Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT.
Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT.
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DOI：
10.1038/srep27017
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Evans CL
中科院分区：
文献类型：
--
作者：
Jung Y;Klein OJ;Wang H;Evans CL
三维体外肿瘤模型是研究卵巢癌等恶性肿瘤生长和治疗反应的非常有用的工具。然而，现有的生存力和治疗评估测定法在应用于这些大型、复杂和异质的培养系统时面临缺点。光学相干断层扫描（OCT）是一种非侵入性、无标记的光学成像技术，可以随着时间的推移以亚细胞分辨率和毫米级的光学穿透深度可视化活细胞和组织。在这里，我们表明，OCT能够进行高内容，纵向测定的三维培养治疗反应。我们证明了OCT的使用和能力的动态监测的个人和联合治疗方案在体外，包括化疗药物和光动力疗法（PDT）卵巢癌。在小肿瘤球状体培养物中，根据标准活/死活力/细胞毒性试验对OCT进行了验证，显示出与现有标准的良好相关性。重要的是，OCT被证明能够评估3D球体治疗反应，即使传统的活力测定失败。OCT 3D活力成像显示PDT和标准治疗化疗卡铂之间的协同作用随时间推移而发展。我们相信OCT体外药物筛选的有效性和准确性将大大有助于癌症治疗和治疗评价领域。
Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.