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Mol Imaging Biol. 2012 Feb;14(1):70-8. doi: 10.1007/s11307-011-0476-4.

Positron emission tomography of copper metabolism in the Atp7b-/- knock-out mouse model of Wilson's disease.

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  • 1Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8542, USA. Fangyu.Peng@UTSouthwestern.edu

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.

PMID:
21327972
[PubMed - indexed for MEDLINE]
PMCID:
PMC3157550
Free PMC Article
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