Introduction: Integrin α 6 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 α 6-targeted peptide, we developed an optimized integrin α 6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice.
Materials and Methods: 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.
Results: The R₁ relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM^{− 1}s^{− 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.
Conclusion: These findings suggest the potential application of this integrin α 6-targeted MR probe for the detection of HCC, particularly for small HCC.
Graphical abstract:

Keywords: magnetic resonance, integrin α 6, hepatocellular carcinoma, peptide, probe


中文翻译：

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用于小鼠肝细胞癌分子成像的优化整合素 α6 靶向磁共振探针

简介：整合素α 6 是一种有吸引力的肝细胞癌 (HCC) 分子成像诊断生物标志物，因为它在临床早期 HCC 中具有极高的阳性率（约 94%）。在这项研究中，基于我们之前确定的整合素 α 6 靶向肽，我们开发了一种优化的整合素 α 6 靶向磁共振 (MR) 探针，称为 DOTA(Gd)-ANADYWR，用于小鼠 HCC 的 MR 成像。
材料和方法：在 3.0 T MR 系统上测量 DOTA(Gd)-ANADYWR的纵向 (R ₁ ) 弛豫率。在四种不同的小鼠模型中研究了该试剂的特定肿瘤增强作用，包括皮下、原位、基因工程和化学诱导的 HCC 小鼠。
结果： R ₁DOTA(Gd)-ANADYWR 的弛豫值为 5.11 mM ^{- 1} s ^{- 1} at 3.0 T，与非特异性临床药物 Gadoteridol 的弛豫值相似。DOTA(Gd)-ANADYWR 在 HCC 病变中产生优异的增强 MR 信号，并为临床可用的肝胆 MR 造影剂钆塞酸二钠 (Gd-EOB-DTPA) 提供互补的增强 MR 信号。重要的是，DOTA(Gd)-ANADYWR 可以有效地可视化临床 Gd-EOB-DTPA 难以检测到的小 HCC 病变（约 1 毫米）。
结论：这些发现表明这种整合素 α 6 靶向 MR 探针在检测 HCC 中的潜在应用，特别是对于小 HCC。
图形摘要：

关键词： 磁共振，整合素α6，肝细胞癌，肽，探针