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John Byron Christoforidis, Michelle Williams, Frank M Epitropoulos, Michael V. Knopp; Anatomic and pharmacokinetic properties of bevacizumab, ranibizumab and aflibercept following intravitreal injection in a rabbit model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1523.
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© ARVO (1962-2015); The Authors (2016-present)
To determine and compare the anatomic characteristics and pharmacokinetic properties of intravitreally-placed I-124-labeled bevacizumab (Avastin®, Roche Laboratories, Basel, Switzerland), ranibizumab (Lucentis®, Roche Laboratories, Basel, Switzerland) and aflibercept (Eyelea®, Regeneron, Tarrytown, NY, USA) in a rabbit model.
Each agent was radiolabeled with I-124 using a modified Iodogen method. Intravitreal injections were performed with a 32 gauge needle in the left eye of each subject. Three anesthetized Dutch-belted rabbits underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, three with 0.5 mg/0.05 mL I-124 ranibizumab and four with 2.0 mg/0.05 mL I-124 aflibercept. Serial imaging with micro PET-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) were obtained on days 0, 2, 5, 7, 14, 21, 28 and 35. Radioactive emission was measured in becquerels/mL (Bq/mL) and modified with a correction factor to account for I-124 radioactive decay. These values were then used to calculate the radioactive agent half-life for each subject.
All three labeled agents were contained within the vitreous cavity for the duration of the study with no extravasation into the central nervous system or elsewhere. On day 0, subconjunctival blebs could be seen in 5/10 subjects. The individual decay curves were consistent within each of the three agents. The average clearance half-lives with standard errors after correction for radioactive decay were 4.22 ± 0.12 days for I-124 bevacizumab, 2.81 ± 0.08 days for I-124 ranibizumab and 4.58 ± 0.07 days for I-124 aflibercept. Phantoms in syringes were clearly visible at day 28 for I-124 ranibizumab and day 35 for I-124 bevacizumab and I-124 aflibercept.
There was no significant escape from the vitreous cavity for the 3 agents. The appearance of a subconjunctival bleb on PET/CT following intravitreal injection of a labeled drug would indicate the presence of drug rather than vitreous within the bleb. Aflibercept demonstrated the longest intravitreal retention time and ranibizumab the shortest. These differences in retention times between the three drug agents may be taken into account during clinical decision-making in the course of intravitreal anti-VEGF therapy.
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