Redox ratio of mitochondria as an indicator for the response of photodynamic therapy.
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.
Zhang
Zhihong
Z
Huazhong University of Science and Technology, Key Laboratory of Biomedical Photonics, Ministry of Education, Wuhan, Hubei 430074, P.R. China.
Blessington
Dana
D
Li
Hui
H
Busch
Theresa M
TM
Glickson
Jerry
J
Luo
Qingming
Q
Chance
Britton
B
Zheng
Gang
G
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
D014408:Biomarkers, Tumor; D005420:Flavoproteins; D017319:Photosensitizing Agents; C482914:pyropheophorbide 2-deoxyglucosamide; D009243:NAD; D003847:Deoxyglucose