Relaxometry of Bacterially Derived Organelles: A Novel Class of MRI Contrast Agent for Cell Labeling and Tracking

Purpose: Superparamagnetic iron oxide (SPIO) contrast agents have been used for a number of years to label cells for tracking by MRI. However, these particles are significantly disadvantaged in longitudinal imaging because, as cells divide, the amount of iron per cell decreases and eventually the labeled cells can no longer be detected. MR reporter genes exist that allow cells to produce iron particles, but these have met with limited success. These reporters also require modification to the host cell genome, making them less translatable. Recently, Bell Biosystems Inc. (Palo Alto, CA) has developed a bacterial-derived magnetic pseudo-organelle known as the “Magnelle” from magnetotactic bacteria, building on previous work that explored bacteria as a potential MR contrast agent. Since magnetotactic bacteria naturally generate magnetosomes (chains of lipid bilayer enclosed compartments containing magnetite crystals) through the coordination of over 100 genes, they may have certain advantages as MR contrast agents. Some MR reporter gene candidates are based on magnetotactic bacterial genes such as magA and mms6. Since Magnelles were derived from bacteria, they have the ability to self-replicate, making them interesting candidates for labeling and longitudinal evaluation of cells. This is crucial for many emerging applications, particularly evaluation of stem cell and other cell-based therapies. This work presents initial characterization of the MRI relaxivity properties (both r1 and r2) of Magnelles, their cell loading, as well as ex vivo imaging characteristics using a model breast cancer cell line.