Ocular Biodistribution of 89Zr-Bevacizumab in New Zealand Rabbits Determined Using PET/MRI: A Feasibility Study

• Published in: Iranian journal of radiology Vol. In Press; no. In Press
• Main Authors: Liu, Xiaoyuan, Ye, Jianqiang, Zhang, Yan, Liu, Quan, Bai, Ruizhen, Yuan, Wenbo, Cai, Dongyan, Zheng, Xiaoyuan, Bian, Yun, Zhou, Shijun, Lv, Juan, Ding, Yongjuan, Xie, Fen, Lu, Hongwen, Xie, Bingxue
• Format: Journal Article
• Language: English
• Published: Tehran Tehran University of Medical Sciences 01.04.2019
• Subjects: Antibodies; Cancer therapies; Chromatography; Diabetes; Diabetic retinopathy; Emission analysis; Eye diseases; Feasibility studies; Growth factors; High performance liquid chromatography; Immunotherapy; Labeling; Laboratory animals; Macular degeneration; Magnetic resonance imaging; Medical imaging; Monoclonal antibodies; Ophthalmology; Positron emission; Purity; Quality control; Rabbits; Radioactivity; Radiochemistry; Targeted cancer therapy; Thin layer chromatography; Tomography; Vascular endothelial growth factor; Vitreous humour; Zirconium isotopes; New Zealand
• ISSN: 1735-1065; 2008-2711
• DOI: 10.5812/iranjradiol.68697

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. 89Zr-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 89Zr-bevacizumab in New Zealand rabbits using PET/MRI. Materials and Methods: 89Zr-bevacizumab, synthesized from conjugated bevacizumab and 89Zr-oxalate, and the purity of radiolabeled 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 89Zr. 89Zr-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: 89Zr-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 89Zr-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: 89Zr-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 89Zr-bevacizumab.