Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI.
Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI.
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DOI：
10.1016/j.biomaterials.2013.06.057
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发表时间：
2013-10
期刊：
影响因子：
14
通讯作者：
Lu, Zheng-Rong
中科院分区：
文献类型：
--
作者：
Zhou, Zhuxian;Wu, Xueming;Kresak, Adam;Griswold, Mark;Lu, Zheng-Rong
合理设计和开发与肿瘤相关蛋白结合的靶向造影剂，将有助于磁共振成像技术更准确地诊断和预测肿瘤预后。CREKA是一种肿瘤归巢的五肽（Cys-Arg-Glu-Lys-Ala），特异地归巢在肿瘤微环境中大量表达的纤维蛋白-纤维连接蛋白复合物。在这项研究中，我们开发并评估了CREKA肽靶向的多路Gd-MR探针（CREKA- tris - gd (DOTA)）用于乳腺肿瘤的MR成像。通过巯基-马来酰亚胺和叠氮化物-炔的键合反应，将CREKA和含Gd（III）的叠氮化物分别附着在马来酰亚胺-三烷基骨架上。CREKA-Tris-Gd（DOTA）结构明确，分子量为2914 Da。在室温和3t下，CREKA- tris -Gd（DOTA）的T1松弛度为8.06 mM-1s-1 / Gd（24.18 mM-1s-1 /分子），荧光成像显示CREKA对小鼠4T1乳腺肿瘤模型具有较高的结合特异性，而对重组后的CREKA （CERAK）则没有这种结合特异性。当剂量为0.1 mmol Gd/kg时，CREKA肽靶向造影剂比相应的CERAK造影剂和商业化造影剂Prohance™在携带4T1乳腺癌异种移植的雌性胸腺小鼠肿瘤中的造影剂增强效果更强。这种小分子造影剂经显像显示毒性低，容易从体内排出。靶向MRI造影剂具有MRI特异性肿瘤分子成像的潜力。
Rational design and develop of targeted contrast agents binding to cancer-related proteins will achieve more accurate cancer diagnosis and prognosis by magnetic resonance (MR) imaging. CREKA is a tumor-homing pentapeptide (Cys-Arg-Glu-Lys-Ala) specifically homes to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment. In this study, we developed and evaluated a CREKA peptide targeted multiplexed Gd-MR probe (CREKA-Tris-Gd(DOTA)) for MR imaging of breast tumors. CREKA and azide bearing Gd(III) was attached to a maleimide-functional trialkyne scaffold via thiol-maleimide and azide-alkyne click chemistry, respectively. CREKA-Tris-Gd(DOTA) has a well-defined structure with a molecular weight of 2914 Da. The T1 relaxivity of CREKA-Tris-Gd(DOTA) is 8.06 mM-1s-1 per Gd (24.18 mM-1s-1 per molecule) at room temperature and 3 T. Fluorescence imaging showed high binding specificity of CREKA to a 4T1 breast tumor model in mice while it was not found for the scrambled CREKA (CERAK). The CREKA peptide-targeted contrast agent resulted in greater contrast enhancement than the corresponding CERAK agent and the commercialized contrast agent Prohance™ in tumor at a dose of 0.1 mmol Gd/kg in female athymic mice bearing 4T1 breast carcinoma xenograft. This small molecular contrast agent was easily excreted from body after imaging indicated low toxicity. The targeted MRI contrast agent has a potential for specific cancer molecular imaging with MRI.
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影响因子：
3.2
作者：
Lu, Zheng-Rong;Wu, Xueming
通讯作者：
Wu, Xueming
影响因子：
6.7
作者：
White, GW;Gibby, WA;Tweedle, MF
通讯作者：
Tweedle, MF
影响因子：
7.3
作者：
Boros, Eszter;Caravan, Peter
通讯作者：
Caravan, Peter
DOI：
10.1073/pnas.0610298104
发表时间：
2007-01-16
影响因子：
11.1
作者：
Simberg, Dmitri;Duza, Tasmia;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki
影响因子：
14
作者：
Liu, Yongjun;Chen, Zhijin;Zhang, Na
通讯作者：
Zhang, Na