke

    (Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health)

  • Tetsuo Nagano

    (Open Innovation Center for Drug Discovery, The University of Tokyo)

  • Hisataka Kobayashi

    (Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health)

  • Yasuteru Urano

    (Graduate School of Medicine, The University of Tokyo
    Graduate School of Pharmaceutical Sciences, The University of Tokyo
    CREST, Japan Science and Technology Agency
    Basic Research Program, Japan Science and Technology Agency)

Abstract

Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as

Suggested Citation

  • Daisuke Asanuma & Masayo Sakabe & Mako Kamiya & Kyoko Yamamoto & Jun Hiratake & Mikako Ogawa & Nobuyuki Kosaka & Peter L. Choyke & Tetsuo Nagano & Hisataka Kobayashi & Yasuteru Urano, 2015. "Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo," Nature Communications, Nature, vol. 6(1), pages 1-7, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7463
    DOI: 10.1038/ncomms7463
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