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Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes.


ABSTRACT: A long-term goal of cancer diagnosis is to develop tumor-imaging techniques that have sufficient specificity and sensitivity. To achieve this goal, minimizing the background signal originating from nontarget tissues is crucial. Here we achieve highly specific in vivo cancer visualization by using a newly designed targeted 'activatable' fluorescent imaging probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the boron-dipyrromethene fluorophore were synthesized and then conjugated to a cancer-targeting monoclonal antibody. As proof of concept, ex vivo and in vivo imaging of human epidermal growth factor receptor type 2-positive lung cancer cells in mice was performed. The probe was highly specific for tumors with minimal background signal. Furthermore, because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. The design concept can be widely adapted to cancer-specific, cell surface-targeting molecules that result in cellular internalization.

SUBMITTER: Urano Y 

PROVIDER: S-EPMC2790281 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes.

Urano Yasuteru Y   Asanuma Daisuke D   Hama Yukihiro Y   Koyama Yoshinori Y   Barrett Tristan T   Kamiya Mako M   Nagano Tetsuo T   Watanabe Toshiaki T   Hasegawa Akira A   Choyke Peter L PL   Kobayashi Hisataka H  

Nature medicine 20081207 1


A long-term goal of cancer diagnosis is to develop tumor-imaging techniques that have sufficient specificity and sensitivity. To achieve this goal, minimizing the background signal originating from nontarget tissues is crucial. Here we achieve highly specific in vivo cancer visualization by using a newly designed targeted 'activatable' fluorescent imaging probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes bas  ...[more]

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