Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7.
Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7.
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DOI：
10.1007/s10585-011-9403-y
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发表时间：
2011-12
影响因子：
4
通讯作者：
Mentlein, Rolf
中科院分区：
文献类型：
--
作者：
Meincke, Manuela;Tiwari, Sanjay;Hattermann, Kirsten;Kalthoff, Holger;Mentlein, Rolf
趋化因子CXCL12/基质细胞衍生因子 - 1及其受体CXCR4和CXCR7在肿瘤侵袭、增殖和转移中起主要作用。由于这两种受体在不同的肿瘤细胞以及肿瘤血管系统中均过度表达，我们评估了它们作为分子成像检测癌症靶点的潜力。我们合成了CXCL12与近红外（NIR）荧光染料IRDye®800CW的偶联物，测试了它们在体外的选择性、敏感性和生物活性以及在体内可视化肿瘤的可行性。纯化的CXCL12偶联物在体外可检测到少至500个仅表达CXCR7或同时表达CXCR4和CXCR7的A764人胶质瘤细胞或MCF - 7乳腺癌细胞。结合具有时间和浓度依赖性，并且标记可被天然肽竞争性取代。与牛血清白蛋白或乳清蛋白的对照偶联物无法标记细胞。在小鼠体内，偶联物迅速分布。在1 - 92小时后，能够高灵敏度地检测到免疫缺陷小鼠体内人MCF - 7和A764细胞的皮下肿瘤。在最初24小时内尤其在肝脏中观察到背景信号，而且颅骨和后肢也产生了一些背景信号。总体而言，荧光CXCL12偶联物是通过靶向肿瘤细胞和肿瘤血管系统来检测实体瘤和转移性肿瘤的灵敏且具有选择性的探针。
本文的网络版（doi:10.1007/s10585 - 011 - 9403 - y）包含补充材料，授权用户可获取。
The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1–92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature. The online version of this article (doi:10.1007/s10585-011-9403-y) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Nimmagadda S;Pullambhatla M;Stone K;Green G;Bhujwalla ZM;Pomper MG
通讯作者：
Pomper MG
影响因子：
8
作者：
Oxmann, D.;Held-Feindt, J.;Mentlein, R.
通讯作者：
Mentlein, R.
影响因子：
3.5
作者：
Hattermann, Kirsten;Ludwig, Andreas;Mentlein, Rolf
通讯作者：
Mentlein, Rolf
影响因子：
11.2
作者：
Chen, XY;Conti, PS;Moats, RA
通讯作者：
Moats, RA
影响因子：
9.3
作者：
Misra, Preeti;Lebeche, Djarnel;Frangioni, John V.
通讯作者：
Frangioni, John V.