Water-soluble lipophilic MR contrast agents for cell membrane labeling

Abstract

Long-term cell tracking using MR imaging necessitates the development of contrast agents that both label and are retained by cells. One promising strategy for long-term cell labeling is the development of lipophilic Gd(III)-based contrast agents that anchor into the cell membrane. We have previously reported the efficacy of monomeric and multimeric lipophilic agents and showed that the monomeric agents have improved labeling and contrast enhancement of cell populations. Here, we report on the synthesis, characterization, and in vitro testing of a series of monomeric lipophilic contrast agents with varied alkyl chain compositions. We show that these agents disperse in water, localize to the cell membrane, and label HeLa and MCF7 cells effectively. Additionally, these agents have up to tenfold improved retention in cells compared to clinically available ProHance®.

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Acknowledgments

This work was supported by the National Institutes of Health (NIH Grants R01EB005866 and P01HL108795) and by a National Science Foundation Graduate Research Fellowship (C. C.). Imaging was performed at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. MRI was performed on the 7 T Bruker Pharmscan system purchased with the support of NCRR 1S10RR025624-01. Metal analysis was performed at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center NNA06CB93G.

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Correspondence to Thomas J. Meade.

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Carney, C.E., MacRenaris, K.W. & Meade, T.J. Water-soluble lipophilic MR contrast agents for cell membrane labeling. J Biol Inorg Chem 20, 971–977 (2015). https://doi.org/10.1007/s00775-015-1280-4

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Keywords

  • MRI
  • Contrast agents
  • Gadolinium
  • Cell membrane
  • Cell labeling