Development And Evaluation Of Magnetic Resonance Contras

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Abstract

By combining commonly used transfection agents (TA) that have high net positive electrostatic charge with Superparamagnetic dextran coated iron oxide nanoparticle (SPIO) such as the FDA approved agent Ferumoxides (FE), a complex is formed that can be used to magnetically label stem cells and other mammalian cells. Various concentrations of ferumoxides and poly-l-lysine (PLL) or protamine sulfate (Pro) complexes are used to magnetically label cells. Protamine Sulfate (Pro) is an FDA approved drug that is used to treat heparin anticoagulation was found to be a more efficient transfection agent and when complexed to FE in labeling cells. No adverse effect on the short or long-term toxicity, cell viability and functional capacity or differentiation capacity was observed following magnetic cell labeling with FE-PLL or FE-Pro. Systemically administered Fe-PLL labeled hematopoietic Sca1+ bone marrow cells can be detected by in vivo magnetic resonance imaging (MRI) in a mouse brain tumor model. MRI was performed during tumor growth. Mice that received labeled cells demonstrated hypointense regions within the tumor that evolved over time and developed a continuous dark hypointense ring at a consistent time point. Histology showed iron-labeled cells around the tumor rim in labeled mice, which expressed CD31 and von Willebrand factor, indicating the transplanted cells detected in the tumor have differentiated into endothelial-like cells. These results demonstrate that MRI can detect the incorporation of magnetically labeled bone marrow-derived precursor cells into tumor vasculature as part of ongoing angiogenesis and neovascularization.