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MITOCHONDRIAL REDOX IMAgINg FOR CANCER DIAgNOSTIC AND THERAPEUTIC STUDIES

Journal of Innovative Optical Health Sciences 2009年第4期2卷 325-341页

作者： LIN Z.LI HE N.XU MAHSA RANJI SHOKO NIOKA BRITTON CHANCE Department of Radiology School of Medicine University of PennsylvaniaB6 Blockley Hall423 Guardian Drive PhiladelphiaPA 19104-6069USA The Institute for Translational Medicine and Therapeutics School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Biophotonics Laboratory Department of Electrical Engineering and Computer Science University of Wisconsin-Milwaukee MilwaukeeWI 53211USA Johnson Research foundation Department of Biochemistry and Molecular Biophysics School of Medicine University of Pennsylvania 250 Anatomy Chemistry BuildingPhiladelphiaPA 19104USA

Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including *** redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D highresolution(∼50×50×10µm^(3))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 *** 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 *** 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 10µ*** vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD *** 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 *** future directions for the development of redox imaging are also discussed.

关键词： Redox ratio reduced nicotinamide adenine dinucleotide NADH flavoprotein flavin adenine dinucleotide FAD calibration

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QUANTITATIVE REDOX SCANNINg OF TISSUE SAMPLES USINg A CALIBRATION PROCEDURE

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 375-385页

作者： HE N.XU BAOHUA WU SHOKO NIOKA BRITTON CHANCE LIN Z.LI Molecular Imaging Laboratory Department of Radiology University of PennsylvaniaPhiladelphia PA 19104USA Johnson Research foundation Department of Biochemistry and Biophysics University of Pennsylvania PA 19104USA

The fluorescence properties of reduced nicotinamide adenine dinucleotide(NADH)and oxidizedflavoproteins(Fp)including flavin adenine dinucleotide(FAD)in the respiratory chain are sensitive indicators of intracellular metabolic states and have been applied to the studies of mitochondrial function with energy-linked *** redox scanner,a three-dimensional(3D)low temperature imager previously developed by Chance et al.,measures the in vivo metabolicproperties of tissue samples by acquiring fluorescence images of NADH and *** redox ratios,***/(Fp+NADH)and NADH/(Fp+NADH),provided a sensitive index of the mitochondrialredox state and were determined based on relative signal intensity *** we report thefurther development of the redox scanning technique by using a calibration method to quantifythe nominal concentration of the fluorophores in *** redox scanner exhibited very goodlinear response in the range of NADH concentration between 165–1318µM and Fp between90–720µM using snap-frozen solution *** samples such as human tumor mousexenografts and various mouse organs were redox-scanned together with adjacent NADH and Fpstandards of known concentration at liquid nitrogen *** nominal NADH and Fpconcentrations as well as the redox ratios in the tissue samples were quantified by normalizing the tissue NADH and Fp fluorescence signal to that of the snap-frozen solution *** calibration procedure allows comparing redox images obtained at different time,independent of instrument *** quantitative multi-slice redox images revealed heterogeneity inmitochondrial redox state in the tissues.

关键词： NADH flavoprotein redox ratio mitochondria tissue heterogeneity

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Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies

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Cancer Biology & Medicine 2014年第1期11卷 1-19页

作者： Liem Minh Phan Sai-Ching Jim Yeung Mong-Hong Lee Department of Molecular and Cellular Oncology Department of general Internal Medicine Ambulatory Treatment and Emergency Care Department of Endocrine Neoplasia and Hormonal Disorders The University of Texas MD Anderson Cancer Center

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warburg's discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.

关键词：物质代谢癌症患者重编程抗肿瘤治疗疗法抗癌瞄准肿瘤细胞

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应用强斯氧化还原扫描仪探测小鼠体内组织代谢状态空间分布

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中国医疗设备 2013年第6期28卷 1-6页

作者：孟丽丽孙楠楠李琳宾夕法尼亚大学佩雷尔曼医学院放射学系分子成像实验室美国宾州费城19104 宾夕法尼亚大学佩雷尔曼医学院生物化学和生物物理系强森研究基金会布立顿.强斯氧化还原成像实验室美国宾州费城19104

氧化还原状态能为癌症等多种疾病提供组织内与能量相关的生物过程和信号活动等方面的重要信息。强斯氧化还原扫描仪根据还原型烟酰胺腺嘌呤二核苷酸(NADH)和氧化型黄素蛋白(Fp,包括黄素腺嘌呤二核苷酸即FAD)的荧光信号建立组织内线粒体... 详细信息

氧化还原状态能为癌症等多种疾病提供组织内与能量相关的生物过程和信号活动等方面的重要信息。强斯氧化还原扫描仪根据还原型烟酰胺腺嘌呤二核苷酸(NADH)和氧化型黄素蛋白(Fp,包括黄素腺嘌呤二核苷酸即FAD)的荧光信号建立组织内线粒体氧化还原三维高清图像。本文阐述了强斯氧化还原扫描仪的基本原理和方法,分析了对正常和肿瘤组织的扫描结果,显示组织内氧化还原态空间分布的异质性,并对强斯氧化还原扫描仪在医学中的应用潜力进行初步的探讨。

关键词：强斯氧化还原扫描仪氧化黄素蛋白黄素腺嘌呤二核苷酸烟酰胺腺嘌呤二核苷酸氧化还原态氧化还原比组织异质性组织代谢

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This research was supported by ***6 Integrated Project“Molecular Imaging”LSHg-CT-2003-503259 and ***7 Collaborative Project“FMT-XCT”.*** support from the Marie Curie Program EST-MolecImag Early Stage Training MEST-CT-2004-007643.

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 365-374页

作者： MAHSA RANJI SHOKO NIOKA HE N.XU BAOHUA WU LIN Z.LI DWIgHT L.JAggARD BRITTON CHANCE Biophotonics Laboratory Department of Electrical Engineering and Computer Science University of Wisconsin-Milwaukee MilwaukeeWI 53211USA Department of Electrical and Systems Engineering University of Pennsylvania PhiladelphiaPA 19104USA Department of Biochemistry and Biophysics University of Pennsylvania PhiladelphiaPA 19104USA Department of Radiology University of Pennsylvania PhiladelphiaPA 19104USA

We have imaged mitochondrial oxidation-reduction states by taking a ratio of mitochondrial fluorophores:NADH(reduced nicotinamide adenine dinucleotide)to Fp(oxidized flavoprotein).Although NADH has been investigated for tissue metabolic state in cancer and in oxygen deprived tissues,it alone is not an adequate measure of mitochondrial metabolic state since the NADH signal is altered by dependence on the number of mitochondria and by blood *** redox ratio,NADH/(Fp+NADH),gives a more accurate measure of steady-state tissue metabolism since it is less dependent on mitochondrial number and it compensates effectively for hemodynamic *** ratio provides important diagnostic information in living *** this study,the emitted fluorescence of mouse colon in situ is passed through an emission filter wheel and imaged on a CCD *** ratio images of the healthy and hypoxic mouse intestines clearly showed significant ***,the corrected redox ratio indicated an increase from an average value of 0.51±0.10 in the healthy state to 0.92±0.03 in dead tissue due to severe ischemia(N=5).We show that the CCD imaging system is capable of displaying the metabolic differences in normal and ischemic tissues as well as quantifying the redox ratio in vivo as a marker of these changes.

关键词： Optical diagnosis NADH flavoprotein in vivo ischemia fluorescence.

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