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John Christoforidis, Karen Briley, Prayna Bhatia, Krishan Kumar, Michael V. Knopp; Intravitreal pharmacokinetic properties and systemic biodistribution characteristics of I-124 labeled bevacizumab, ranibizumab and aflibercept with PET/CT imaging on a non-human primate model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):221. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of I-124 labeled bevacizumab, ranibizumab and aflibercept with PET/CT imaging on a non-human primate model.
Each agent was radiolabeled with I-124 using a modified Iodogen method. The right eye of each of 3 owl monkeys underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, 0.5 mg/0.05 mL I-124 ranibizumab or 2.0 mg/0.05 mL I-124 aflibercept. All subjects were imaged using digital PET/CT scanner (Philips, Philips Healthcare) on days 0,1,2,4,8,14,21,28, and 35. Serum blood draws were performed on 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 non-ocular organs.
The intravitreal half-lives were 3.46 days for I-124 bevacizumab, 2.89 days for I-124 ranibizumab and 3.08 days for I-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 significant amounts in the liver, heart and distal bone. There was no uptake in the brain for any of the 3 agents.
Among the 3 anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and ranibizumab the shortest. Higher and prolonged levels of bevacizumab were found in the serum as well as the heart, liver and distal bone. These differences in organ biodistribution and retention times between the three drug agents should be taken into account during clinical decision-making in the course of intravitreal anti-VEGF therapy. Future studies with greater number of subjects is recommended.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Digital PET/CT Images captured with Philips Vereos scanner demonstrating intravitreal I-124 ranibizumab (color, left) and systemic biodistribution (B/W, right) 1 day after intravitreal injection of the right eye.
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