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Proceedings Paper

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

Paper Details

Date Published: 20 February 2009
PDF: 10 pages
Proc. SPIE 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications, 71901A (20 February 2009); doi: 10.1117/12.809938
Show Author Affiliations
Daisuke Asanuma, The Univ. of Tokyo (Japan)
CREST/JSPS, Japan Science and Technology Agency (Japan)
Yasuteru Urano, The Univ. of Tokyo (Japan)
PRESTO, Japan Science and Technology Agency (Japan)
Tetsuo Nagano, The Univ. of Tokyo (Japan)
CREST, Japan Science and Technology Agency (Japan)
Yukihiro Hama, National Institutes of Health (United States)
Yoshinori Koyama, National Institutes of Health (United States)
Hisataka Kobayashi, National Institutes of Health (United States)

Published in SPIE Proceedings Vol. 7190:
Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications
Samuel Achilefu; Ramesh Raghavachari, Editor(s)

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