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首页> 外文期刊>Neoplasia: an international journal for oncology research >In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment
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In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment

机译：在肿瘤异质性的体内自体荧光成像响应治疗

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Subpopulations of cells that escape anti-cancer treatment can cause relapse in cancer patients. Therefore, measurements of cellular-level tumor heterogeneity could enable improved anti-cancer treatment regimens. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. The optical redox ratio (fluorescence intensity of NAD(P)H divided by FAD) reflects global cellular metabolism. The fluorescence lifetime (amount of time a fluorophore is in the excited state) is sensitive to microenvironment, particularly protein-binding. High-resolution imaging of the optical redox ratio and fluorescence lifetimes of NAD(P)H and FAD (optical metabolic imaging) enables single-cell analyses. In this study, mice with FaDu tumors were treated with the antibody therapy cetuximab or the chemotherapy cisplatin and imaged in vivo two days after treatment. Results indicate that fluorescence lifetimes of NAD(P)H and FAD are sensitive to early response (two days post-treatment, P?&?.05), compared with decreases in tumor size (nine days post-treatment, P?&?.05). Frequency histogram analysis of individual optical metabolic imaging parameters identifies subpopulations of cells, and a new heterogeneity index enables quantitative comparisons of cellular heterogeneity across treatment groups for individual variables. Additionally, a dimensionality reduction technique (viSNE) enables holistic visualization of multivariate optical measures of cellular heterogeneity. These analyses indicate increased heterogeneity in the cetuximab and cisplatin treatment groups compared with the control group. Overall, the combination of optical metabolic imaging and cellular-level analyses provide novel, quantitative insights into tumor heterogeneity.
机译：逃避抗癌治疗的细胞的亚群可导致癌症患者的复发。因此，细胞级肿瘤异质性的测量可以改善抗癌治疗方案。癌症表现出改变的细胞代谢，这会影响代谢辅因子NAD（P）H和FAD的自发荧光。光学氧化还原比（NAD荧光强度（P）H除以FAD）反映了全局细胞代谢。荧光寿命（荧光团在激发态中的时间量）对微环境，特别是蛋白质结合敏感。 NAD（P）H和FAD（光学代谢成像）的光学氧化还原比和荧光寿命的高分辨率成像使单细胞分析能够。在这项研究中，用抗体治疗香嘧啶或化疗顺铂治疗小鼠，并在治疗后两天在体内成像。结果表明，NAD（P）H和FAD的荧光寿命对早期反应（治疗后两天，p≤05），与肿瘤大小的降低相比（治疗后九天，P≤1。 ;？05）。各种光学代谢成像参数的频率直方图分析鉴定细胞的亚群，新的异质性指数能够在各个变量的治疗组中进行定量比较细胞异质性。另外，维度降低技术（Visne）能够实现多变量的细胞异质性的多变量光学测量的整体可视化。这些分析表明，与对照组相比，西妥昔单抗和顺铂治疗组中的异质性增加。总的来说，光学代谢成像和细胞水平分析的组合提供了新的，定量洞察肿瘤异质性。

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