Ultrasound Molecular Imaging as a Potential Non-invasive Diagnosis to Detect the Margin of Hepatocarcinoma via CSF-1R Targeting
Ultrasound Molecular Imaging as a Potential Non-invasive Diagnosis to Detect the Margin of Hepatocarcinoma via CSF-1R Targeting
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超声分子成像作为一种潜在的非侵入性诊断，通过 CSF-1R 靶向检测肝癌边缘
DOI：
10.3389/fbioe.2020.00783
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发表时间：
2020-07-14
影响因子：
5.7
通讯作者：
Luo, Baoming
中科院分区：
文献类型：
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作者：
Jiang, Qiongchao;Zeng, Yunting;Luo, Baoming
虽然射频消融（RFA）被认为是治疗肝细胞癌（HCC）的有效方法，但仍有超过30%的患者存在RFA（IRFA）不足的情况，这会促使残留肿瘤更具侵袭性。一种可能的解决方法是准确识别HCC的边缘。集落刺激因子1受体（CSF-1 R）被发现在肿瘤相关巨噬细胞（TAM）和单核细胞中特异性表达，且更倾向于定位于HCC的边缘。利用生物素化方法，我们开发了CSF-1 R-缀合的纳米气泡CSF-1 R（NBCSF-1 R），使用薄膜水化方法用于HCC的边缘检测。巨噬细胞中CSF-1 R的表达高于HCC细胞系。免疫荧光显示CSF-1 R主要分布于异种移植瘤和IFRA模型的边缘。在体外，NBCSF-1 R是稳定的，即使在储存6个月后也能提供清晰的超声图像。在共培养中，NBCSF-1 R与巨噬细胞的粘附显著优于HCC细胞（p = 0.05）。在体内对比增强超声成像中，NBCSF-1 R的洗脱半衰期显著大于NBCTRL和Sonovue®（p = 0.05）。注射NBCSF-1 R后，肿瘤周围的信号强度高于肿瘤中心或非肿瘤区域。总之，NBCSF-1 R可能被用作HCC边缘检测的非侵入性诊断方式，从而提高RFA的效率。该平台还可以作为RFA后检测残留HCC的补充方法;也可以用于治疗药物或基因的靶向递送。
Though radiofrequency ablation (RFA) is considered to be an effective treatment for hepatocellular carcinoma (HCC), but more than 30% of patients may suffer insufficient RFA (IRFA), which can promote more aggressive of the residual tumor. One possible method to counter this is to accurately identify the margin of the HCC. Colony-stimulating factor 1 receptor (CSF-1R) has been found to be restrictively expressed by tumor associated macrophages (TAMs) and monocytes which more prefer to locate at the boundary of HCC. Using biotinylation method, we developed a CSF-1R-conjugated nanobubble CSF-1R (NBCSF–1R) using a thin-film hydration method for margin detection of HCC. CSF-1R expression was higher in macrophages than in HCC cell lines. Furthermore, immunofluorescence showed that CSF-1R were largely located in the margin of xenograft tumor and IFRA models. In vitro, NBCSF–1R was stable and provided a clear ultrasound image even after being stored for 6 months. In co-culture, NBCSF–1R adhered to macrophages significantly better than HCC cells (p = 0.05). In in vivo contrast-enhanced ultrasound imaging, the washout half-time of the NBCSF–1R was significantly greater than that of NBCTRL and Sonovue® (p = 0.05). The signal intensity of the tumor periphery was higher than the tumor center or non-tumor region after NBCSF–1R injection. Taken together, NBCSF–1R may potentially be used as a non-invasive diagnostic modality in the margin detection of HCC, thereby improving the efficiency of RFA. This platform may also serve as a complement method to detect residual HCC after RFA; and may also be used for targeted delivery of therapeutic drugs or genes.