MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES.
MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES.
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DOI：
10.1142/s1793545809000735
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发表时间：
2009-10
影响因子：
2.5
通讯作者：
Chance B
中科院分区：
文献类型：
--
作者：
Li LZ;Xu HN;Ranji M;Nioka S;Chance B
线粒体氧化还原状态提供了有关包括癌症在内的各种疾病表型的组织中与能量相关的生物过程和信号事件的重要信息。 Chance实验室大约30年前开发的氧化还原扫描方法，基于NADH（还原型烟酰胺腺嘌呤二核苷酸）和Fp（氧化黄素蛋白，包括黄素腺嘌呤二核苷酸，即FAD）的荧光，可以对组织中的线粒体氧化还原状态进行3D高分辨率（约50×50×10μm3）成像。在这篇综述中，我们阐述了其基本原理、最新技术发展以及在小动物模型癌症诊断和治疗研究中的生物医学应用。最近开发的使用参考标准的氧化还原成像校准程序可以量化标称 NADH 和 Fp 浓度以及基于浓度的氧化还原比，例如组织中的 Fp/(Fp+NADH) 和 NADH/(Fp+NADH)。这种校准有助于比较在不同时间和/或使用不同仪器设置针对不同代谢状态获得的氧化还原成像结果。使用 CCD 探测器的氧化还原成像仪已开发出来，可以更快地获取 3D 图像，面内分辨率高达 10 μm。组织线粒体氧化还原状态的离体成像和体内成像已通过 CCD 成像仪得到证实。组织氧化还原成像在小动物癌症模型中的应用包括神经胶质瘤和 myc 诱导的小鼠乳腺肿瘤的代谢成像、预测人类黑色素瘤和乳腺癌小鼠异种移植物的转移潜力、区分癌前组织和正常组织以及监测肿瘤治疗对光动力疗法的反应。还讨论了氧化还原成像未来可能的发展方向。
Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including cancer. The redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D high-resolution (~ 50 × 50 × 10 μm3) imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and Fp (oxidized flavoproteins including flavin adenine dinucleotide, i.e., FAD). In this review, we illustrate its basic principles, recent technical developments, and biomedical applications to cancer diagnostic and therapeutic studies in small animal models. Recently developed calibration procedures for the redox imaging using reference standards allow quantification of nominal NADH and Fp concentrations, and the concentration-based redox ratios, e.g., Fp/(Fp+NADH) and NADH/(Fp+NADH) in tissues. This calibration facilitates the comparison of redox imaging results acquired for different metabolic states at different times and/or with different instrumental settings. A redox imager using a CCD detector has been developed to acquire 3D images faster and with a higher in-plane resolution down to 10 μm. Ex vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD imager. Applications of tissue redox imaging in small animal cancer models include metabolic imaging of glioma and myc-induced mouse mammary tumors, predicting the metastatic potentials of human melanoma and breast cancer mouse xenografts, differentiating precancerous and normal tissues, and monitoring the tumor treatment response to photodynamic therapy. Possible future directions for the development of redox imaging are also discussed.