MRI Relaxation rates in Human cancer cells expressing MagA

The development of non-invasive imaging techniques to track labeled cells that have been transplanted into a human or animal may provide methods for guiding cellular therapies in humans as well as following the development of cancer in animal models. It has been demonstrated that cells labeled with iron particles can be detected by MRI. The earliest and most common means of iron labeling involves the uptake of exogenous superparamagnetic iron oxide (SPIO) particles. However, SPIO labeling may have limited potential for long-term cell tracking for a number of reasons, including iron redistribution after cell division and the potential for iron accumulation in tissue even after cell death. More recently, iron-labeling of cells has been accomplished using genetic engineering methods to overexpress proteins involved in iron transport and storage, with the aim of increasing intracellular levels of iron nanoparticles. For example, the magnetosome genes are capable of directing the synthesis of iron biominerals that impart magnetic sensitivity without cytotoxicity.

Our work involves MagA, a putative iron transport protein involved in magnetosome formation in magnetotactic bacteria. MagA has been overexpressed in mammalian cells, leading to observable changes in MRI signals. Measurements of MRI relaxation rates of MagA-expressing cells are important for optimizing cell detection and specificity, and for developing quantification methods.

Iron particles create a microscopically non-uniform magnetic field within the cells which in turn influences the fundamental MRI parameters, known as the relaxation times. Relaxation refers to the return of the nuclear magnetization to the equilibrium. This is the quantity detected in MRI. Magnetization has three components: x,y and z. The return of Mxy and Mz to the equlibrium , known as transverse and longitudinal magnetization respectively are characterized by a time constant Tand T1 respectively. Relaxation rates are the inverses of the realxation times.

Previously R2 (1/T2) relaxation rates were measured in MagA-expressing cells (2). We present measurements of the total transverse relaxation rate (R2*), its irreversible and reversible components (R2 and R2′, respectively) and the longitudinal relaxation rate (R1) from human tumor cells.

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MR Imaging of cells and measurement of the relaxation rates
Researchers
D. Goldhawk
Molecular Imaging
N. Gelman
Imaging (MRI) Scientist
F.S. Prato
Imaging Scientist and Imaging Director
R.T. Thompson
MRI



Technologies
3T PET/MR
Molecular Imaging

Collaborators
J. Koropatnick
Molecular Oncology
Future Directions
  • Investigate the reproducibility of relaxation rates for compact pellets.
  • Study relationship between relaxation rates and number of MagA cells per unit volume.
  • Compare relaxation rates for different expression systems, e.g. MagA vs Ferritin
Key Accomplishments

Our group has:

  • Developed reporter gene expression for MRI based cancer cell tracking.
  • Showed MagA, a putative iron transport protein, could be expressed in human breast cancer/melanoma(MDA-MB-435) cells, producing MR-detectable contrast in response to iron supplementation.
  • Devised a method of loading cells (both in pellet and suspension form) in manufactured wells and placing them in a gelatin phantom which in turn is then scanned to measure the MR relaxation rates.
  • Measured values of the MRI relaxation rates (including standard errors from curve fitting)where all relaxation rates are higher for iron-supplemented, MagA-expressing cells compared to parental controls.
  • Reported through reproducible experiments that MagA expression leads to increased relaxation rates in MDA-MB-435 cells, with the strongest relative effect occurring for R2′.
  • Patented our molecular imaging technologies e.g.

MagA reporter gene expression for MRI

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