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Paramagnetic Fluorinated Nanoemulsions for in vivo F-19 MRI

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A Correction to this article was published on 30 September 2021

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Abstract

Purpose

We aim to develop perfluorocarbon-based nanoemulsions with improved sensitivity for detection of inflammatory macrophages in situ using F-19 MRI. Towards this goal, we evaluate the feasibility of nanoemulsion formulation incorporating a metal chelate in the fluorous phase which shortens the F-19 longitudinal relaxation rate and image acquisition time.

Procedures

Perfluorinated linear polymers were conjugated to metal-binding tris-diketonate, blended with unconjugated polymers, and emulsified in water. Phospholipid-based surfactant was used to stabilize nanoemulsion and provide biocompatibility. Nanoemulsions were metalated with the addition of ferric salt to the buffer. Physical stability of surfactant and nanoemulsion was evaluated by mass spectrometry and dynamic light scattering measurements. Nanoemulsions were injected intravenously into a murine granuloma inflammation model, and in vivo19F/1H MRI at 11.7 T was performed.

Results

We demonstrated stability and biocompatibility of lipid-based paramagnetic nanoemulsions. We investigated potential oxidation of lipid in the presence of metal chelate. As a proof of concept, we performed non-invasive monitoring of macrophage burden in a murine inflammation model following intravenous injection of nanoemulsion using in vivo F-19 MRI.

Conclusion

Lipid-based nanoemulsion probes of perfluorocarbon synthesized with iron-binding fluorinated β-diketones can be formulated for intravenous delivery and inflammation detection in vivo.

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Funding

Funding for ETA was provided by National Institutes of Health (NIH) grants R01-EB017271, R01-EB024015, R01-CA134633, and the California Institute for Regenerative Medicine LA1-C12-06919. JR received funding from NIH T32-EB005970.

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Authors and Affiliations

  1. Department of Radiology, University of California, San Diego, 9500 Gilman Dr. #0695, La Jolla, CA, 92093-0695, USA

    Junsung Rho, Emma Stares, Deanne Lister, Benjamin Leach & Eric T. Ahrens

  2. Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA

    Stephen R. Adams

Authors
  1. Junsung Rho
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  2. Emma Stares
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  3. Stephen R. Adams
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  4. Deanne Lister
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  5. Benjamin Leach
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  6. Eric T. Ahrens
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Corresponding author

Correspondence to Eric T. Ahrens.

Ethics declarations

Animal experiments were performed in accordance with the guidelines provided by the UCSD Institutional Animal Care and Use Committee (IACUC) and the National Institute of Health Guide for the Care and Use of Laboratory Animals.

Conflict of Interest

ETA is a founder, consultant, member of the advisory board and shareholder of Celsense, Inc. The other authors declare that they have no conflict of interest.

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Rho, J., Stares, E., Adams, S.R. et al. Paramagnetic Fluorinated Nanoemulsions for in vivo F-19 MRI. Mol Imaging Biol 22, 665–674 (2020). https://doi.org/10.1007/s11307-019-01415-5

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  • DOI: https://doi.org/10.1007/s11307-019-01415-5

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