Research Papers: Imaging

In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium

[+] Author Affiliations
Craig J. Goergen, Anand T. N. Kumar

Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129

Howard H. Chen

Harvard Medical School, Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129

Alexei Bogdanov

University of Massachusetts Medical School, Laboratory of Molecular Imaging Probes, Department of Radiology, 55 Lake Avenue North, Worcester, Massachusetts 01605

David E. Sosnovik

Harvard Medical School, Athinoula A Martinos Center for Biomedical Imaging and Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129

J. Biomed. Opt. 17(5), 056001 (Apr 20, 2012). doi:10.1117/1.JBO.17.5.056001
History: Received January 6, 2012; Revised March 2, 2012; Accepted March 5, 2012
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Abstract.  Activatable fluorescent molecular probes are predominantly nonfluorescent in their inactivated state due to intramolecular quenching, but increase fluorescence yield significantly after enzyme-mediated hydrolysis of peptides. Continuous wave in vivo detection of these protease-activatable fluorophores in the heart, however, is limited by the inability to differentiate between activated and nonactivated fractions of the probe and is frequently complicated by large background signal from probe accumulation in the liver. Using a cathepsin-activatable near-infrared probe (PGC-800), we demonstrate here that fluorescence lifetime (FL) significantly increases in infarcted murine myocardial tissue (0.67 ns) when compared with healthy myocardium (0.59 ns) after 24 h. Furthermore, we show that lifetime contrast can be used to distinguish in vivo cardiac fluorescence from background nonspecific liver signal. The results of this study show that lifetime contrast is a helpful addition to preclinical imaging of activatable fluorophores in the myocardium by reporting molecular activity in vivo due to changes in intramolecular quenching. This characterization of FL from activatable molecular probes will be helpful for advancing in vivo imaging of enzyme activity.

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© 2012 Society of Photo-Optical Instrumentation Engineers

Citation

Craig J. Goergen ; Howard H. Chen ; Alexei Bogdanov, Jr. ; David E. Sosnovik and Anand T. N. Kumar
"In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium", J. Biomed. Opt. 17(5), 056001 (Apr 20, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.5.056001


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