title: Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET.
abstract: Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG).
  
  
  
  Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method.
  
  
  
  The means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively).
  
  
  
  Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsujikawa
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Asahi
authors.affiliation: Department of Otolaryngology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Myungmi
authors.initials: M
authors.lastname: Oh
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Otolaryngology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Narita
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Otolaryngology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
mesh_terms: D000368:Aged; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008297:Male; D009942:Organometallic Compounds; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D013882:Thiosemicarbazones
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D005462:Fluorine Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18