title: Optical redox imaging indices discriminate human breast cancer from normal tissues.
abstract: Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues ( p < 0.05 ). The redox ratio Fp/(NADH + Fp) was ? 27 % higher in the cancerous tissues ( p < 0.05 ). Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients.
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Department of Radiology, Molecular Imaging Laboratory, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104, United StatesbUniversity of Pennsylvania, Perelman School of Medicine, Department of Biochemistry and Biophysics, Johnson Research Foundation, Britton Chance Laboratory of Redox Imaging, R171 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, United States.
authors.forename: He N
authors.initials: HN
authors.lastname: Xu
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Division of Endocrine and Oncologic Surgery, Department of Surgery, West Pavilion 3rd Floor, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, United StatesdUniversity of Pennsylvania, Perelman School of Medicine, Abramson Cancer Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, United StateseUniversity of Pennsylvania, Perelman School of Medicine, Rena Rowan Breast Center, West Pavilion, 3rd Floor, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Tchou
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Department of Radiology, Molecular Imaging Laboratory, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104, United StatesbUniversity of Pennsylvania, Perelman School of Medicine, Department of Biochemistry and Biophysics, Johnson Research Foundation, Britton Chance Laboratory of Redox Imaging, R171 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Temple University, School of Medicine, Department of Clinical Sciences, Kresge Room 218, 3440 North Broad Street, Philadelphia, Pennsylvania 19140, United States.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Zhao
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Department of Radiology, Molecular Imaging Laboratory, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104, United StatesbUniversity of Pennsylvania, Perelman School of Medicine, Department of Biochemistry and Biophysics, Johnson Research Foundation, Britton Chance Laboratory of Redox Imaging, R171 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, United StatesdUniversity of Pennsylvania, Perelman School of Medicine, Abramson Cancer Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Lin Z
authors.initials: LZ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000737:chemistry; D001706:Biopsy; D001940:Breast / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000032:analysis / Q000737:chemistry; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry; D057054:Molecular Imaging / Q000379:methods*; D009243:NAD / Q000032:analysis / Q000737:chemistry; D010084:Oxidation-Reduction; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D009243:NAD; D005182:Flavin-Adenine Dinucleotide