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¹⁹F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons

Kathryn C. Partlow^*, Junjie Chen^*, Jason A. Brant^*, Anne M. Neubauer^*, Todd E. Meyerrose^*, Michael H. Creer, Jan A. Nolta^*, Shelton D. Caruthers^*,, Gregory M. Lanza^* and Samuel A. Wickline^*,1

^* Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA;

Departments of Pathology and Laboratory Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA; and

Philips Medical Systems, Andover, Massachusetts, USA

¹Correspondence: Washington University School of Medicine, Campus Box 8215, 660 South Euclid Ave., St. Louis, MO, USA 63110. E-mail: saw{at}howdy.wustl.edu

MRI has been employed to elucidate the migratory behavior of stem/progenitor cells noninvasively in vivo with traditional proton (¹H) imaging of iron oxide nanoparticle-labeled cells. Alternatively, we demonstrate that fluorine (¹⁹F) MRI of cells labeled with different types of liquid perfluorocarbon (PFC) nanoparticles produces unique and sensitive cell markers distinct from any tissue background signal. To define the utility for cell tracking, mononuclear cells harvested from human umbilical cord blood were grown under proendothelial conditions and labeled with nanoparticles composed of two distinct PFC cores (perfluorooctylbromide and perfluoro-15-crown-5 ether). The sensitivity for detecting and imaging labeled cells was defined on 11.7T (research) and 1.5T (clinical) scanners. Stem/progenitor cells (CD34⁺CD133⁺CD31⁺) readily internalized PFC nanoparticles without aid of adjunctive labeling techniques, and cells remained functional in vivo. PFC-labeled cells exhibited distinct ¹⁹F signals and were readily detected after both local and intravenous injection. PFC nanoparticles provide an unequivocal and unique signature for stem/progenitor cells, enable spatial cell localization with ¹⁹F MRI, and permit quantification and detection of multiple fluorine signatures via ¹⁹F MR spectroscopy. This method should facilitate longitudinal investigation of cellular events in vivo for multiple cell types simultaneously.—Partlow, K. C., Chen, J., Brant, J. A., Neubauer, A. M., Meyerrose, T. E., Creer, M. H., Nolta, J. A., Caruthers, S. D., Lanza, G. M., Wickline, S. A. ¹⁹F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons.

Key Words: endothelial progenitor cells • nanoparticles • contrast agent

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