title: Increased oxidative stress is related to disease severity in the ALS motor cortex: A PET study.
abstract: OBJECTIVE
  To investigate cerebral oxidative stress based on an over-reductive state caused by mitochondrial dysfunction and its relationship to disease severity in patients with amyotrophic lateral sclerosis (ALS) using PET with [(62)Cu]diacetyl-bis(N(4)-methylthiosemicarbazone) ((62)Cu-ATSM).
  
  
  METHODS
  Twelve patients with ALS and 9 age-matched healthy controls underwent a 20-minute dynamic brain PET scan after (62)Cu-ATSM injection. The standardized uptake value (SUV) images obtained from the last 10 minutes of frames were normalized by the global mean (nSUV). Regional (62)Cu-ATSM retention in the nSUV images was compared between groups using statistical parametric mapping (SPM) and region of interest (ROI) analysis. Secondary analyses evaluated the correlations between regional nSUVs and the clinical characteristics of the participants.
  
  
  RESULTS
  In SPM mapping, patients with ALS showed a significantly greater accumulation of (62)Cu-ATSM compared to controls in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. ROI analysis also revealed significantly greater nSUVs in patients than controls in these regions. Increases in nSUV for these regions were associated with decreases in the revised ALS Functional Rating Scale score, suggesting a good correlation with the severity of ALS. In controls, age was correlated with nSUV for the bilateral cortices around the central sulcus, although this correlation was not observed in patients with ALS.
  
  
  CONCLUSIONS
  (62)Cu-ATSM PET imaging demonstrated increased oxidative stress based on an over-reductive state, primarily in the motor cortex, in patients with ALS. The magnitude of oxidative stress correlated well with clinical severity, indicating that it may be associated with neurodegenerative changes in ALS.
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsujikawa
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsunaga
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamamura
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Hamano
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.affiliation: From the Second Department of Internal Medicine, Faculty of Medical Sciences (M.I., A.M., O.Y., T.H., Y.N.), and Biomedical Imaging Research Center (H.O., T.T., T.M., Y.K., M.Y.), University of Fukui; and Faculty of Nursing and Social Welfare Sciences (M.Y.), Fukui Prefectural University, Japan. myoneda@fpu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoneda
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D009942:Organometallic Compounds; D018384:Oxidative Stress; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index; D013882:Thiosemicarbazones
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)