Labeling of cancer cell with magnetic nanoparticles for magnetic resonance imaging

The process of migration and metastasis formation of tumor cells in the living organism is poorly understood. An experimental approach to study metastasis formation is to inject labeled cancer cells into research animals and to follow the cell migration and invasion pathway over prolonged periods of time. This report investigates the use and applicability of iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent for long-term cell labeling. Flame-spray pyrolysis γFe₂O₃ nanoparticles were stabilized and biofunctionalized by coating them with poly-l-lysine (PLL). Approximately 10,000 cells were incubated with 1 ìg of particles for 24 h. PLL-coated particles are readily taken up by cancer cells and are stored in intracellular clusters. During cell division, the nanoparticle clusters are divided and split between daughter cells. TEM imaging revealed no membrane formation around the nanoparticle clusters. Nanoparticles are not degraded by the cell and remain stable for at least 3 weeks. MRI imaging of cells suspended in 2% agar was used to estimate the detection limit. The detection limit of the R2* relaxation rate above the agar background is 25 cells/mm³, and the R2 detection limit is 70 cells/mm³. The iron specificity, however, is higher in the R2 relaxation rate image. These results suggest that PLL-coated flame spray pyrolysis γFe ₂O₃ nanoparticles can be used as a MRI contrast agent for longterm studies of cancer cell migration in vivo. © 2009 Springer-Verlag.