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

• Published in: Molecular imaging and biology Vol. 13; no. 5; pp. 825 - 839
• Main Authors: Chen, Chih-Lung, Zhang, Haosen, Ye, Qing, Hsieh, Wen-Yuan, Hitchens, T. Kevin, Shen, Hsin-Hsin, Liu, Li, Wu, Yi-Jen, Foley, Lesley M., Wang, Shian-Jy, Ho, Chien
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.10.2011; Springer Nature B.V
• Subjects: Animals; Cells, Cultured; Ferric Compounds - chemistry; Flow Cytometry; Imaging; Magnetic Resonance Imaging - methods; Medicine; Medicine & Public Health; Metal Nanoparticles; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Particle Size; Radiology; Rats; Research Article; Iron oxide particles; Rat heart transplant model; Cellular MRI; labeling; Cells; ITRI-IOP
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-010-0430-x

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.