Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI.
Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI.
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DOI：
10.1021/acs.bioconjchem.6b00719
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发表时间：
2017-04-19
影响因子：
4.7
通讯作者：
Lu ZR
中科院分区：
文献类型：
--
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
准确的检测和风险分层对于前列腺癌的临床治疗至关重要。目前的诊断方法，包括前列腺特异性抗原(PSA)筛查，无法区分高危肿瘤和低危肿瘤，导致过度诊断和过度治疗。合成了一种针对肿瘤微环境中癌蛋白的多肽靶向造影剂ZD2-Gd(HP-DO3A)EDB-FN，用于侵袭性前列腺癌的非侵袭性检测和表征。EDB-FN是癌胎儿纤维连接蛋白的一个亚型，参与肿瘤上皮向间充质转化(EMT)，参与耐药和转移。转移性PC3细胞中EDB-FN基因的表达水平至少是非转移性LNCaP细胞的3倍。免疫印迹分析显示，在肿瘤中，EDB-FN蛋白在PC3肿瘤移植瘤中高表达，而在LNCaP肿瘤中不表达。在注射后30min内，ZD2-Gd(HP-DO3A)在PC3肿瘤的增强MRI中产生的对比度噪声比是LNCaP肿瘤的两倍以上。ZD2-Gd(HP-DO3A)具有较高的抗金属离子迁移能力和最小的组织蓄积能力。我们的结果表明，EDB-FN和ZD2-Gd(HP-DO3A)的分子MRI可以潜在地用于前列腺癌的非侵入性检测和风险分层。将这种靶向造影剂结合到现有的临床增强MRI程序中，有可能提高前列腺癌的诊断准确性。
Accurate detection and risk stratification are paramount to the clinical management of prostate cancer. Current diagnostic methods, including prostate specific antigen (PSA) screening, are unable to differentiate high-risk tumors from low-risk tumors, resulting in overdiagnosis and overtreatment. A peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, was synthesized for non-invasive detection and characterization of aggressive prostate cancer. EDB-FN, one of the subtypes of oncofetal fibronectin, is involved in tumor epithelial-to-mesenchymal transition (EMT), which is implicated in drug resistance and metastasis. The EDB-FN mRNA level in the metastatic PC3 cells was at least three times higher than that in non-metastatic LNCaP cells. In tumors, EDB-FN protein was highly expressed in PC3 tumor xenografts, but not in LNCaP tumors, as revealed by western blot analysis. ZD2-Gd(HP-DO3A) produced over two times higher contrast-to-noise ratio in the PC3 tumors than in the LNCaP tumors in contrast-enhanced MRI during 30 min after injection. ZD2-Gd(HP-DO3A) possessed high chelate stability against transmetallation and minimal tissue accumulation. Our results demonstrate that molecular MRI of EDB-FN with ZD2-Gd(HP-DO3A) can potentially be used for non-invasive detection and risk stratification of human prostate cancer. Incorporation of this targeted contrast agent in the existing clinical contrast enhanced MRI procedures has the potential to improve diagnostic accuracy of prostate cancer.
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影响因子：
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