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

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    Authors
    Goergen, Craig J.
    Chen, Howard H.
    Bogdanov, Alexei A. Jr.
    Sosnovik, David E.
    Kumar, Anand T. N.
    UMass Chan Affiliations
    Department of Radiology
    Document Type
    Journal Article
    Publication Date
    2012-05-23
    Keywords
    Animals
    Biological Markers
    Cathepsins
    Mice
    Mice, Inbred C57BL
    Microscopy, Fluorescence
    Molecular Imaging
    Molecular Probe Techniques
    Myocardial Infarction
    Polymers
    Spectrometry, Fluorescence
    Amino Acids, Peptides, and Proteins
    Cardiovascular System
    Chemistry
    Diagnosis
    Investigative Techniques
    Radiology
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381023/pdf/JBO-017-056001.pdf
    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.
    Source
    J Biomed Opt. 2012 May;17(5):056001. doi: 10.1117/1.JBO.17.5.056001. Link to article on publisher's site
    DOI
    10.1117/1.JBO.17.5.056001
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48600
    PubMed ID
    22612124
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1117/1.JBO.17.5.056001
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