title: Detection of enzyme activity in orthotopic murine breast cancer by fluorescence lifetime imaging using a fluorescence resonance energy transfer-based molecular probe.
abstract: 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.
authors: Washington University, Department of Radiology, Optical Radiology Laboratory, 4525 Scott Avenue, St. Louis, Missouri 63110, USA.
authors: Metasebya
authors: M
authors: Solomon
authors: Kevin
authors: K
authors: Guo
authors: Gail P
authors: GP
authors: Sudlow
authors: Mikhail Y
authors: MY
authors: Berezin
authors: W Barry
authors: WB
authors: Edwards
authors: Samuel
authors: S
authors: Achilefu
authors: Walter J
authors: WJ
authors: Akers
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016018:Least-Squares Analysis; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3