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Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis

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Abstract

Purpose

The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo.

Procedures

Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide. The subsequent conjugation of monoclonal anti-CD3 antibody with IOPC made it possible to construct a magnetic resonance imaging (MRI) contrast agente (CA) that targets T cells, named IOPC-CD3.

Results

IOPC-CD3 was found to have high transverse relaxivity, good targeting selectivity, and good safety profile in vitro. The utility of this newly synthesized CA was explored in an in vivo rodent collagen-induced arthritis (CIA) model of rheumatoid arthritis. Serial MRI experiments revealed a selective decrease in the signal-to-noise ratio of the femoral growth plates of CIA rats infused with IOPC-CD3, with this finding being consistent with immunohistochemical results showing the accumulation of T cells and iron oxide nanoparticles in the corresponding region.

Conclusions

Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.

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Acknowledgments

This study was supported by a grant from the National Science Council (NSC 99-2314-B-016-31-MY3).

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Authors and Affiliations

  1. Biomedical Engineering Devices Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan

    Chih-Lung Chen, Chen-Hsuan Lin, Yung-Chu Chen, Wen-Yuan Hsieh & Shian-Jy Wang

  2. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Institute for Radiological Research, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Tiing Yee Siow

  3. Body Organ Biomedical Corporation, Taipei, Taiwan

    Cheng-Hung Chou

  4. Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Road, Nangkang, Taipei, 11529, Taiwan

    Ming-Huang Lin & Chen Chang

Authors
  1. Chih-Lung Chen
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  2. Tiing Yee Siow
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  4. Chen-Hsuan Lin
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  9. Chen Chang
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Correspondence to Chen Chang.

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Conflict of Interest

The authors report having a pending patent related to subject matter discussed in this article.

Additional information

Chih-Lung Chen and Tiing Yee Siow these authors made equal contributions.

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Chen, CL., Siow, T.Y., Chou, CH. et al. Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis. Mol Imaging Biol 19, 233–244 (2017). https://doi.org/10.1007/s11307-016-1001-6

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  • DOI: https://doi.org/10.1007/s11307-016-1001-6

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