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Tracking cancer cells by MRI using magnetosome gene expression

¹ Imaging, Lawson Health Research Institute, London, Ontario, Canada; ² Physics, University of Waterloo, Waterloo, Ontario, Canada; ³ Diabetes & Metabolism, Lawson Health Research Institute, London, Ontario, Canada

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Objectives: Development of reporter gene expression for MRI is progressing in part through discovery of genes from magnetotactic bacteria, which acquire their magnetic properties from magnetosomes: membrane-enclosed iron biominerals. We have used the magnetosome gene MagA, an iron transporter, to provide intracellular contrast in mammalian cells and enable molecular imaging by MRI. Characterization of transfected cancer cells shows that iron uptake and retention is facilitated by MagA expression.

Methods: MRI was performed on neuroblastoma (N2A) and breast cancer (MDA MB 435) cells, stably expressing MagA or its E137V mutation. Cells were cultured in the presence or absence of ferric nitrate. Imaging at 11T was performed on live cells mounted in gelatin. Iron retention in cell lysates was quantified by inductively coupled plasma mass spectrometry. Protein was measured using the BCA assay.

Results: High field MRI shows that MagA overexpression increases cellular contrast in mammalian cancer cells. In contrast, the signal from overexpression of mutant MagA is comparable to background. Analysis of cellular iron indicates that MagA expression increases the sensitivity of mammalian cells to extracellular iron concentration.

Conclusions: MagA expression increases cellular contrast in mammalian cells, suitable to reporter gene activity for MRI. We propose a two-fold mechanism of action whereby MagA decreases the threshold for iron uptake into cells and facilitates formation of intracellular magnetite. MagA expression will be used to non-invasively track cancer cell growth and metastasis in preclinical animal models.

Research Support: This project was funded through the Cancer Imaging Network of Ontario supported by Cancer Care Ontario.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Goldhawk, D. Articles by Prato, F. PubMed Articles by Goldhawk, D. Articles by Prato, F.