Jacoby Christoph, Temme Sebastian, Mayenfels Friederike, Benoit Nicole, Krafft Marie Pierre, Schubert Rolf, Schrader Jürgen, Flögel Ulrich
Institut für Molekulare Kardiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
NMR Biomed. 2014 Mar;27(3):261-71. doi: 10.1002/nbm.3059. Epub 2013 Dec 19.
Inflammatory processes can reliably be assessed by (19)F MRI using perfluorocarbons (PFCs), which is primarily based on the efficient uptake of emulsified PFCs by circulating cells of the monocyte-macrophage system and subsequent infiltration of the (19)F-labeled cells into affected tissue. An ideal candidate for the sensitive detection of fluorine-loaded cells is the biochemically inert perfluoro-15-crown-5 ether (PFCE), as it contains 20 magnetically equivalent (19)F atoms. However, the biological half-life of PFCE in the liver and spleen is extremely long, and so this substance is not suitable for future clinical applications. In the present study, we investigated alternative, nontoxic PFCs with predicted short biological half-lives and high fluorine content: perfluorooctyl bromide (PFOB), perfluorodecalin (PFD) and trans-bis-perfluorobutyl ethylene (F-44E). Despite the complex spectra of these compounds, we obtained artifact-free images using sine-squared acquisition-weighted three-dimensional chemical shift imaging and dedicated reconstruction accomplished with in-house-developed software. The signal-to-noise ratio of the images was maximized using a Nutall window with only moderate localization error. Using this approach, the retention times of the different PFCs in murine liver and spleen were determined at 9.4 T. The biological half-lives were estimated to be 9 days (PFD), 12 days (PFOB) and 28 days (F-44E), compared with more than 250 days for PFCE. In vivo sensitivity for inflammation imaging was assessed using an ear clip injury model. The alternative PFCs PFOB and F-44E provided 37% and 43%, respectively, of the PFCE intensities, whereas PFD did not show any signal in the ear model. Thus, for in vivo monitoring of inflammatory processes, PFOB emerges as the most promising candidate for possible future translation of (19)F MR inflammation imaging to human applications.
炎症过程可以通过使用全氟化碳（PFC）的（19）F磁共振成像（MRI）可靠地评估，这主要基于单核巨噬细胞系统的循环细胞对乳化PFC的有效摄取，以及随后（19）F标记的细胞浸润到受影响的组织中。用于灵敏检测氟负载细胞的理想候选物是生物化学惰性的全氟-15-冠-5醚（PFCE），因为它含有20个磁等价的（19）F原子。然而，PFCE在肝脏和脾脏中的生物半衰期极长，因此这种物质不适合未来的临床应用。在本研究中，我们研究了具有预测的短生物半衰期和高氟含量的替代无毒PFC：全氟辛基溴（PFOB）、全氟萘烷（PFD）和反式双全氟丁基乙烯（F-44E）。尽管这些化合物的光谱复杂，但我们使用正弦平方采集加权三维化学位移成像和用自行开发的软件完成的专用重建获得了无伪影图像。使用仅具有中等定位误差的努塔尔窗使图像的信噪比最大化。使用这种方法，在9.4T下测定了不同PFC在小鼠肝脏和脾脏中的保留时间。估计生物半衰期分别为9天（PFD）、12天（PFOB）和28天（F-44E），而PFCE超过250天。使用耳夹损伤模型评估炎症成像的体内敏感性。替代PFCs PFOB和F-44E分别提供了PFCE强度的37%和43%，而PFD在耳部模型中未显示任何信号。因此，对于炎症过程的体内监测，PFOB成为未来将（19）F MR炎症成像转化为人类应用的最有前景的候选物。
