Xu Jia, Deng Cheng, Gao Tang, He Mengrong, Fu Wenpei, Zhang Xin, Bai Yin, Qiu Jiani, Wang Rui, Chen Yihan, Jin Qiaofeng, Zhang Li, Lv Qing, Xie Mingxing, Wu Wenqian
Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Clinical Research Center for Medical Imaging in Hubei Province, Wuhan, 430022, China.
J Nanobiotechnology. 2025 Aug 22;23(1):581. doi: 10.1186/s12951-025-03672-9.
Chronic rejection (CR) remains the leading cause of morbidity and mortality in heart transplantation survivors. The primary pathological features of CR encompass cardiac allograft vasculopathy and myocardial fibrosis. Currently, its diagnosis heavily relies on invasive procedures, underscoring the pressing need for non-invasive evaluation methods. This study introduces a novel approach utilizing mannose-modified microbubbles (MB) targeting CD206 (mannose receptor) positive M2 macrophages for early CR detection. In vitro experiments demonstrate substantial adhesion of MB to M2 macrophages compared to common microbubbles (MB). In a CR rat model, MB and MB are administered at three distinct time points (2 weeks, 4 weeks, and 6 weeks), followed by contrast-enhanced ultrasound images and quantitative analysis using the ultrasound destruction-supplementation method. Starting at 2 weeks and continuing through 6 weeks, MB demonstrates significantly higher signal intensity than MB in allograft rats. However, this difference is not observed in isograft rats at any of the indicated time points. These findings suggest an increase in M2 macrophage infiltration in allografts compared to isografts. Furthermore, the signal intensity of MB positively correlates with the percentage of CD206 in allograft rats. This study proposes a promising approach, simultaneous noninvasive ultrasound molecular imaging, for the early-stage evaluation of CR.
慢性排斥反应（CR）仍然是心脏移植幸存者发病和死亡的主要原因。CR的主要病理特征包括心脏移植血管病变和心肌纤维化。目前，其诊断严重依赖侵入性检查，这凸显了对非侵入性评估方法的迫切需求。本研究引入了一种新方法，利用靶向CD206（甘露糖受体）阳性M2巨噬细胞的甘露糖修饰微泡（MB）进行CR的早期检测。体外实验表明，与普通微泡（MB）相比，MB对M2巨噬细胞有大量黏附。在CR大鼠模型中，在三个不同时间点（2周、4周和6周）给予MB和MB，随后使用超声破坏补充法进行对比增强超声成像和定量分析。从2周开始一直到6周，在同种异体移植大鼠中，MB的信号强度显著高于MB。然而，在同基因移植大鼠的任何指定时间点均未观察到这种差异。这些发现表明，与同基因移植相比，同种异体移植中M2巨噬细胞浸润增加。此外，在同种异体移植大鼠中，MB的信号强度与CD206的百分比呈正相关。本研究提出了一种有前景的方法，即同步非侵入性超声分子成像，用于CR的早期评估。
