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Published on: March 20, 2013
Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological
Christoph Jacoby1, Sebastian Temme, Friederike Mayenfels
1Institut für Molekulare Kardiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Abstract:
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.
Insights
Perfluoro-15-crown-5 ether (PFCE) shows promise for (19)F MRI inflammation imaging but has a long biological half-life. Alternative perfluorocarbons (PFCs) like PFOB and F-44E demonstrate shorter half-lives and viable in vivo inflammation detection.
Area of Science:
- Medical Imaging
- Biomedical Engineering
- Fluorine Chemistry
Background:
- (19)F MRI enables inflammation assessment via perfluorocarbon (PFC) uptake by macrophages.
- Perfluoro-15-crown-5 ether (PFCE) is ideal for fluorine detection but has an excessively long biological half-life, limiting clinical use.
- Investigating alternative PFCs with shorter biological half-lives and high fluorine content is crucial for advancing (19)F MR inflammation imaging.
Purpose of the Study:
- To evaluate novel, non-toxic perfluorocarbons (PFCs) for in vivo (19)F MR inflammation imaging.
- To determine the biological half-lives and in vivo inflammation imaging sensitivity of perfluorooctyl bromide (PFOB), perfluorodecalin (PFD), and trans-bis-perfluorobutyl ethylene (F-44E).
- To identify a suitable PFC for potential future clinical translation of (19)F MR inflammation imaging.
Main Methods:
- Utilized sine-squared acquisition-weighted 3D chemical shift imaging with custom reconstruction software for artifact-free imaging of PFCs.
- Employed a Nutall window to maximize signal-to-noise ratio with minimal localization error.
- Assessed PFC retention times in murine liver and spleen at 9.4 T and evaluated in vivo inflammation imaging sensitivity using an ear clip injury model.
Main Results:
- Estimated biological half-lives were 9 days (PFD), 12 days (PFOB), and 28 days (F-44E), significantly shorter than PFCE (>250 days).
- PFOB and F-44E showed 37% and 43% of PFCE signal intensity in the inflammation model, respectively.
- PFD did not yield detectable signals in the in vivo inflammation model.
Conclusions:
- Perfluorooctyl bromide (PFOB) and trans-bis-perfluorobutyl ethylene (F-44E) are promising alternatives to PFCE for (19)F MR inflammation imaging due to shorter biological half-lives.
- PFOB demonstrates the most favorable characteristics for potential translation to human clinical applications in monitoring inflammatory processes.
- Further research into PFOB and F-44E could advance the clinical utility of (19)F MR imaging for inflammatory diseases.
