Optical imaging of tumor hypoxia dynamics
Optical imaging of tumor hypoxia dynamics
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DOI：
10.1117/1.3523363
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发表时间：
2010-11-01
影响因子：
3.5
通讯作者：
Dewhirst, Mark W.
中科院分区：
文献类型：
--
作者：
Palmer, Gregory M.;Fontanella, Andrew N.;Dewhirst, Mark W.
肿瘤微环境和缺氧的影响在决定肿瘤进展、治疗反应和治疗抵抗中起着重要作用。肿瘤微环境是高度异质性的，具有显著的肿瘤内和肿瘤间变异性，这对开发有效的癌症治疗提出了重大挑战。了解肿瘤微环境作用的关键是能够动态量化血管和组织中的氧气水平，以阐明氧气供应和消耗在空间和时间上的作用。为此，我们描述了使用高光谱成像来表征血红蛋白吸收，以量化血红蛋白含量和氧饱和度，以及双发射荧光/磷光硼纳米颗粒，作为组织氧张力的比率指标。将这些技术应用于窗腔肿瘤模型说明了血红蛋白饱和度波动在驱动组织氧合变化中的作用，两者显着相关（r = 0.77）。最后，低氧诱导因子-1 （HIF-1）的绿色荧光蛋白报告基因提供了肿瘤缺氧应激的终点，在该技术的体内演示中，它被用来证明肿瘤缺氧动力学和HIF-1活性之间的显著关联。(C) 2010国际光学工程学会。(DOI: 10.1117/1.3523363)
The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique. (C) 2010 The International Society for Optical Engineering. [DOI: 10.1117/1.3523363]