title: Redox ratio of mitochondria as an indicator for the response of photodynamic therapy.
abstract: The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.
authors.affiliation: Huazhong University of Science and Technology, Key Laboratory of Biomedical Photonics, Ministry of Education, Wuhan, Hubei 430074, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dana
authors.initials: D
authors.lastname: Blessington
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.forename: Jerry
authors.initials: J
authors.lastname: Glickson
authors.forename: Qingming
authors.initials: Q
authors.lastname: Luo
authors.forename: Britton
authors.initials: B
authors.lastname: Chance
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005420:Flavoproteins / Q000032:analysis / Q000378:metabolism; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011379:Prognosis; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005420:Flavoproteins; D017319:Photosensitizing Agents; C482914:pyropheophorbide 2-deoxyglucosamide; D009243:NAD; D003847:Deoxyglucose