Dabigatran, directly targeting thrombin, is widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF). We reported a rare case of left atrial appendage thrombus formation in a persistent NVAF patient despite the 31 months uninterrupted treatment with dabigatran 110 mg twice daily. The patient is a carrier of ABCB1 variant alleles with 7 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167) as well as CES-1 variant alleles with 2 homozygote SNPs (rs2244613 and rs4122238) and 2 heterozygote SNPs (rs8192935 and rs4580160), which may contribute to the changes of dabigatran plasma concentration. In addition, Drug-drug interaction with atorvastatin may also play a role to decrease dabigatran plasma concentration. There are only four such cases till date, of which had thrombus in the left atrium, reported in the literature. We firstly reported the documented case in a Chinese patient carrying multiple alleles of ABCB1 and CES-1, who suffered from thrombus in the left atrial appendage despite long-term anticoagulation with dabigatran. More clinical data are required to elucidate the impact of CES-1 and ABCB1 polymorphism on dabigatran pharmacokinetics, especially for Asian.

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.