Optical fiber-based in vivo quantification of growth factor receptors.
Optical fiber-based in vivo quantification of growth factor receptors.
复制标题
基于光纤的生长因子受体体内定量。
DOI：
10.1002/cncr.26487
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发表时间：
2012
期刊：
影响因子：
6.2
通讯作者：
BakerJr,JamesR
中科院分区：
文献类型：
--
作者：
Thomas,ThommeyP;Chang,Yu-Chung;Ye,JingYong;Kotlyar,Alina;Cao,Zhengyi;Shukla,Rameshwer;Qin,Suyang;Norris,TheodoreB;BakerJr,JamesR
生长因子受体如表皮生长因子受体1和人表皮生长受体2 （HER2）在某些癌细胞中过度表达。抗这些受体的抗体(如：西妥昔单抗和妥珠单抗[赫赛汀])在癌症治疗中显示出治疗价值。现有的肿瘤中这些受体的定量方法包括免疫组织化学或DNA定量，都是在提取的组织样本中。这项研究的目的是评估一种基于光纤的技术是否可以同时用于量化多种生长因子受体的表达。方法作者使用单克隆抗体曲妥珠单抗作为靶向配体来检测HER2表达。他们将曲妥珠单抗与2种不同的Alexa荧光染料结合，具有不同的激发和发射波长。随后将两种染料偶联物静脉注射到携带HER2‐表达皮下肿瘤的小鼠体内。然后通过30号针头将光纤插入肿瘤，并使用单束激光束作为激发源，通过2光子光纤荧光识别和量化2共轭物发出的荧光。结果2偶联物以受体特异性的方式竞争性地结合到表达HER2的肿瘤上，但它们不能结合到不表达HER2的类似细胞肿瘤上。通过2光子光纤荧光测定的肿瘤中共轭物的浓度可作为HER2表达水平的指标。结论本研究为同时定量肿瘤受体提供了一种微创技术。癌症2012;。©2011美国癌症协会。
BACKGROUNDGrowth factor receptors such as epidermal growth factor receptor 1 and human epidermal growth receptor 2 (HER2) are overexpressed in certain cancer cells. Antibodies against these receptors (eg. cetuximab and transtuzumab [Herceptin]) have shown therapeutic value in cancer treatment. The existing methods for the quantification of these receptors in tumors involve immunohistochemistry or DNA quantification, both in extracted tissue samples. The goal of the study was to evaluate whether an optical fiber‐based technique can be used to quantify the expression of multiple growth factor receptors simultaneously.METHODSThe authors examined HER2 expression using the monoclonal antibody trastuzumab as a targeting ligand to test their system. They conjugated trastuzumab to 2 different Alexa Fluor dyes with different excitation and emission wavelengths. Two of the dye conjugates were subsequently injected intravenously into mice bearing HER2‐expressing subcutaneous tumors. An optical fiber was then inserted into the tumor through a 30‐gauge needle, and using a single laser beam as the excitation source, the fluorescence emitted by the 2 conjugates was identified and quantified by 2‐photon optical fiber fluorescence.RESULTSThe 2 conjugates bound to the HER2‐expressing tumor competitively in a receptor‐specific fashion, but they failed to bind to a similar cell tumor that did not express HER2. The concentration of the conjugate present in the tumor as determined by 2‐photon optical fiber fluorescence was shown to serve as an index of the HER2 expression levels.CONCLUSIONSThese studies offer a minimally invasive technique for the quantification of tumor receptors simultaneously. Cancer 2012;. © 2011 American Cancer Society.