Age-dependent changes of cerebral copper metabolism in Atp7b knockout mouse model of Wilson's disease by [Cu]CuCl-PET/CT.

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 ([C]CuCl) 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 [C]CuCl in Atp7b knockout mice, PET quantitative analysis revealed low Cu radioactivity in the brains of Atp7b knockout mice at 7th weeks of age, compared with Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [C]CuCl as a tracer. Furthermore, age-dependent increase of Cu 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 [C]CuCl-PET/CT study of Atp7b knockout mice with orally administered [Cu]CuCl as a tracer. The findings of this study support clinical use of [Cu]CuCl-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.