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This study aims to determine feasibility and utility of copper-64(II) chloride ((64)CuCl(2)) as a tracer for positron emission tomography (PET) of copper metabolism imbalance in human Wilson's disease (WD).
Atp7b (-/-) mice, a mouse model of human WD, were injected with (64)CuCl(2) intravenously and subjected to PET scanning using a hybrid PET-CT (computerized tomography) scanner, with the wild-type C57BL mice as a normal control. Quantitative PET analysis was performed to determine biodistribution of (64)Cu radioactivity and radiation dosimetry estimates of (64)Cu were calculated for PET of copper metabolism in humans.
Dynamic PET analysis revealed increased accumulation and markedly reduced clearance of (64)Cu from the liver of the Atp7b (-/-) mice, compared to hepatic uptake and clearance of (64)Cu in the wild-type C57BL mice. Kinetics of copper clearance and retention was also altered for kidneys, heart, and lungs in the Atp7b (-/-) mice. Based on biodistribution of (64)Cu in wild-type C57BL mice, radiation dosimetry estimates of (64)Cu in normal human subjects were obtained, showing an effective dose (ED) of 32.2 μ (micro)Sv/MBq (weighted dose over 22 organs) and the small intestine as the critical organ for radiation dose (61 μGy/MBq for males and 69 μGy/MBq for females). Radiation dosimetry estimates for the patients with WD, based on biodistribution of (64)Cu in the Atp7b (-/-) mice, showed a similar ED of 32.8 μ (micro)Sv/MBq (p = 0.53), with the liver as the critical organ for radiation dose (120 μSv/MBq for male and 161 μSv/MBq for female).
Quantitative PET analysis demonstrates abnormal copper metabolism in the mouse model of WD with improved time-resolution. Human radiation dosimetry estimates obtained in this preclinical study encourage direct radiation dosimetry of (64)CuCl(2) in human subjects. The results suggest feasibility of utilizing (64)CuCl(2) as a tracer for noninvasive assessment of copper metabolism in WD with PET.
Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8542, USA, Fangyu.Peng@UTSouthwestern.edu.
This article was published in the following journal.
Name: Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging
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 mutatio...
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