Intravitreal faricimab pharmacokinetics assessed by PET imaging in a neovascular Age-related Macular Degeneration rat model

Age-related Macular Degeneration (AMD) is the leading cause of blindness in the elderly, with its neovascular form characterised by abnormal vessel growth. Current anti-VEGF therapies require frequent intravitreal injections and show variable efficacy. Faricimab, a novel bispecific antibody targeting VEGF-A and ANG-2, offers a dual mechanism with the potential for enhanced efficacy and extended dosing intervals. This study aimed to characterise the intravitreal pharmacokinetics, biodistribution, and ocular localization of faricimab in a rat model of laser-induced choroidal neovascularization (CNV) using non-invasive molecular imaging. Faricimab was conjugated with DFO and radiolabelled with zirconium-89 ([ 89 Zr]Zr-DFO-faricimab), maintaining functional binding to VEGF-A and ANG-2. Following intravitreal injection, pharmacokinetics was assessed by PET/CT, blood sampling, and autoradiography, alongside structural retinal evaluation by OCT. Both healthy and CNV-induced rats demonstrated biphasic ocular clearance with similar half-lives, obtaining no significant differences (Control AUC ₀–∞ = 5587.3 ± 1419.3%·hour and AMD AUC ₀–∞ = 4079.1 ± 1178.6%·hour). Autoradiography confirmed predominant retention in the posterior segment, with AMD eyes showing higher early accumulation, suggesting altered diffusion, and increased retinal binding. Whole-body biodistribution revealed systemic uptake primarily in the liver and spleen, consistent with antibody catabolism. This work represents the first study to report pharmacokinetic data of faricimab as well as its intraocular distribution in an AMD model. Our findings support its therapeutic potential and highlight PET imaging as a powerful non-invasive tool for longitudinal ocular pharmacokinetic studies. • First non-invasive PK/PD study of faricimab using PET/CT in an animal model of CNV. • First report of faricimab intraocular distribution changes in healthy vs CNV eyes. • Validation of CNV model as a translational tool for studying intravitreal antibodies.