Zhao Ping, Zhao Shuai, Zhang Jiaqi, Lai Manlin, Sun Litao, Yan Fei
Department of Ultrasound, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
Department of Ultrasound, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Suzhou 234000, China.
Pharmaceutics. 2022 Sep 8;14(9):1898. doi: 10.3390/pharmaceutics14091898.
Osteonecrosis of the femoral head (ONFH) is a disease that is commonly seen in the clinic, but its detection rate remains limited, especially at the early stage. We developed an ultrasound molecular imaging (UMI) approach for early diagnosis of ONFH by detecting the expression of integrin αvβ3 during the pathological changes in steroid-induced osteonecrosis of the femoral head (SIONFH) in rat models. The integrin αvβ3-targeted PLGA or lipid microbubbles modified with iRGD peptides were fabricated and characterized. Their adhesion efficiency to mouse brain microvascular endothelial cells in vitro was examined, and the better LIPOiRGD was used for further in vivo molecular imaging of SIONFH rats at 1, 3 and 5 weeks; revealing significantly higher UMI signals could be observed in the 3-week and 5-week SIONFH rats but not in the 1-week SIONFH rats in comparison with the non-targeted microbubbles (32.75 ± 0.95 vs. 0.17 ± 0.09 for 5 weeks, p < 0.05; 5.60 ± 1.31 dB vs. 0.94 ± 0.81 dB for 3 weeks, p < 0.01; 1.13 ± 0.13 dB vs. 0.73 ± 0.31 dB for 1 week, p > 0.05). These results were consistent with magnetic resonance imaging data and confirmed by immunofluorescence staining experiments. In conclusion, our study provides an alternative UMI approach to the early evaluation of ONFH.
股骨头坏死（ONFH）是临床上常见的疾病，但其检出率仍然有限，尤其是在早期阶段。我们开发了一种超声分子成像（UMI）方法，通过检测大鼠模型中类固醇诱导的股骨头坏死（SIONFH）病理变化过程中整合素αvβ3的表达来早期诊断ONFH。制备并表征了用iRGD肽修饰的靶向整合素αvβ3的聚乳酸-羟基乙酸共聚物（PLGA）或脂质微泡。检测了它们在体外对小鼠脑微血管内皮细胞的黏附效率，并使用性能更好的脂质-整合素αvβ3靶向微泡（LIPOiRGD）对SIONFH大鼠在第1、3和5周进行进一步的体内分子成像；结果显示，与非靶向微泡相比，在3周和5周的SIONFH大鼠中可观察到显著更高的UMI信号，但在1周的SIONFH大鼠中未观察到（5周时为32.75±0.95 vs. 0.17±0.09，p<0.05；3周时为5.60±1.31 dB vs. 0.94±0.81 dB，p<0.01；1周时为1.13±0.13 dB vs. 0.73±0.31 dB，p>0.05）。这些结果与磁共振成像数据一致，并通过免疫荧光染色实验得到证实。总之，我们的研究为ONFH的早期评估提供了一种替代性的UMI方法。
