Noninvasive Imaging of Early Venous Thrombosis by 19F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions. Issue 16 (21st April 2015)

• Record Type: Journal Article
• Authors: Temme, Sebastian; Grapentin, Christoph; Quast, Christine; Jacoby, Christoph; Grandoch, Maria; Ding, Zhaoping; Owenier, Christoph; Mayenfels, Friederike; Fischer, Jens W.; Schubert, Rolf; Schrader, Jürgen; Flögel, Ulrich
• Is Part Of: Circulation. Volume 131:Issue 16(2015)
• Publication Date: 2015-04-21
• Subjects: Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.114.010962
• Languages: English
• ISSNs: 0009-7322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>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.</p> </sec> <sec> <title>Methods and Results—</title> <p>Here, we report a novel technique for the sensitive and specific identification of developing thrombi using background-free <sup>19</sup>F magnetic resonance imaging, together with α2-antiplasmin peptide (α2<sup>AP</sup>)–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 <0.8 mm could be visualized unequivocally in the murine inferior vena cava as hot spots in vivo by simultaneous acquisition of anatomic matching <sup>1</sup>H and <sup>19</sup>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<sup>AP</sup>-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<sup>AP</sup>-PFCs >60 minutes after thrombus induction no longer resulted in detectable <sup>19</sup>F magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots. Thus, α2<sup>AP</sup>-PFCs can visualize freshly developed thrombi that might still be susceptible to pharmacological intervention.</p> </sec> <sec> <title>Conclusions—</title> <p>Our results demonstrate that <sup>1</sup>H/<sup>19</sup>F magnetic resonance imaging, together with α2<sup>AP</sup>-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 <sup>19</sup>F magnetic resonance imaging.</p> </sec> </abstract>