In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control
In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control
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DOI：
10.1593/neo.08648
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发表时间：
2009-03-01
期刊：
影响因子：
4.8
通讯作者：
Ntziachristos, Vasilis
中科院分区：
文献类型：
--
作者：
Baeten, John;Haller, Jodi;Ntziachristos, Vasilis
乳腺癌的光学成像已被认为是在临床和临床前环境中检测疾病的功能和分子特征。应用于实验室研究，光子研究为临床前成像和药物发现提供了一个高度通用的工具。光学方法的一个特别的优点是多个光谱带用于执行成像的可用性。在这里，我们利用这一特点来证明如何使用不同的波长来提供内部控制，并显着提高分子成像应用中的观察精度。特别是，我们显示了独立的体内检测半胱氨酸蛋白酶沿着与肿瘤的渗透性和间质体积测量使用双波长的方法。为了产生针对临床研究的结果，使用了自发发生乳腺肿瘤的转基因Her 2/neu小鼠模型。体内结果针对常规离体测试如组织学和蛋白质印迹分析进行了验证。通过校正生物分布参数，双波长方法通过将真正的分子靶标与探针生物分布分离来提高分子观察的准确性。因此，该方法非常适合于分子成像研究，其中通常探针递送和靶点存在不被独立评估。基于这些发现，我们提出了双波长/归一化方法作为药物发现和临床前成像研究的基本方法。
Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies.