Magnetic Resonance Molecular Imaging of Extradomain B Fibronectin Improves Imaging of Pancreatic Cancer Tumor Xenografts.
Magnetic Resonance Molecular Imaging of Extradomain B Fibronectin Improves Imaging of Pancreatic Cancer Tumor Xenografts.
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DOI：
10.3389/fonc.2020.586727
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发表时间：
2020
影响因子：
4.7
通讯作者：
Lu ZR
中科院分区：
文献类型：
--
作者：
Qiao P;Ayat NR;Vaidya A;Gao S;Sun W;Chou S;Han Z;Gilmore H;Winter JM;Lu ZR
胰腺癌患者的生存可以大大提高，如果他们的疾病是在早期发现，可能治愈的阶段。癌蛋白的磁共振分子成像（MRMI）是一种有前途的策略，准确，早期发现的疾病。在这里，我们测试的假设，MRMI的extradomain-B纤连蛋白（EDB-FN），在肿瘤细胞外基质中丰富的癌蛋白，可以克服胰腺癌的间质屏障，以促进有效的分子成像和小肿瘤的检测。用肽-荧光团缀合物（ZD 2-Cy5.5）对正常、癌前和恶性人胰腺组织的样本进行染色以评估EDB-FN结合和表达。在三种携带人胰腺癌异种移植物的鼠模型中进行了具有EDB-FN特异性的ZD 2-N3-Gd（HP-DO 3A）（MT 218）的MRMI和具有Gd（HP-DO 3A）的MRI，包括Capan-1侧腹模型、BxPC 3-GFP-Luc和PANC-1-GFP-Luc胰腺内异种移植物模型。分析比较两种造影剂的肿瘤增强效果。用ZD 2-Cy5.5染色人组织样品显示EDB-FN在胰腺肿瘤中高表达，在癌前组织中中等表达，在正常组织中几乎不表达。使用MT 218的MRMI产生了强大的肿瘤内对比，清楚地检测和描绘了小肿瘤（最小平均尺寸：6.1 mm 2），并且优于使用Gd的常规对比增强MRI（HP-DO 3A）。信号增强的定量分析显示，MT 218在Capan-1侧腹、BxPC 3-GFP-Luc和PANC-1-GFP-Luc胰腺内模型中分别产生比临床药剂高2.7、2.1和1.6倍的对比噪声比（CNR）（p < 0.05）。ECM癌蛋白EDB-FN与MT 218的MRMI能够在小胰腺肿瘤中产生上级对比增强，并在动物模型中提供准确的肿瘤描绘。早期，准确的检测和描绘胰腺癌的高分辨率MRMI有可能指导及时治疗，并显着提高胰腺癌患者的长期生存。
The survival of pancreatic cancer patients can be greatly improved if their disease is detected at an early, potentially curable stage. Magnetic resonance molecular imaging (MRMI) of oncoproteins is a promising strategy for accurate, early detection of the disease. Here, we test the hypothesis that MRMI of extradomain-B fibronectin (EDB-FN), an abundant oncoprotein in the tumor extracellular matrix, can overcome the stromal barriers of pancreatic cancer to facilitate effective molecular imaging and detection of small tumors. Specimens of normal, premalignant, and malignant human pancreatic tissues were stained with a peptide-fluorophore conjugate (ZD2-Cy5.5) to assess EDB-FN binding and expression. MRMI with ZD2-N3-Gd(HP-DO3A) (MT218) specific to EDB-FN and MRI with Gd(HP-DO3A) were performed in three murine models bearing human pancreatic cancer xenografts, including a Capan-1 flank model, a BxPC3-GFP-Luc and a PANC-1-GFP-Luc intrapancreatic xenograft model. Tumor enhancement of the contrast agents was analyzed and compared. Staining of human tissue samples with ZD2-Cy5.5 revealed high EDB-FN expression in pancreatic tumors, moderate expression in premalignant tissue, and little expression in normal tissue. MRMI with MT218 generated robust intratumoral contrast, clearly detected and delineated small tumors (smallest average size: 6.1 mm2), and out-performed conventional contrast enhanced MRI with Gd(HP-DO3A). Quantitative analysis of signal enhancement revealed that MT218 produced 2.7, 2.1, and 1.6 times greater contrast-to-noise ratio (CNR) than the clinical agent in the Capan-1 flank, BxPC3-GFP-Luc and PANC-1-GFP-Luc intrapancreatic models, respectively (p < 0.05). MRMI of the ECM oncoprotein EDB-FN with MT218 is able to generate superior contrast enhancement in small pancreatic tumors and provide accurate tumor delineation in animal models. Early, accurate detection and delineation of pancreatic cancer with high-resolution MRMI has the potential to guide timely treatment and significantly improve the long-term survival of pancreatic cancer patients.
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影响因子：
4.9
作者：
Li Y;Han Z;Roelle S;DeSanto A;Sabatelle R;Schur R;Lu ZR
通讯作者：
Lu ZR
纤连蛋白，原纤维生成和体内功能。
影响因子：
7.2
作者：
Schwarzbauer JE;DeSimone DW
通讯作者：
DeSimone DW
影响因子：
4.7
作者：
Ayat, Nadia R.;Vaidya, Amita;Lu, Zheng-Rong
通讯作者：
Lu, Zheng-Rong
细胞外基质和胰腺癌：一种复杂的关系。
影响因子：
5.2
作者：
Weniger M;Honselmann KC;Liss AS
通讯作者：
Liss AS
影响因子：
4.7
作者：
Han Z;Li Y;Roelle S;Zhou Z;Liu Y;Sabatelle R;DeSanto A;Yu X;Zhu H;Magi-Galluzzi C;Lu ZR
通讯作者：
Lu ZR