Masamichi Ikawa1, Hidehiko Okazawa1, Tetsuya Tsujikawa1, Akiko Matsunaga1, Osamu Yamamura1, Tetsuya Mori1, Tadanori Hamano1, Yasushi Kiyono1, Yasunari Nakamoto1, Makoto Yoneda2. 1. 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. 2. 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.
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.
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: Stefanie M A Willekens; Donatienne Van Weehaeghe; Philip Van Damme; Koen Van Laere Journal: Eur J Nucl Med Mol Imaging Date: 2016-12-08 Impact factor: 9.236
Authors: Adam Southon; Kathryn Szostak; Karla M Acevedo; Krista A Dent; Irene Volitakis; Abdel A Belaidi; Kevin J Barnham; Peter J Crouch; Scott Ayton; Paul S Donnelly; Ashley I Bush Journal: Br J Pharmacol Date: 2020-01-14 Impact factor: 8.739
Authors: Jared R Williams; Emiliano Trias; Pamela R Beilby; Nathan I Lopez; Edwin M Labut; C Samuel Bradford; Blaine R Roberts; Erin J McAllum; Peter J Crouch; Timothy W Rhoads; Cliff Pereira; Marjatta Son; Jeffrey L Elliott; Maria Clara Franco; Alvaro G Estévez; Luis Barbeito; Joseph S Beckman Journal: Neurobiol Dis Date: 2016-01-27 Impact factor: 5.996