Noninvasive Imaging of Early Venous Thrombosis by 19F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions
Noninvasive Imaging of Early Venous Thrombosis by 19F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions
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DOI：
10.1161/circulationaha.114.010962
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发表时间：
2015-04-21
期刊：
影响因子：
37.8
通讯作者：
Floegel, Ulrich
中科院分区：
文献类型：
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作者：
Temme, Sebastian;Grapentin, Christoph;Floegel, Ulrich
背景：深静脉血栓和随后的肺血栓栓塞的无创检测是一个严重的医学挑战，因为这两种情况很难通过常规超声技术识别。方法和结果-在这里，我们报告了一种新的技术，用于敏感和特异性地识别发展中的血栓，使用无背景的F-19磁共振成像，以及α 2-抗纤溶蛋白肽（α 2(AP)）靶向全氟碳纳米乳（pfc）作为造影剂，它通过活性因子XIII与纤维蛋白交联。使用基于甾醇的插入后技术，通过温和的偶联条件确保配体的功能。血栓诱导后60分钟形成直径的血栓不再产生可检测到的F-19磁共振成像信号。在离体产生的人血块中获得了相应的结果。因此，α 2(AP)- pfc可以可视化新形成的血栓，这些血栓可能仍然容易受到药物干预。结论：我们的研究结果表明，H-1/F-19磁共振成像和α 2(AP)- pfc是一种敏感的、无创的诊断急性深静脉血栓和肺血栓栓塞的技术。此外，基于甾醇的插入后技术的配体偶联为pfc在体内F-19磁共振成像的特异性靶向提供了独特的平台。
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 F-19 magnetic resonance imaging, together with alpha 2-antiplasmin peptide (alpha 2(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 60 minutes after thrombus induction no longer resulted in detectable F-19 magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots. Thus, alpha 2(AP)-PFCs can visualize freshly developed thrombi that might still be susceptible to pharmacological intervention.Conclusions-Our results demonstrate that H-1/F-19 magnetic resonance imaging, together with alpha 2(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 F-19 magnetic resonance imaging.