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

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Molecular Imaging and Biology Aims and scope Submit manuscript

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 T2*-weighted MRI, and thus can serve as a promising contrast agent for in vivo cellular MRI.

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Abbreviations

BN rat:

Brown Norway rat

DA rat:

Dark Agouti rat

DLS:

Dynamic light scattering

ECG:

Electrocardiography

FACS:

Fluorescent-activated cell sorting

FDA:

Food and Drug Administration

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

MRM:

Magnetic resonance microscopy

MPIO:

Micron-sized superparamagnetic iron oxide particles

MSCs:

Mesenchymal stem cells

PBS:

Phosphate-buffered saline

PEG:

Polyethylene glycol

POD:

Post-operation day

r 1 :

Longitudinal relaxivity

r 2 :

Transverse relaxivity

RES:

Reticuloendothelial system

SPIO:

Superparamagnetic iron oxide particles

T 1 :

Longitudinal relaxation time

T 2 :

Transverse relaxation time

TEM:

Transmission electron microscopy

TE:

Echo time

TR:

Repetition time

USPIO:

Ultrasmall superparamagnetic iron oxide particles

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Acknowledgements

We thank Mr. Joseph P. Suhan, Department of Biological Sciences, Carnegie Mellon University, for excellent technical assistance in the TEM measurements. We also thank Dr. Steve R. Roffler of the Institute of Biomedical Sciences, Academia Sinica, Taiwan for kindly providing us with his anti-PEG AGP3 antibody (SR-66). C.-L. Chen, W.-Y. Hsieh, H.-H. Shen, and S.-J. Wang are supported by the Industrial Technology Research Institute, Taiwan. We also acknowledge the research support from NIH grants (R01HL-081349 and P41EB-00197 to C. Ho).

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The authors declare that they have no conflict of interest.

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Correspondence to Chien Ho.

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Chih-Lung Chen and Haosen Zhang contributed equally.

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Chen, CL., Zhang, H., Ye, Q. et al. A New Nano-sized Iron Oxide Particle with High Sensitivity for Cellular Magnetic Resonance Imaging. Mol Imaging Biol 13, 825–839 (2011). https://doi.org/10.1007/s11307-010-0430-x

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  • DOI: https://doi.org/10.1007/s11307-010-0430-x

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