Albumin-Binding Domain Conjugate for Near-Infrared Fluorescence Lymphatic Imaging
Identifieur interne : 005141 ( Main/Merge ); précédent : 005140; suivant : 005142Albumin-Binding Domain Conjugate for Near-Infrared Fluorescence Lymphatic Imaging
Auteurs : Cynthia A. Davies-Venn [États-Unis] ; Bonnie Angermiller [États-Unis] ; Nathaniel Wilganowski [États-Unis] ; Pradip Ghosh [États-Unis] ; Barrett R. Harvey [États-Unis] ; Grace Wu [États-Unis] ; Sunkuk Kwon [États-Unis] ; Melissa B. Aldrich [États-Unis] ; Eva M. Sevick-Muraca [États-Unis]Source :
- Molecular Imaging and Biology [ 1536-1632 ] ; 2011.
Abstract
The aim of this study was to develop and characterize a novel peptide imaging agent for noninvasive near-infrared fluorescence imaging of protein transport by the lymphatics. An imaging agent consisting of a cyclic albumin-binding domain (cABD) peptide, with sequence, Arg-Leu-Ile-Glu-Asp-Ile-Cys-Leu-Pro-Arg-Trp-Gly-Cys-Leu-Trp-Glu-Asp-Asp-Lys, was conjugated to a near-infrared fluorophore, IRDye800CW, allowing for enhanced vascular uptake, retention, and fluorescence imaging.
Characterization of the cABD-IRDye800 peptide conjugate was performed using fluorescence spectroscopy to assess optical properties and SDS-PAGE and Biacore binding assays to determine binding affinity and specificity. Fluorescence imaging of normal C57BL/6 mice was conducted to monitor lymphatic uptake and retention.
cABD-IRDye800 exhibited approximately six times greater fluorescent yield and greater stability than indocyanine green, an agent previously used in humans to image lymphatic vasculature. The agent exhibited affinity for albumin with IC50 and Kd in the nanomolar range and demonstrated superior retention characteristics within mouse lymphatics when compared with IRDye800CW.
cABD-IRDye800 has utility for assessing lymphatic function in mouse models of human lymphatic disease and the potential for use in clinical diagnostic imaging of the lymphatic vasculature.
The online version of this article (doi:10.1007/s11307-011-0499-x) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1007/s11307-011-0499-x
PubMed: 21688052
PubMed Central: 3346932
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Davies-Venn</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff3">Translational Biology and Molecular Medicine Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Translational Biology and Molecular Medicine Program, Baylor College of Medicine, One Baylor Plaza, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Angermiller, Bonnie" sort="Angermiller, Bonnie" uniqKey="Angermiller B" first="Bonnie" last="Angermiller">Bonnie Angermiller</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Wilganowski, Nathaniel" sort="Wilganowski, Nathaniel" uniqKey="Wilganowski N" first="Nathaniel" last="Wilganowski">Nathaniel Wilganowski</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Ghosh, Pradip" sort="Ghosh, Pradip" uniqKey="Ghosh P" first="Pradip" last="Ghosh">Pradip Ghosh</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Harvey, Barrett R" sort="Harvey, Barrett R" uniqKey="Harvey B" first="Barrett R." last="Harvey">Barrett R. Harvey</name><affiliation wicri:level="2"><nlm:aff id="Aff2">The Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler St. SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler St. SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Wu, Grace" sort="Wu, Grace" uniqKey="Wu G" first="Grace" last="Wu">Grace Wu</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Kwon, Sunkuk" sort="Kwon, Sunkuk" uniqKey="Kwon S" first="Sunkuk" last="Kwon">Sunkuk Kwon</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Aldrich, Melissa B" sort="Aldrich, Melissa B" uniqKey="Aldrich M" first="Melissa B." last="Aldrich">Melissa B. Aldrich</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author><author><name sortKey="Sevick Muraca, Eva M" sort="Sevick Muraca, Eva M" uniqKey="Sevick Muraca E" first="Eva M." last="Sevick-Muraca">Eva M. Sevick-Muraca</name><affiliation wicri:level="2"><nlm:aff id="Aff1">The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, SRB 330A, Houston</wicri:cityArea></affiliation></author></analytic><series><title level="j">Molecular Imaging and Biology</title><idno type="ISSN">1536-1632</idno><idno type="eISSN">1860-2002</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>The aim of this study was to develop and characterize a novel peptide imaging agent for noninvasive near-infrared fluorescence imaging of protein transport by the lymphatics. An imaging agent consisting of a cyclic albumin-binding domain (cABD) peptide, with sequence, Arg-Leu-Ile-Glu-Asp-Ile-Cys-Leu-Pro-Arg-Trp-Gly-Cys-Leu-Trp-Glu-Asp-Asp-Lys, was conjugated to a near-infrared fluorophore, IRDye800CW, allowing for enhanced vascular uptake, retention, and fluorescence imaging.</p></sec><sec><title>Procedure</title><p>Characterization of the cABD-IRDye800 peptide conjugate was performed using fluorescence spectroscopy to assess optical properties and SDS-PAGE and Biacore binding assays to determine binding affinity and specificity. Fluorescence imaging of normal C57BL/6 mice was conducted to monitor lymphatic uptake and retention.</p></sec><sec><title>Results</title><p>cABD-IRDye800 exhibited approximately six times greater fluorescent yield and greater stability than indocyanine green, an agent previously used in humans to image lymphatic vasculature. The agent exhibited affinity for albumin with IC<sub>50</sub> and Kd in the nanomolar range and demonstrated superior retention characteristics within mouse lymphatics when compared with IRDye800CW.</p></sec><sec><title>Conclusions</title><p>cABD-IRDye800 has utility for assessing lymphatic function in mouse models of human lymphatic disease and the potential for use in clinical diagnostic imaging of the lymphatic vasculature.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s11307-011-0499-x) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Rockson, Sg" uniqKey="Rockson S">SG Rockson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author><author><name sortKey="Tammela, T" uniqKey="Tammela T">T 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