A New Nano-sized Iron Oxide Particle with High Sensitivity for Cellular Magnetic Resonance Imaging

Abstract

Purpose-In this study, we investigated the labeling efficiency and magnetic resonance imaging (MRI) signal sensitivity of a newly synthesized, nano-sized iron oxide particle (IOP) coated with polyethylene glycol (PEG), designed by Industrial Technology Research Institute (ITRI).Procedures-Macrophages, bone-marrow-derived dendritic cells, and mesenchymal stem cells (MSCs) were isolated from rats and labeled by incubating with ITRI-IOP, along with three other iron oxide particles in different sizes and coatings as reference. These labeled cells were characterized with transmission electron microscopy (TEM), light and fluorescence microscopy, phantom MRI, and finally in vivo MRI and ex vivo magnetic resonance microscopy (MRM) of transplanted hearts in rats infused with labeled macrophages.Results-The longitudinal (r 1 ) and transverse (r 2 ) relaxivities of ITRI-IOP are 22.71 and 319.2 s −1 mM −1 , respectively. TEM and microscopic images indicate the uptake of multiple ITRI-IOP particles per cell for all cell types. ITRI-IOP provides sensitivity comparable or higher than the other three particles shown in phantom MRI. In vivo MRI and ex vivo MRM detect punctate spots of hypointensity in rejecting hearts, most likely caused by the accumulation of macrophages labeled by ITRI-IOP.Conclusion-ITRI-IOP, the nano-sized iron oxide particle, shows high efficiency in cell labeling, including both phagocytic and non-phagocytic cells. Furthermore, it provides excellent sensitivity in T 2 *-weighted MRI, and thus can serve as a promising contrast agent for in vivo cellular MRI.

Cellular and Functional Imaging of Cardiac Transplant Rejection

“…6). Multimodality cell tracking probes allow for both MR and optical imaging [9•, 22•, 25•, 26•, 45–48]. In addition, MR probes with different colors of fluorescent tags can facilitate molecular and cellular mechanistic investigation for rejection biology.…”

“…We have been developing a new class of iron oxide particles [48] that can be more readily ingested by the non-phagocytotic cell types, for efficient labeling for cellular MRI. The newly synthesized, PEG-coated, nano-sized iron oxide particle, ITRI-IOP (Fig.…”

“…The slopes of the linear fitting are the longitudinal and transverse relaxivities, r 1 and r 2 , of the particles, respectively. (From Chen et al [48]; with permission)…”

“…Light microscope images (×400) of d macrophages, e dendritic cells, and f MSCs after Prussian blue staining also show the presence of iron in the cell cytoplasm (iron shown as blue ). (From Chen et al [48]; with permission)…”

Mesenchymal Stem Cells as Vehicles for Targeted Therapies

“…The nanoparticles of choice for such cell labeling studies in MSCs were superparamagnetic iron oxide (SPIO) particles which can be used to track the biodistribution and migration of transplanted cells by MRI and other imaging methods (Arbab et al, 2004;Bulte et al, 2005;Chen et al, 2010a;Jo et al, 2010;Kostura et al, 2004;Loebinger et al, 2009b;Reddy et al, 2010;Walczak et al, 2005). Tracking labeled MSCs after transplantation will enable a better understanding of the dynamics of cell-tissue interactions and help improve the design of stem cell therapies by optimizing cell manufacturing and cell delivery protocols Srinivas et al, 2010).…”