Abstract

The process of metastasis formation involves the migration and 3-D invasion of tumor cells from a primary tumor to distant sites. We propose that the dynamics of the migration and invasion process of magnetically labeled tumor cells can be monitored in animal models over prolonged time periods using magnetic resonance imaging (MRI). Human breast carcinoma cells (MB-MDA-231) were labeled with superparamagnetic Fe2O3 iron oxide nanoparticles coated with poly-L-lysine. The particles are readily taken up by cancer cells and stored in intracellular clusters. During cell division, the nanoparticle clusters are divided and split unevenly between daughter cells (mean partitioning fraction 0.85 to 0.15). Nanoparticles are non-toxic, are not degraded by the cell and remain stable for at least 3 weeks. In vitro collagen gel assays show no differences in contractile properties and invasion behavior of magnetically labeled vs. non-labeled tumor cells. MRI of cells suspended in agarose gave a detection limit of the spin-spin-relaxation-rate above the agar background of approximately 70 cells per 1 mm3. The minimal detection volume of tumor cells in agarose was 25 μl. Detection limit and minimal volume were verified by injecting labeled cancer cells in mice. Spin-spin-relaxation-weighted (T2-weighted) and susceptibility-weighted images show a rapid relaxation behavior and pronounced phase shifts in the vicinity of the injection area compared to control scans. These studies demonstrate the feasibility of the method for long-term observation of cancer cell migration in vivo with MRI.

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