NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes as well as in the regulation of embryonic development and aging. To fluorimetrically assess the mitochondrial redox state, Dr. Chance and co-workers measured the fluorescence of NADH and oxidized flavoproteins (Fp) including flavin–adenine–dinucleotide (FAD) and demonstrated their ratio (i.e. the redox ratio) is a sensitive indicator of the mitochondrial redox states. The Chance redox scanner was built to simultaneously measure NADH and Fp in tissue at submillimeter scale in 3D using the freeze-trap protocol. This paper summarizes our recent research experience, development and new applications of the redox scanning technique in collaboration with Dr. Chance beginning in 2005. Dr. Chance initiated or actively involved in many of the projects during the last several years of his life. We advanced the redox scanning technique by measuring the nominal concentrations (in reference to the frozen solution standards) of the endogenous fluorescent analytes, i.e., [NADH] and [Fp] to quantify the redox ratios in various biological tissues. The advancement has enabled us to identify an array of the redox indices as quantitative imaging biomarkers (including [NADH], [Fp], [Fp]/([NADH]+[Fp]), [NADH]/[Fp], and their standard deviations) for studying some important biological questions on cancer and normal tissue metabolism. We found that the redox indices were associated or changed with (1) tumorigenesis (cancer versus non-cancer of human breast tissue biopsies); (2) tumor metastatic potential; (3) tumor glucose uptake; (4) tumor p53 status; (5) PI3K pathway activation in pre-malignant tissue; (6) therapeutic effects on tumors; (7) embryonic stem cell differentiation; (8) the heart under fasting. Together, our work demonstrated that the tissue redox indices obtained from the redox scanning technique may provide useful information about tissue metabolism and physiology status in normal and diseased tissues. The Chance redox scanner and other redox imaging techniques may have wide-ranging potential applications in many fields, such as cancer, diabetes, developmental process, mitochondrial diseases, neurodegenerative diseases, and aging.

中文翻译：

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用于研究组织代谢状态及其异质性的定量氧化还原成像生物标志物

NAD+/NADH 氧化还原状态与许多疾病有关，例如癌症和糖尿病，以及胚胎发育和衰老的调节。为了通过荧光法评估线粒体氧化还原状态，Chance 博士及其同事测量了 NADH 和氧化黄素蛋白 (Fp) 的荧光，包括黄素-腺嘌呤-二核苷酸 (FAD)，并证明它们的比率（即氧化还原比率）是线粒体氧化还原状态。Chance 氧化还原扫描仪旨在使用冷冻阱协议以 3D 亚毫米级同时测量组织中的 NADH 和 Fp。本文总结了我们从 2005 年开始与 Chance 博士合作的氧化还原扫描技术的最新研究经验、发展和新应用。在他生命的最后几年里，Chance 发起或积极参与了许多项目。我们通过测量内源性荧光分析物（即 [NADH] 和 [Fp]）的标称浓度（参考冷冻溶液标准）来改进氧化还原扫描技术，以量化各种生物组织中的氧化还原比率。这一进步使我们能够将一系列氧化还原指数识别为定量成像生物标志物（包括 [NADH]、[Fp]、[Fp]/([NADH]+[Fp])、[NADH]/[Fp] 和它们的标准偏差）用于研究有关癌症和正常组织代谢的一些重要生物学问题。我们发现氧化还原指数与（1）肿瘤发生相关或改变（人类乳腺组织活检的癌症与非癌症）；(2) 肿瘤转移潜能；(3) 肿瘤葡萄糖摄取；(4)肿瘤p53状态；(5)癌前组织中PI3K通路的激活；(6)对肿瘤的治疗作用；(7)胚胎干细胞分化；(8)心下禁食。总之，我们的工作表明，从氧化还原扫描技术获得的组织氧化还原指数可以提供有关正常和患病组织中组织代谢和生理状态的有用信息。Chance 氧化还原扫描仪和其他氧化还原成像技术可能在癌症、糖尿病、发育过程、线粒体疾病、神经退行性疾病和衰老等许多领域具有广泛的潜在应用。我们的工作表明，从氧化还原扫描技术获得的组织氧化还原指数可以提供有关正常和患病组织中组织代谢和生理状态的有用信息。Chance 氧化还原扫描仪和其他氧化还原成像技术可能在癌症、糖尿病、发育过程、线粒体疾病、神经退行性疾病和衰老等许多领域具有广泛的潜在应用。我们的工作表明，从氧化还原扫描技术获得的组织氧化还原指数可以提供有关正常和患病组织中组织代谢和生理状态的有用信息。Chance 氧化还原扫描仪和其他氧化还原成像技术可能在癌症、糖尿病、发育过程、线粒体疾病、神经退行性疾病和衰老等许多领域具有广泛的潜在应用。