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Molecular Imaging and Biology

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01-02-2012 | Research Article

Positron Emission Tomography of Copper Metabolism in the Atp7b ^−/− Knock-out Mouse Model of Wilson’s Disease

Authors: Fangyu Peng, Svetlana Lutsenko, Xiankai Sun, Otto Muzik

Published in: Molecular Imaging and Biology | Issue 1/2012

Abstract

Purpose

This study aims to determine feasibility and utility of copper-64(II) chloride (⁶⁴CuCl₂) as a tracer for positron emission tomography (PET) of copper metabolism imbalance in human Wilson’s disease (WD).

Procedures

Atp7b ^−/− mice, a mouse model of human WD, were injected with ⁶⁴CuCl₂ 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 ⁶⁴Cu radioactivity and radiation dosimetry estimates of ⁶⁴Cu were calculated for PET of copper metabolism in humans.

Results

Dynamic PET analysis revealed increased accumulation and markedly reduced clearance of ⁶⁴Cu from the liver of the Atp7b ^−/− mice, compared to hepatic uptake and clearance of ⁶⁴Cu 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 ⁶⁴Cu in wild-type C57BL mice, radiation dosimetry estimates of ⁶⁴Cu 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 ⁶⁴Cu 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).

Conclusions

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 ⁶⁴CuCl₂ in human subjects. The results suggest feasibility of utilizing ⁶⁴CuCl₂ as a tracer for noninvasive assessment of copper metabolism in WD with PET.

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Title: Positron Emission Tomography of Copper Metabolism in the Atp7b −/− Knock-out Mouse Model of Wilson’s Disease
Authors: Fangyu Peng
Svetlana Lutsenko
Xiankai Sun
Otto Muzik
Publication date: 01-02-2012
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 1/2012
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-011-0476-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Positron Emission Tomography of Copper Metabolism in the Atp7b ^−/− Knock-out Mouse Model of Wilson’s Disease

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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