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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.
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