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Imaging Tumor Growth Non-invasively Using Expression of MagA or Modified Ferritin Subunits to Augment Intracellular Contrast for Repetitive MRI

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Abstract

Purpose

The bacterial gene MagA imparts magnetic properties to mammalian cells and provides a basis for cell tracking by magnetic resonance imaging (MRI). In a mouse model of tumor growth from transplanted cells, we used repetitive MRI to demonstrate the in vivo imaging potential of MagA expression relative to a modified ferritin overexpression system, lacking regulation through iron response elements (HF + LF).

Procedures

Subcutaneous tumor xenografts were monitored weekly from days 2 to 34 post-injection. Small animal MRI employed balanced steady-state free precession. Imaging was correlated with tumor histology using hematoxylin, Prussian Blue, Ki-67, and BS-1 lectin.

Results

Tumor heterogeneity with respect to tissue morphology and magnetic resonance (MR) contrast was apparent within a week of cell transplantation. In MagA- and HF + LF-expressing tumors, MR contrast enhancement was recorded up to day 20 post-injection and 0.073-cm3 tumor volumes. MagA-expressing tumors showed increases in both quantity and quality of MR contrast as measured by fractional void volume and contrast-to-noise ratio, respectively. MR contrast in both MagA- and HF + LF-expressing tumors was maximal by day 13, doubling fractional void volume 1 week ahead of controls.

Conclusions

MagA- and HF + LF-expressing tumor xenografts augment MR contrast after 1 week of growth. MagA expression increases MR contrast within days of cell transplantation and provides MR contrast comparable to HF + LF. MagA has utility for monitoring cell growth and differentiation, with potential for in vivo detection of reporter gene expression using MRI.

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Acknowledgments

The authors thank Aaron Chapman, Becky McGirr, and Alice Wang for technical assistance. Tom Crohns performed the cryosectioning. This research was partially funded by grants from the Cancer Imaging Network of Ontario, supported by Cancer Care Ontario, and the Lawson Internal Research Fund. DEG, RTT, and FSP are supported by the Ontario Research Fund Research Excellence project 02-038, Imaging for Cardiovascular Therapeutics: myocardial cell therapy for heart failure.

Conflicts of interest

Drs. Goldhawk, Prato, and Thompson are authors on a patent describing the use of magnetosome genes in eukaryotic cells.

Author information

Authors and Affiliations

  1. Imaging Program, Lawson Health Research Institute, London, ON, Canada

    Roja Rohani, Yves Bureau, R. Terry Thompson, Frank S. Prato & Donna E. Goldhawk

  2. Cancer Research Laboratory Program, London Regional Cancer Program, London, ON, Canada

    Rene Figueredo & James Koropatnick

  3. Department of Medical Biophysics, Western University, London, ON, Canada

    Yves Bureau, Paula Foster, R. Terry Thompson, Frank S. Prato & Donna E. Goldhawk

  4. Department of Oncology, Western University, London, ON, Canada

    James Koropatnick

  5. Imaging Program, Robarts Research Institute, London, ON, Canada

    Paula Foster

  6. Collaborative Graduate Program in Molecular Imaging, Western University, London, ON, Canada

    Paula Foster & Donna E. Goldhawk

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  1. Roja Rohani
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Correspondence to Donna E. Goldhawk.

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Rohani, R., Figueredo, R., Bureau, Y. et al. Imaging Tumor Growth Non-invasively Using Expression of MagA or Modified Ferritin Subunits to Augment Intracellular Contrast for Repetitive MRI. Mol Imaging Biol 16, 63–73 (2014). https://doi.org/10.1007/s11307-013-0661-8

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  • DOI: https://doi.org/10.1007/s11307-013-0661-8

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