title: Imaging tumor growth non-invasively using expression of MagA or modified ferritin subunits to augment intracellular contrast for repetitive MRI.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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-cm(3) 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.
authors.affiliation: Imaging Program, Lawson Health Research Institute, London, ON, Canada.
authors.forename: Roja
authors.initials: R
authors.lastname: Rohani
authors.forename: Rene
authors.initials: R
authors.lastname: Figueredo
authors.forename: Yves
authors.initials: Y
authors.lastname: Bureau
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Paula
authors.initials: P
authors.lastname: Foster
authors.forename: R Terry
authors.initials: RT
authors.lastname: Thompson
authors.forename: Frank S
authors.initials: FS
authors.lastname: Prato
authors.forename: Donna E
authors.initials: DE
authors.lastname: Goldhawk
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003287:Contrast Media; D005293:Ferritins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005798:Genes, Bacterial / Q000235:genetics*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D021122:Protein Subunits / Q000378:metabolism*; D059629:Signal-To-Noise Ratio; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media; D021122:Protein Subunits; D005293:Ferritins