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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/627123 |
| Date | 01 November 2017 |
| Creators | Christoforidis, John Byron, Briley, Karen, Binzel, Katherine, Bhatia, Prayna, Wei, Lai, Kumar, Krishan, Knopp, Michael Vinzenz |
| Contributors | Univ Arizona, Med Ctr, Dept Ophthalmol & Vis Sci, Department of Ophthalmology & Vision Science, University of Arizona Medical Center, Tucson, Arizona, United States 2Retina Specialists of Southern Arizona, Tucson, Arizona, United States, Department of Radiology, College of Medicine, The Ohio State University, Columbus, Ohio, United States, Department of Radiology, College of Medicine, The Ohio State University, Columbus, Ohio, United States, Department of Radiology, College of Medicine, The Ohio State University, Columbus, Ohio, United States, Center for Biostatistics, College of Medicine, The Ohio State University, Columbus, Ohio, United States, Department of Radiology, College of Medicine, The Ohio State University, Columbus, Ohio, United States, Department of Radiology, College of Medicine, The Ohio State University, Columbus, Ohio, United States |
| Publisher | ASSOC RESEARCH VISION OPHTHALMOLOGY INC |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | Copyright © 2017 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
| Relation | http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.17-22431 |
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