MRI detection of macrophages labeled using micrometer-sized iron oxide particles

Purpose: To evaluate cellular labeling of immune cells using micron-sized iron oxide particles (MPIOs) and evaluate the MR relaxivity and MRI detection of the labeled cells. Materials and Methods: Immune cells isolated from mice and rats were labeled with three different sizes of MPIO particles (0.35, 0.90, or 1.63 mu m). These labeled cells were characterized using transmission electron microscopy (TEM), fluorescence microscopy, flow cytometry, MR relaxometry, and MRI. Results: Macrophage uptake of MPIOs was found to be highest for the 1.63-mu m size particles. MR relaxivity measurements indicated greater spin-spin relaxation for MPIO-labeled cells relative to cells labeled with nanometer-sized ultra-small superparamagnetic iron oxide (USPIO) particles with similar iron content. TEM and fluorescence microscopy indicated cellular uptake of multiple MPIO particles per cell. Macrophages labeled with 1.63-mu m MPIOs had an average cellular iron uptake of 39.1 pg/cell, corresponding to approximately 35 particles per cell. Conclusion: Cells labeled with one or more MPIO particles could be readily detected ex vivo at 11.7 Tesla and after infusion of the MPIO-labeled macrophages into the kidney of a rat, hypointense regions of the outer cortex are observed, in vivo, by MRI at 4.7 Tesla.