Ultrasound molecular imaging of acute cellular cardiac allograft rejection in rat with T-cell-specific nanobubbles.
BACKGROUND
Acute rejection (AR) is one of the main obstacles of cardiac transplantation; however, a noninvasive diagnostic method, which reflects its pathologic nature, has not been developed yet. In this study, we prepared a specific nanobubbles targeting to the activated T cells and applied it in the ultrasound molecular imaging of AR in heart transplantation by myocardial contrast echocardiography (MCE).


METHODS
Nanobubbles loading anti-CD25 antibody (NB(specific)) or isotype control antibody (NB(nonspecific)) were prepared and then applied in the ultrasound molecular imaging by MCE in a rat model. MCE was performed in 24 allografts and 18 isografts that were divided into three groups, including days 2, 4, and 6 after transplantation. Confocal laser scanning microscopy was used to evaluate the binding of nanobubbles and T cells in four allografts and four isografts.


RESULTS
MCE with NB(specific) in allograft showed a "delayed enhancement," and the time-intensity curve presented a second peak. The intensity and time of second peak were both positively correlated with the transplant time (P<0.01) and the pathologic grade of AR (P<0.01). Confocal laser scanning microscopy demonstrated the binding of nanobubbles and lymphocytes in myocardium post-MCE with NB(specific).


CONCLUSIONS
Ultrasound molecular imaging of AR after heart transplantation can be achieved by using MCE with the nanobubbles targeted to T cells. The appearance of delayed enhancement indicates the occurrence of AR, and the intensity and time of the second peak in time-intensity curve provide potential quantitative indications for diagnosis and severity of AR.
1 Department of Cardio-Thoracic Surgery, Southwest Hospital, Third Military University, Shapingba, Chongqing, China. 2 Department of Cardiac Surgery, Third Hospital, Peking University, Haidian District, Beijing, China. 3 Department of Ultrasound, Xinqiao Hospital, Third Military University, Shapingba, Chongqing, China. 4 Department of Ultrasound, Southwest Hospital, Third Military University, Shapingba, Chongqing, China. 5 Address correspondence to: Xing Hua, M.D., Department of Ultrasound, Southwest Hospital, Third Military University, Shapingba, Chongqing 400038, P.R. China.
Wei
W
Wu
Zhe
Z
Zhang
Lisha
L
Zhuo
Lina
L
Zhou
Ping
P
Liu
Yun
Y
He
Yunhua
Y
Gao
Rui
R
Li
Qinghai
Q
Chen
Xing
X
Hua
D000208:Acute Disease; D000818:Animals; D000906:Antibodies; D003287:Contrast Media; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods*; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007111:Immunity, Cellular; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000379:methods*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011237:Predictive Value of Tests; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000000981:diagnostic imaging* / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
D000906:Antibodies; D003287:Contrast Media; D053645:Interleukin-2 Receptor alpha Subunit