Ultrasound Molecular Imaging of Acute Cellular Cardiac Allograft Rejection in Rat With T-Cell–Specific Nanobubbles
Ultrasound Molecular Imaging of Acute Cellular Cardiac Allograft Rejection in Rat With T-Cell–Specific Nanobubbles
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DOI：
10.1097/tp.0b013e31829b759f
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Wei Wu;Zhe Zhang;Lisha Zhuo;Lina Zhou;Ping Liu;Yun He;Yunhua Gao;Rui Li;Qinghai Chen;Xing Hua
中科院分区：
文献类型：
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作者：
Wei Wu;Zhe Zhang;Lisha Zhuo;Lina Zhou;Ping Liu;Yun He;Yunhua Gao;Rui Li;Qinghai Chen;Xing Hua
研究背景急性排斥反应（AR）是心脏移植的主要障碍之一，但目前尚无一种能反映其病理本质的无创性诊断方法。本研究制备了一种靶向活化T细胞的特异性纳米气泡，并将其应用于心肌声学造影（MCE）对心脏移植中AR的超声分子成像。方法制备载抗CD 25抗体（NB特异性）或同种型对照抗体（NB非特异性）的纳米气泡，应用于大鼠模型的超声分子成像。在24例同种异体移植物和18例同系移植物中进行MCE，分为三组，包括移植后2，4和6天。共聚焦激光扫描显微镜用于评估纳米气泡和T细胞在四个同种异体移植物和四个同种异体移植物中的结合。结果同种异体移植物NB-MCE呈“延迟强化”，时间-强度曲线呈第二峰。第二峰强度和时间与移植时间和AR病理分级呈正相关（P <0.01）。激光共聚焦扫描显微镜显示，心肌声学造影后，纳米气泡与心肌中的淋巴细胞结合，具有NB特异性。结论以T细胞为靶点的纳米气泡微球声学造影可用于心脏移植术后AR的超声分子成像。延迟强化的出现提示AR的发生，时间-强度曲线上第二峰的强度和时间为AR的诊断和严重程度提供了潜在的定量指标。
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 (NBspecific) or isotype control antibody (NBnonspecific) 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 NBspecific 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 NBspecific. 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.