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In vivo imaging platform for tracking immunotherapeutic cells

Nature Biotechnology volume 23, pages 983–987 (2005)Cite this article

Abstract

Cellular therapeutics show great promise for the treatment of disease, but few noninvasive techniques exist for monitoring the cells after administration. Here we present a magnetic resonance imaging (MRI) technology that uses perfluoropolyether (PFPE) agents to track cells in vivo. Fluorine MRI selectively images only the labeled cells, and a 'conventional' 1H image places the cells in their anatomical context. We labeled phenotypically defined dendritic cells (DCs) with PFPE ex vivo and observed efficient intracellular uptake of the PFPE with little effect on DC function. We injected labeled DCs into tissue or intravenously in mice and then tracked the cells in vivo using 19F MRI. Although we focused on DCs, which are being developed as immunotherapeutics for cancer and autoimmune diseases, this technology should be useful for monitoring a wide range of cell types in vivo.

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Figure 1: Microscopy of PFPE-labeled DCs.
Figure 2: Cytotoxicity, proliferation, and phenotype studies in PFPE-labeled FSDCs in vitro.
Figure 3: In vivo MRI of PFPE-labeled DCs in mouse.
Figure 4: FACS analysis of DCs in excised lymph nodes following foot pad injection.

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Acknowledgements

We thank Chris Navara and Joseph Suhan for their microscopy expertise and Joyce Horner for assistance with animal handling. We also acknowledge helpful discussion with Mangala Srinivas, Lauren Ernest, Kevin Hitchens, Seong-Gi Kim, Clinton Robison, Ulrike DeMarco and Adam Linstedt. This work was funded by the National Institutes of Health RO1-EB003453, P41-EB001977, P50-ES012359, and the Ethel Vincent Charitable Trust.

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Authors and Affiliations

  1. Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, 15213, Pennsylvania, USA

    Eric T Ahrens & Hongyan Xu

  2. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, 152611, Pennsylvania, USA

    Rafael Flores & Penelope A Morel

Authors
  1. Eric T Ahrens
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  2. Rafael Flores
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  3. Hongyan Xu
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  4. Penelope A Morel
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Correspondence to Eric T Ahrens.

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Supplementary information

Supplementary Fig. 1

19F NMR spectrum of intracellular PFPE emulsion particles in FSDCs. (PDF 60 kb)

Supplementary Fig. 2

Intracellular retention of PFPE over time in cultured FSDCs. (PDF 73 kb)

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Ahrens, E., Flores, R., Xu, H. et al. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 23, 983–987 (2005). https://doi.org/10.1038/nbt1121

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