Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes

Jinfeng Liu; Yihan Chen; Guohua Wang; Qing Lv; Yali Yang; Jing Wang; Pingyu Zhang; Jie Liu; Yu Xie; Li Zhang; Mingxing Xie

doi:10.1016/j.biomaterials.2018.02.017

Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes

Biomaterials. 2018 Apr:162:200-207. doi: 10.1016/j.biomaterials.2018.02.017. Epub 2018 Feb 8.

Authors

Jinfeng Liu¹, Yihan Chen¹, Guohua Wang², Qing Lv¹, Yali Yang¹, Jing Wang¹, Pingyu Zhang¹, Jie Liu¹, Yu Xie¹, Li Zhang³, Mingxing Xie⁴

Affiliations

¹ Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging.
² Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430222, China.
³ Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging. Electronic address: zli429@hust.edu.cn.
⁴ Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging. Electronic address: xiemx64@126.com.

PMID: 29453053
DOI: 10.1016/j.biomaterials.2018.02.017

Abstract

Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB_CD3) or isotype antibody (NB_con) were prepared and characterized. There was significant adhesion of NB_CD3 to T lymphocytes compared with NB_conin vitro. The signal intensity of the adherent NB_CD3 was significantly higher than that of the NB_con in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NB_CD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NB_CD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation.

Keywords: Heart transplantation; Rejection; T lymphocyte; Ultrasound molecular imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Graft Rejection
Heart Transplantation
Male
Molecular Imaging / methods
Nanostructures / chemistry*
Rats
T-Lymphocytes / metabolism*
Transplantation, Homologous
Ultrasonography / methods*