Biomedical 19F MRI Using Perfluorocarbons

  • Tuba Güden-Silber
  • Sebastian Temme
  • Christoph Jacoby
  • Ulrich Flögel
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1718)

Abstract

Background-free fluorine (19F) MR imaging exhibits an excellent degree of specificity, and facilitates among others the in vivo visualization of inflammatory processes. Merging19F MR images with morphologically matching1H MR images enables the exact anatomic localization of the observed19F signal. Biochemically inert nanoemulsions of perfluorocarbons, which are known to be taken up by the macrophage/monocyte system, are widely used as contrast agents for preclinical applications. Herein, the most common protocols are described to obtain high-resolution and artifact-free19F MR images even for compounds with complex19F MR spectra. In addition, we report on the utilization of perfluorocarbons with individual spectral identities and targeting approaches to specifically visualize thrombi by19F MRI.

Key words

Fluorine MRI Perfluorocarbons Sterol-based post-insertion Active targeting Chemical shift imaging 

Notes

Acknowledgements

The authors would like to thank Prof. Jürgen Schrader (Düsseldorf) for his continuous support and encouragement as well as Prof. Rolf Schubert and Dr. Christoph Grapentin (Freiburg) for their enormous help in the development of the perfluorocarbon emulsions (PFCs). Furthermore, we would like to thank Prof. Cornelia Blume (Hannover) for providing us with the glomerulonephritis model. The work shown herein was supported financially by the Deutsche Forschungsgemeinschaft (DFG), the subproject Z2 of the SFB 612, subprojects B2 and B5 of the SFB 1116, and grants SCHR 154/13-1+2.

References

  1. 1.
    Bartusik D, Aebisher D (2014)19F applications in drug development and imaging—a review. Biomed Pharmacother 68(6):813–817. https://doi.org/10.1016/j.biopha.2014.07.012 CrossRefPubMedGoogle Scholar
  2. 2.
    Flögel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C, Schubert R, Schrader J (2008) In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation 118(2):140–148. https://doi.org/10.1161/CIRCULATIONAHA.107.737890 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bulte JW (2005) Hot spot MRI emerges from the background. Nat Biotechnol 23(8):945–946. https://doi.org/10.1038/nbt0805-945 CrossRefPubMedGoogle Scholar
  4. 4.
    Zhong J, Mills PH, Hitchens TK, Ahrens (2013) Accelerated fluorine-19 MRI cell tracking using compressed sensing. Magn Reson Med 69(6):1683–1690. https://doi.org/10.1002/mrm.24414
  5. 5.
    Krafft MP (2001) Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research. Adv Drug Deliv Rev 47(2–3):209–228CrossRefPubMedGoogle Scholar
  6. 6.
    Jacoby C, Temme S, Mayenfels F, Benoit N, Krafft MP, Schubert R, Schrader J, Flögel U (2014) Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half-lives and sensitivity. NMR Biomed 27(3):261–271. https://doi.org/10.1002/nbm.3059 CrossRefPubMedGoogle Scholar
  7. 7.
    Molnar D, Linders J, Mayer C, Schubert R (2016) Insertion stability of poly(ethylene glycol)-cholesteryl-based lipid anchors in liposome membranes. Eur J Pharm Biopharm 103:51–61. https://doi.org/10.1016/j.ejpb.2016.03.023 CrossRefPubMedGoogle Scholar
  8. 8.
    Temme S, Grapentin C, Quast C, Jacoby C, Grandoch M, Ding Z, Owenier C, Mayenfels F, Fischer JW, Schubert R, Schrader J, Flögel U (2015) Noninvasive imaging of early venous thrombosis by 19F magnetic resonance imaging with targeted perfluorocarbon nanoemulsions. Circulation 131(16):1405–1414. https://doi.org/10.1161/CIRCULATIONAHA.114.010962 CrossRefPubMedGoogle Scholar
  9. 9.
    Rosenkranz AR, Mendrick DL, Cotran RS, Mayadas TN (1999) P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation. J Clin Invest 103(5):649–659. https://doi.org/10.1172/JCI5183 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Temme S, Jacoby C, Ding Z, Bönner F, Borg N, Schrader J, Flögel U (2014) Technical advance: monitoring the trafficking of neutrophil granulocytes and monocytes during the course of tissue inflammation by noninvasive 19F MRI. J Leukoc Biol 95(4):689–697. https://doi.org/10.1189/jlb.0113032 CrossRefPubMedGoogle Scholar
  11. 11.
    Flögel U, Su S, Kreideweiss I, Ding Z, Galbarz L, Fu J, Jacoby C, Witzke O, Schrader J (2011) Noninvasive detection of graft rejection by in vivo (19) F MRI in the early stage. Am J Transplant 11(2):235–244. https://doi.org/10.1111/j.1600-6143.2010.03372.x CrossRefPubMedGoogle Scholar
  12. 12.
    Temme S, Bönner F, Schrader J, Flögel U (2012) 19F magnetic resonance imaging of endogenous macrophages in inflammation. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4(3):329–343. https://doi.org/10.1002/wnan.1163 CrossRefPubMedGoogle Scholar
  13. 13.
    Grenz A, Zhang H, Eckle T, Mittelbronn M, Wehrmann M, Kohle C, Kloor D, Thompson LF, Osswald H, Eltzschig HK (2007) Protective role of ecto-5′-nucleotidase (CD73) in renal ischemia. J Am Soc Nephrol 18(3):833–845. https://doi.org/10.1681/ASN.2006101141 CrossRefPubMedGoogle Scholar
  14. 14.
    Ahrens, Zhong J (2013) In vivo MRI cell tracking using perfluorocarbon probes and fluorine-19 detection. NMR Biomed 26(7):860–871. https://doi.org/10.1002/nbm.2948
  15. 15.
    Ahrens, Flores R, Xu H, Morel PA (2005) In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 23(8):983–987. https://doi.org/10.1038/nbt1121
  16. 16.
    Robinson BR, Houng AK, Reed GL (2000) Catalytic life of activated factor XIII in thrombi. Implications for fibrinolytic resistance and thrombus aging. Circulation 102(10):1151–1157CrossRefPubMedGoogle Scholar
  17. 17.
    Tung CH, Ho NH, Zeng Q, Tang Y, Jaffer FA, Reed GL, Weissleder R (2003) Novel factor XIII probes for blood coagulation imaging. Chembiochem 4(9):897–899. https://doi.org/10.1002/cbic.200300602 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Tuba Güden-Silber
    • 1
  • Sebastian Temme
    • 1
  • Christoph Jacoby
    • 1
  • Ulrich Flögel
    • 1
  1. 1.Experimental Cardiovascular Imaging, Department of Molecular CardiologyHeinrich Heine UniversityDüsseldorfGermany

Personalised recommendations