Research Papers: Imaging

Detection of enzyme activity in orthotopic murine breast cancer by fluorescence lifetime imaging using a fluorescence resonance energy transfer–based molecular probe

[+] Author Affiliations
Metasebya Solomon

Washington University, Department of Radiology, Optical Radiology Laboratory, 4525 Scott Avenue, St. Louis, Missouri 63110

Washington University, Department of Biomedical Engineering, 4525 Scott Avenue, St. Louis, Missouri 63110

Kevin Guo, Gail P. Sudlow, Mikhail Y. Berezin, W. Barry Edwards, Walter J. Akers

Washington University, Department of Radiology, Optical Radiology Laboratory, 4525 Scott Avenue, St. Louis, Missouri 63110

Samuel Achilefu

Washington University, Department of Radiology, Optical Radiology Laboratory, 4525 Scott Avenue, St. Louis, Missouri 63110

Washington University, Department of Biomedical Engineering, 4525 Scott Avenue, St. Louis, Missouri 63110

Washington University, Department of Biochemistry and Molecular Biophysics, 4525 Scott Avenue, St. Louis, Missouri 63110

J. Biomed. Opt. 16(6), 066019 (June 22, 2011). doi:10.1117/1.3594153
History: Received March 07, 2011; Revised April 22, 2011; Accepted May 04, 2011; Published June 22, 2011; Online June 22, 2011
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Cancer-related enzyme activity can be detected noninvasively using activatable fluorescent molecular probes. In contrast to “always-on” fluorescent molecular probes, activatable probes are relatively nonfluorescent at the time of administration due to intramolecular fluorescence resonance energy transfer (FRET). Enzyme-mediated hydrolysis of peptide linkers results in reduced FRET and increase of fluorescence yield. Separation of signal from active and inactive probe can be difficult with conventional intensity-based fluorescence imaging. Fluorescence lifetime (FLT) measurement is an alternative method to detect changes in FRET. Thus, we investigate FLT imaging for in vivo detection of FRET-based molecular probe activation in an orthotopic breast cancer model. Indeed, the measured FLT of the enzyme-activatable molecular probe increases from 0.62 ns just after injection to 0.78 ns in tumor tissue after 4 h. A significant increase in FLT is not observed for an always-on targeted molecular probe with the same fluorescent reporter. These results show that FLT contrast is a powerful addition to preclinical imaging because it can report molecular activity in vivo due to changes in FRET. Fluorescence lifetime imaging exploits unique characteristics of fluorescent molecular probes that can be further translated into clinical applications, including noninvasive detection of cancer-related enzyme activity.

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© 2011 Society of Photo-Optical Instrumentation Engineers (SPIE)

Citation

Metasebya Solomon ; Kevin Guo ; Gail P. Sudlow ; Mikhail Y. Berezin ; W. Barry Edwards, et al.
"Detection of enzyme activity in orthotopic murine breast cancer by fluorescence lifetime imaging using a fluorescence resonance energy transfer–based molecular probe", J. Biomed. Opt. 16(6), 066019 (June 22, 2011). ; http://dx.doi.org/10.1117/1.3594153


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