Chih-Lung Chen1, Tiing Yee Siow2, Cheng-Hung Chou3, Chen-Hsuan Lin1, Ming-Huang Lin4, Yung-Chu Chen1, Wen-Yuan Hsieh1, Shian-Jy Wang1, Chen Chang5. 1. Biomedical Engineering Devices Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. 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. 3. Body Organ Biomedical Corporation, Taipei, Taiwan. 4. Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Road, Nangkang, Taipei, 11529, Taiwan. 5. Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Road, Nangkang, Taipei, 11529, Taiwan. bmcchen@ibms.sinica.edu.tw.
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.
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.
Entities:
Keywords:
CD3; Carboxylation; Collagen-induced arthritis; Iron oxide nanoparticles; MRI; Molecular imaging; Polyethylene glycol; Rat; Rheumatoid arthritis; T cell imaging
Authors: Erwin L A Blezer; Lisette H Deddens; Gijs Kooij; Joost Drexhage; Susanne M A van der Pol; Arie Reijerkerk; Rick M Dijkhuizen; Helga E de Vries Journal: Contrast Media Mol Imaging Date: 2014-04-22 Impact factor: 3.161
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