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    Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model

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    Author
    Christoforidis, John Byron
    Briley, Karen
    Binzel, Katherine
    Bhatia, Prayna
    Wei, Lai
    Kumar, Krishan
    Knopp, Michael Vinzenz
    Affiliation
    Univ Arizona, Med Ctr, Dept Ophthalmol & Vis Sci
    Issue Date
    2017-11-01
    Keywords
    biodistribution
    pharmacokinetics
    radiolabeling
    positron emission tomography
    intravitreal drug delivery
    
    Metadata
    Show full item record
    Publisher
    ASSOC RESEARCH VISION OPHTHALMOLOGY INC
    Citation
    Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model 2017, 58 (13):5636 Investigative Opthalmology & Visual Science
    Journal
    Investigative Opthalmology & Visual Science
    Rights
    Copyright © 2017 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    PURPOSE. To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of 1-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. METHODS. Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL 1-124 bevacizumab, 0.5 mg/0.05 mL 1-124 ranibizumab, or 2.0 mg/0.05 mL 1-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. RESULTS. The intravitreal half-lives were 3.60 days for 1-124 bevacizumab, 2.73 days for 1-124 ranibizumab, and 2.44 days for 1-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. CONCLUSIONS. Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.
    Note
    Open access journal.
    ISSN
    1552-5783
    DOI
    10.1167/iovs.17-22431
    Version
    Final published version
    Sponsors
    Macular Degeneration Research Fund from the Department of Ophthalmology & Vision Science, University of Arizona Medical Center and Lions Clubs International
    Additional Links
    http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.17-22431
    ae974a485f413a2113503eed53cd6c53
    10.1167/iovs.17-22431
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