PET study of ocular and blood pharmacokinetics of intravitreal bevacizumab and aflibercept in rats

• Published in: European journal of pharmaceutics and biopharmaceutics 2020-09, Vol.154, p.330-337
• Main Authors: Luaces-Rodríguez, Andrea, del Amo, Eva M, Mondelo-García, Cristina, Gómez-Lado, Noemí, Gonzalez, Francisco, Ruibal, Álvaro, González-Barcia, Miguel, Zarra-Ferro, Irene, Otero-Espinar, Francisco J., Fernández-Ferreiro, Anxo, Aguiar, Pablo
• Format: Article
• Language: English
• Subjects: 89-Zirconium; Aflibercept; AMD; Anti-VEGF; Bevacizumab; Molecular imaging; PET; Pharmacokinetics
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2020.06.024

[Display omitted] Intravitreal injections are the standard procedure in the treatment of retinal pathologies, such as the administration of the anti-VEGF antibodies in age-related macular degeneration. The aim of this study is to evaluate the intraocular and blood pharmacokinetics after an intravitreal injection of 89Zr-labelled bevacizumab and 89Zr-labelled aflibercept in Sprague-Dawley rats using Positron Emission Tomography. First, both antibodies were radiolabelled to zirconium-89 with a maximum specific activity of 15 Mbq/mg for bevacizumab and 10 Mbq/mg for aflibercept. Four µL containing 1–1.2 Mq of 89Zr-labelled compound were injected into the vitreous through a 35 G needle. A microPET acquisition was carried out immediately after the injection and at different time points through a 12-day study and blood samples were obtained through the tail vein. Radiolabelling was successfully performed with a radiochemical purity after ultrafiltration above 95% for both agents. Both antibodies ocular curves followed a two-compartment model in which an intraocular elimination half-life of 16.44 h was found for 89Zr-bevacizumab and 4.51 h for 89Zr-aflibercept, considering the alpha phase as the elimination phase. Regarding the beta phase, a half-life of 3.23 days for 89Zr-bevacizumab and 4.69 days for 89Zr-aflibercept were observed. With regards to blood concentration, 89Zr-bevacizumab showed a blood half-life of 7.08 days, whereas 89Zr-aflibercept’s was 3.18 days, by a one-compartment model with first-order absorption kinetics. In conclusion, this study shows for the first time the ocular and blood pharmacokinetic analysis after intravitreal injection of aflibercept and bevacizumab in rats.