Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis

Daisuke Asanuma; Yasuteru Urano; Tetsuo Nagano; Yukihiro Hama; Yoshinori Koyama; Hisataka Kobayashi

doi:10.1117/12.809938

20 February 2009 Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis

Daisuke Asanuma; Yasuteru Urano; Tetsuo Nagano; Yukihiro Hama; Yoshinori Koyama; Hisataka Kobayashi

Author Affiliations +

Proceedings Volume 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications; 71901A (2009) https://doi.org/10.1117/12.809938
Event: SPIE BiOS, 2009, San Jose, California, United States

Abstract

One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background. Here, we achieve specific in vivo tumor visualization with a newly-designed "activatable" targeted fluorescence probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the BODIPY fluorophore were synthesized, and then conjugated to a cancer-targeting monoclonal antibody, Trastuzumab, or galactosyl serum albumin (GSA). As proof of concept, ex and in vivo imaging of two different tumor mouse models was performed: HER2-overexpressed lung metastasis tumor with Trastuzumab-pH probe conjugates and lectin-overexpressed i.p. disseminated tumor with GSA-pH probe conjugates. These pH-activatable targeted probes were highly specific for tumors with minimal background signal. Because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. Furthermore, this strategy was also applied to fluorescence endoscopy in tumor mouse models, resulting in specific visualization of tumors as small as submillimeter in size that could hardly detected by naked eyes because of their poor contrast against normal tissues. The design concept can be widely adapted to cancer-specific cell-surface-targeting molecules that result in cellular internalization.

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Daisuke Asanuma, Daisuke Asanuma, Yasuteru Urano, Yasuteru Urano, Tetsuo Nagano, Tetsuo Nagano, Yukihiro Hama, Yukihiro Hama, Yoshinori Koyama, Yoshinori Koyama, Hisataka Kobayashi, Hisataka Kobayashi, } "Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis", Proc. SPIE 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications, 71901A (20 February 2009); doi: 10.1117/12.809938; https://doi.org/10.1117/12.809938

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