Gene-based contrast for MRI

We are developing reporter gene expression for MRI.  This imaging modality relies on tissue and cellular contrast agents that perturb the local magnetic field, providing a signal that can be spatially and temporally related to the subject.  While superparamagnetic iron oxide (SPIO) nanoparticles are effective contrast agents, tracking cells using these synthetic particles is limited by their dilution during cell division, degradation by the cell, and lack of inherent biological activity.  To address these shortcomings, we are drawing on the genetic activity of magnetotactic bacteria, which form membrane-enclosed iron biominerals, termed magnetosomes. These are similar to SPIO in size, composition and magnetic properties.  To induce the formation of magnetosome-like particles in mammalian cells, we are overexpressing the MagA gene, a putative iron transporter from M. magneticum sp. AMB-1.  Thus, through genetic engineering we are imparting magnetic characteristics to cells and creating a tracking system suitable for long-term, repetitive imaging of cellular function, including migration, mitosis, differentiation and cell death. 

 

test

Imaging Tumours Formed from MDA-MB-435 Cells. Nude mice received subcutaneous injections of transfected or untransfected cells into the left or right hind limb, respectively. The axial cross section was captured 6 weeks post-injection using custom made RF and gradient coil inserts on a 3T scanner. MagA expression increases the signal void in tumour tissue.
Researchers
D. Goldhawk
Molecular Imaging
S. Dhanvantari
Molecular Imaging
R.T. Thompson
MRI
R.Z. Stodilka
Hybrid Imaging
T.-Y. Lee
PET/CT
M.S. Kovacs
PET Radiochemistry
F.S. Prato
Bioelectromagnetics
G. Wisenberg
Cardiac Imaging
B. Chronik
PET/MRI

Technologies
3T PET/MR
Bioelectromagnetics
Cyclotron & PET Radiochemistry
Molecular Imaging
PET/CT
SPECT/CT

Collaborators
J. Koropatnick
Molecular Oncology
P. Foster
MRI
C. Lemaire
MRI
Future Directions

Funding of molecular imaging research at the Lawson is a partnership between governmental, institutional and private business sectors.  In the clinical setting, there is an immediate need for tracking cell therapy, such as stem cells implanted to regenerate function in a failing organ.  In preclinical research, cell tracking can be used to monitor the growth of metastasic cells and to evaluate the efficacy of anti-cancer therapies.  We anticipate future commercialization opportunities for magnetosome gene expression vectors that permit reporter gene expression for MRI.

Key Accomplishments

Molecular imaging with MRI using MagA gene expression in eukaryotic cells has been patented and advanced from provisional filing to national phase in both Canada and the USA.  In addition, global interest in MagA expression has resulted in negotiation of 3 Material and Information Transfer and Use Agreements. Through Lawson collaborations, examination of MagA expression in cancer cell cultures has been expanded to MRI of MagA-expressing tumours in a preclinical rodent model of cancer growth and metastasis (see figure; Mol. Imaging (2009) 8, 129). This research will complement developments in other imaging modalities and reporter gene expression systems.  In particular, hybrid imaging with PET/MRI will permit simultaneous cell tracking with two different reporter genes and two different imaging methods, combining the best in sensitivity (nuclear) and resolution (MR). This work is directly applicable to development of MagA expression for a cardiac model of progenitor cell transplantation, and will complement studies using cells radiolabelled with 111Indium for SPECT. 

 

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