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

Daisuke Asanuma, Masayo Sakabe, Mako Kamiya, Kyoko Yamamoto, Jun Hiratake, Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Tetsuo Nagano, Hisataka Kobayashi and Yasuteru Urano ()
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Daisuke Asanuma: Graduate School of Medicine, 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
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
Nobuyuki Kosaka: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
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

Nature Communications, 2015, vol. 6, issue 1, 1-7

Abstract: 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

Date: 2015
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DOI: 10.1038/ncomms7463

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