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

Fangyu Peng, Svetlana Lutsenko, Iankai Sun, Otto Muzik

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Abstract

Purpose: This study aims to determine feasibility and utility of copper-64(II) chloride ( 64CuCl 2) 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 64CuCl 2intravenously 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 64CuCl 2 in human subjects. The results suggest feasibility of utilizing 64CuCl 2 as a tracer for noninvasive assessment of copper metabolism in WD with PET.

Original languageEnglish (US)
Pages (from-to)70-78
Number of pages9
JournalMolecular Imaging and Biology
Volume14
Issue number1
DOIs
Publication statusPublished - Feb 2012

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Keywords

  • ATP7B copper transporter
  • Copper metabolism
  • Copper-64 (II) chloride
  • Positron emission tomography
  • Radiation dosimetry
  • Wilson's disease

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

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