An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice.
An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice.
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DOI：
10.2147/jhc.s312921
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发表时间：
2021
影响因子：
4.1
通讯作者：
Feng GK
中科院分区：
文献类型：
--
作者：
Lin BQ;Zhang WB;Zhao J;Zhou XH;Li YJ;Deng J;Zhao Q;Fu G;Xie CM;Xu YK;Feng GK
整合素α6在临床早期肝细胞癌（HCC）中具有极高的阳性率（约94%），是一种有吸引力的分子影像学诊断标志物。在这项研究中，基于我们先前鉴定的整合素α6靶向肽，我们开发了一种优化的整合素α6靶向磁共振（MR）探针，称为DOTA（Gd）-ANADYWR，用于小鼠肝癌的MR成像。在3.0T磁共振系统上测量了DOTA（Gd）-ANADYWR的纵向弛豫率（R1）。在四种不同的小鼠模型中研究了该试剂的特异性肿瘤增强作用，包括皮下、原位、基因工程和化学诱导的HCC小鼠。DOTA（Gd）-ANADYWR在3.0 T下的R1弛豫率值为5.11 mM− 1 s −1，与非特异性临床药物Gadoteridol相似。DOTA（Gd）-ANADYWR在HCC病变中产生上级增强MR信号，并提供与临床可用的肝胆MR造影剂钆塞酸二钠（Gd-EOB-DTPA）互补的增强MR信号。重要的是，DOTA（Gd）-ANADYWR可以有效地显示小的HCC病变（约1 mm），这是临床Gd-EOB-DTPA很难检测到的。这些发现表明这种整合素α6靶向MR探针在检测HCC，特别是小HCC中的潜在应用。
Integrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice. The longitudinal (R1) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system . The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice. The R1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM−1s−1 at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (Gd-EOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA. These findings suggest the potential application of this integrin α6-targeted MR probe for the detection of HCC, particularly for small HCC.