title: MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES.
abstract: 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 × 10μm3) 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 10μm.Ex vivoimaging andin vivoimaging 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.
authors.affiliation: Department of Radiology, School of Medicine, University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6069, USA ; The Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lin Z
authors.initials: LZ
authors.lastname: Li
authors.affiliation: Department of Radiology, School of Medicine, University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6069, USA.
authors.forename: He N
authors.initials: HN
authors.lastname: Xu
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Ranji
authors.affiliation: Johnson Research Foundation, Department of Biochemistry and Molecular Biophysics, School of Medicine, University of Pennsylvania, 250 Anatomy Chemistry Building, Philadelphia, PA 19104, USA.
authors.forename: Shoko
authors.initials: S
authors.lastname: Nioka
authors.affiliation: Johnson Research Foundation, Department of Biochemistry and Molecular Biophysics, School of Medicine, University of Pennsylvania, 250 Anatomy Chemistry Building, Philadelphia, PA 19104, USA.
authors.forename: Britton
authors.initials: B
authors.lastname: Chance
keywords: FAD; NADH; Redox ratio; calibration; flavin adenine dinucleotide; flavoprotein; reduced nicotinamide adenine dinucleotide