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. 89 Zr-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 89 Zr-bevacizumab in New Zealand rabbits using PET/MRI. Materials and Methods: 89 Zr-bevacizumab, synthesized from conjugated bevacizumab and 89 Zr-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 89 Zr. 89 Zr-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: 89 Zr-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 89 Zr-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:89 Zr-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 89 Zr-bevacizumab.
ObjectiveIntravenous tissue plasminogen activator (tPA) is the standard therapy for patients with acute ischaemic stroke (AIS) within 4.5 hours of onset. Recent trials have expanded the endovascular treatment window to 24 hours. We investigated the efficacy and safety of using multimodal MRI to guide intravenous tPA treatment for patients with AIS of unknown time of onset (UTO).MethodsData on patients with AIS with UTO and within 4.5 hours of onset were reviewed. Data elements collected and analysed included: demographics, National Institutes of Health Stroke Scale (NIHSS) score at baseline and 2 hours, 24 hours, 7 days after thrombolysis and before discharge, the modified Rankin Scale (mRS) score at 3 months after discharge, imaging findings and any adverse event.ResultsForty-two patients with UTO and 62 in control group treated within 4.5 hours of onset were treated with intravenous tPA. The NIHSS scores after thrombolysis and/or before discharge in UTO group were significantly improved compared with the baseline (p<0.05). Between the two groups, no significant differences in NIHSS score were observed (p>0.05). Utilising the non-inferiority test, to compare mRS scores (0–2) at 3 months between the two groups, the difference was 5.2% (92% CI, OR 0.196). Patients in the UTO group had mRS scores of 0-2, which were non-inferior to the control group. Their incidence of adverse events was similar.ConclusionsUtilising multimodal MRI to guide intravenous only thrombolysis for patients with AIS with UTO was safe and effective. In those patients with AIS between 6 and 24 hours of time of onset but without large arterial occlusion, intravenous thrombolysis could be considered an option.
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