Imaging tumor growth non-invasively using expression of MagA or modified ferritin subunits to augment intracellular contrast for repetitive MRI

Mol Imaging Biol. 2014 Feb;16(1):63-73. doi: 10.1007/s11307-013-0661-8.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Contrast Media*
  • Ferritins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Genes, Bacterial / genetics*
  • Humans
  • Intracellular Space / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Nude
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Protein Subunits / metabolism*
  • Signal-To-Noise Ratio
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Protein Subunits
  • Ferritins