1. Noninvasive Imaging of Early Venous Thrombosis by 19F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions
- Author
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Ulrich Flögel, Christoph Grapentin, Jens W. Fischer, Christoph Owenier, Christoph Jacoby, Friederike Mayenfels, Rolf Schubert, Sebastian Temme, Jürgen Schrader, Maria Grandoch, Christine Quast, and Zhaoping Ding
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Contrast Media ,Vena Cava, Inferior ,Signal-To-Noise Ratio ,Inferior vena cava ,Sensitivity and Specificity ,Fibrin ,Monocytes ,Polyethylene Glycols ,Fluorine-19 Magnetic Resonance Imaging ,Mice ,In vivo ,Physiology (medical) ,medicine ,Animals ,Humans ,Tissue Distribution ,Venous Thrombosis ,Drug Carriers ,Fluorocarbons ,alpha-2-Antiplasmin ,biology ,medicine.diagnostic_test ,business.industry ,Macrophages ,Magnetic resonance imaging ,Fluorine ,medicine.disease ,Factor XIII ,Pulmonary embolism ,Mice, Inbred C57BL ,Venous thrombosis ,Cholesterol ,Early Diagnosis ,medicine.vein ,biology.protein ,Emulsions ,Molecular imaging ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Factor XIIIa ,Pulmonary Embolism ,Nanospheres ,medicine.drug - Abstract
Background— Noninvasive detection of deep venous thrombi and subsequent pulmonary thromboembolism is a serious medical challenge, since both incidences are difficult to identify by conventional ultrasound techniques. Methods and Results— Here, we report a novel technique for the sensitive and specific identification of developing thrombi using background-free 19 F magnetic resonance imaging, together with α2-antiplasmin peptide (α2 AP )–targeted perfluorocarbon nanoemulsions (PFCs) as contrast agent, which is cross-linked to fibrin by active factor XIII. Ligand functionality was ensured by mild coupling conditions using the sterol-based postinsertion technique. Developing thrombi with a diameter 1 H and 19 F magnetic resonance images at 9.4 T with both excellent signal-to-noise and contrast-to-noise ratios (71±22 and 17±5, respectively). Furthermore, α2 AP -PFCs could be successfully applied for the diagnosis of experimentally induced pulmonary thromboembolism. In line with the reported half-life of factor XIIIa, application of α2 AP -PFCs >60 minutes after thrombus induction no longer resulted in detectable 19 F magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots. Thus, α2 AP -PFCs can visualize freshly developed thrombi that might still be susceptible to pharmacological intervention. Conclusions— Our results demonstrate that 1 H/ 19 F magnetic resonance imaging, together with α2 AP -PFCs, is a sensitive, noninvasive technique for the diagnosis of acute deep venous thrombi and pulmonary thromboemboli. Furthermore, ligand coupling by the sterol-based postinsertion technique represents a unique platform for the specific targeting of PFCs for in vivo 19 F magnetic resonance imaging.
- Published
- 2014