Theranostics 2016; 6(1):118-130. doi:10.7150/thno.13069

Research Paper

Bispecific Antibody Conjugated Manganese-Based Magnetic Engineered Iron Oxide for Imaging of HER2/neu- and EGFR-Expressing Tumors

Shou-Cheng Wu1,#, Yu-Jen Chen1,#, Hsiang-Ching Wang2, Min-Yuan Chou2, Teng-Yuan Chang3, Shyng-Shiou Yuan4, Chiao-Yun Chen5, Ming-Feng Hou6, John Tsu-An Hsu1,3,✉, Yun-Ming Wang1,7,✉

1. Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan
2. Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 310, Taiwan
3. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan
4. Translational Research Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5. Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
6. Cancer Center, Division of General and Gastroenterological Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
7. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
# These authors contributed equally to this study and share first authorship.

Abstract

The overexpression of HER2/neu and EGFR receptors plays important roles in tumorigenesis and tumor progression. Targeting these two receptors simultaneously can have a more widespread application in early diagnosis of cancers. In this study, a new multifunctional nanoparticles (MnMEIO-CyTE777-(Bis)-mPEG NPs) comprising a manganese-doped iron oxide nanoparticle core (MnMEIO), a silane-amino functionalized poly(ethylene glycol) copolymer shell, a near infrared fluorescence dye (CyTE777), and a covalently conjugated anti-HER2/neu and anti-EGFR receptors bispecific antibody (Bis) were successfully developed. In vitro T2-weighted MR imaging studies in SKBR-3 and A431 tumor cells incubated with MnMEIO-CyTE777-(Bis)-mPEG NPs showed - 94.8 ± 3.8 and - 84.1 ± 2.8% negative contrast enhancement, respectively. Pharmacokinetics study showed that MnMEIO-CyTE777-(Bis)-mPEG NPs were eliminated from serum with the half-life of 21.3 mins. In vivo MR imaging showed that MnMEIO-CyTE777-(Bis)-mPEG NPs could specifically and effectively target to HER2/neu- and EGFR-expressing tumors in mice; the relative contrast enhancements were 11.8 (at 2 hrs post-injection) and 61.5 (at 24 hrs post-injection) fold higher in SKBR-3 tumors as compared to Colo-205 tumors. T2-weighted MR and optical imaging studies revealed that the new contrast agent (MnMEIO-CyTE777-(Bis)-mPEG NPs) could specifically and effectively target to HER2/neu- and/or EGFR-expressing tumors. Our results demonstrate that MnMEIO-CyTE777-(Bis)-mPEG NPs are able to recognize the tumors expressing both HER2/neu and/or EGFR, and may provide a novel molecular imaging tool for early diagnosis of cancers expressing HER2/neu and/or EGFR.

Keywords: bispecific antibody, MnMEIO, magnetic resonance imaging, HER2/neu, EGFR.

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How to cite this article:
Wu SC, Chen YJ, Wang HC, Chou MY, Chang TY, Yuan SS, Chen CY, Hou MF, Hsu JTA, Wang YM. Bispecific Antibody Conjugated Manganese-Based Magnetic Engineered Iron Oxide for Imaging of HER2/neu- and EGFR-Expressing Tumors. Theranostics 2016; 6(1):118-130. doi:10.7150/thno.13069. Available from http://www.thno.org/v06p0118.htm