Ocular Biodistribution Of Zr-89-Bevacizumab In New Zealand Rabbits Determined Using Pet/Mri: A Feasibility Study

Background: Despite studies on positron emission tomography/magnetic resonance imaging (PET/MRI) in oncological imaging with high soft-tissue contrast resolution, PET/MRI has not been studied in ophthalmology. Zr-89-bevacizumab, designed as a probe for PET, targets vascular endothelial growth factor, which is highly expressed in ocular angiogenesis. Intravitreal injections of bevacizumab agents have curative effects on ocular disease.Objectives: To study the ocular biodistribution of Zr-89-bevacizumab in New Zealand rabbits using PET/MRI.Materials and Methods: Zr-89-bevacizumab, synthesized from conjugated bevacizumab and Zr-89-oxalate, and the purity of radio-labeled antibodies were determined using radio high-performance liquid chromatography (radio-HPLC). Instant thin-layer chromatography (ITLC) was utilized to differentiate the labeled product from aggregates and unlabeled Zr-89. Zr-89-bevacizumab was injected 2 mm from the left limbus into the vitreous humor of six normal New Zealand white rabbits. Micro-PET was utilized for dynamic imaging from 5 minutes to 60 minutes postinjection and for static imaging at 4 hours, 24 hours, 48 hours,120 hours, and 144 hours (10-minutes scans) postinjection. PET/MRI scans were fused using PMOD software.Results: Zr-89-bevacizumab with a radiochemical purity of 93.21% was monitored via PET imaging. Radioactivity levels in the eyes plateaued approximately 5 minutes after administration of Zr-89-bevacizumab, and the measured vitreous values decreased from 340.52 +/- 41.6% injected dose (ID)/g to 21.53 +/- 3.39%ID/g by 144 hours. The half-life of the drug in the eye was calculated for 84.25 hours.Conclusion: Zr-89-bevacizumab could be monitored in animals by PET imaging, and the radiolabel exhibited high sensitivity in the vitreous body. Radioactivity levels in the eyes plateaued approximately 5 minutes after administration. This study clearly demonstrates the biodistribution of Zr-89-bevacizumab.