Time-domain imaging with quench-based fluorescent contrast agents

Walter J. Akers, Metasebya Solomon, Gail P. Sudlow, Mikhail Berezin, Samuel Achilefu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration, fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging for detecting activation of quench-based probes. Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration, fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging for detecting activation of quench-based probes. Time-domain diffuse optical imaging was performed to assess the FRET and quenching in living mice with orthotopic breast cancer. Tumor contrast enhancement was accompanied by increased fluorescence lifetime after administration of quenched probes selective for matrix metalloproteinases while no significant change was observed for non-quenched probes for integrin receptors. These results demonstrate the utility of timedomain imaging for detection of cancer-related enzyme activity in vivo.

Original languageEnglish
Title of host publicationReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV
DOIs
StatePublished - Apr 16 2012
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV - San Francisco, CA, United States
Duration: Jan 23 2012Jan 25 2012

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume8233
ISSN (Print)1605-7422

Conference

ConferenceReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV
CountryUnited States
CitySan Francisco, CA
Period01/23/1201/25/12

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  • Cite this

    Akers, W. J., Solomon, M., Sudlow, G. P., Berezin, M., & Achilefu, S. (2012). Time-domain imaging with quench-based fluorescent contrast agents. In Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV [82330G] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 8233). https://doi.org/10.1117/12.915917