title: Age-dependent changes of cerebral copper metabolism in Atp7b-/-knockout mouse model of Wilson's disease by [64Cu]CuCl2-PET/CT.
abstract: Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b-/-knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [64C]CuCl2in Atp7b-/-knockout mice, PET quantitative analysis revealed low64Cu radioactivity in the brains of Atp7b-/-knockout mice at 7th weeks of age, compared with64Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [64C]CuCl2as a tracer. Furthermore, age-dependent increase of64Cu radioactivity was detected in the brains of Atp7b-/-knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b-/-knockout mice with orally administered [64Cu]CuCl2as a tracer. The findings of this study support clinical use of [64Cu]CuCl2-PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9140, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9140, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pascual
authors.affiliation: Carman & Ann Adams Department of Pediatrics, Wayne State University, Detroit, MI, USA.|Department of Radiology, School of Medicine, Wayne State University, Detroit, MI, USA.
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9140, USA. Fangyu.Peng@UTSouthwestern.edu.|Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Fangyu.Peng@UTSouthwestern.edu.
authors.forename: Fangyu
authors.identifier: http://orcid.org/0000-0002-3142-3845
authors.initials: F
authors.lastname: Peng
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes / Q000378:metabolism*; D000073840:Copper-Transporting ATPases / Q000172:deficiency*; D004195:Disease Models, Animal; D005260:Female; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods
chemical_list: D003301:Copper Radioisotopes; C000615411:Copper-64; D003300:Copper; C000612461:Atp7b protein, mouse; D000073840:Copper-Transporting ATPases; C029892:cupric chloride
keywords: Atp7b gene; Copper metabolism; Copper-64 chloride; Neurodegeneration; Positron emission tomography; Wilson’s disease