Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer.
Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer.
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DOI：
10.1021/bc300009t
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发表时间：
2012-08-15
影响因子：
4.7
通讯作者：
Lu, Zheng-Rong
中科院分区：
文献类型：
--
作者：
Wu, Xueming;Burden-Gulley, Susan M.;Yu, Guan-Ping;Tan, Mingqian;Lindner, Daniel;Brady-Kalnay, Susann M.;Lu, Zheng-Rong
肿瘤细胞外基质中含有丰富的肿瘤相关蛋白，可作为肿瘤分子成像的生物标志物。针对这些生物标志物的安全有效的靶向造影剂的创新设计和开发将使高空间分辨率的有效MR癌症分子成像成为可能。在这项研究中，我们合成了一种针对肿瘤间质中凝结的血浆蛋白的Gd(III)螯合物CLT1-dL-(Gd-DOTA)4的低分子量CLT1多肽，用于肿瘤MR分子成像。通过第一代赖氨酸树枝状大分子将四个Gd-DOTA单胺螯合物偶联到一个CLT1多肽上，合成了CLT1-dL-(Gd-DOTA)4。在37℃和1.5T下，CLT1-dL-(Gd-DOTA)4的松弛系数为40.4 mM−1S−1/分子(10.1 mM−1S−1/Gd)。在0.03mmolGd/kg剂量下，该造影剂可提高荷瘤裸鼠PC3前列腺癌的对比度。多肽靶向磁共振造影剂有望用于前列腺癌的高分辨率磁共振分子成像。
Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecular imaging. CLT1-dL-(Gd-DOTA)4 was synthesized by conjugating four Gd-DOTA monoamide chelates to a CLT1 peptide via generation 1 lysine dendrimer. The T1 relaxivity of CLT1-dL-(Gd-DOTA)4 was 40.4 mM−1s−1 per molecule (10.1 mM−1s−1 per Gd) at 37 °C and 1.5 T. Fluorescence imaging showed high binding specificity of CLT1 to orthotopic PC3 prostate tumor in mice. The contrast agent resulted in improved tumor contrast enhancement in male athymic nude mice bearing orthotopic PC3 prostate tumor xenograft at a dose of 0.03 mmol Gd/kg. The peptide targeted MRI contrast agent is promising for high-resolution MR molecular imaging of prostate tumor.
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DOI：
10.1007/s00259-008-0829-7
发表时间：
2008-08-01
影响因子：
9.1
作者：
Lucignani, Giovanni
通讯作者：
Lucignani, Giovanni
影响因子：
4.8
作者：
Burden-Gulley, Susan M.;Gates, Theresa J.;Brady-Kalnay, Susann M.
通讯作者：
Brady-Kalnay, Susann M.
影响因子：
2.2
作者：
Maurer, Alan H.
通讯作者：
Maurer, Alan H.
影响因子：
3.3
作者：
Lipinski, Michael J.;Amirbekian, Vardan;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.
DOI：
10.1073/pnas.0606281104
发表时间：
2007-01-16
影响因子：
11.1
作者：
Amirbekian, Vardan;Lipinski, Michael J.;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.