Molecular Imaging and Biology

, Volume 14, Issue 1, pp 70–78

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

  • Fangyu Peng
  • Svetlana Lutsenko
  • Xiankai Sun
  • Otto Muzik
Research Article

DOI: 10.1007/s11307-011-0476-4

Cite this article as:
Peng, F., Lutsenko, S., Sun, X. et al. Mol Imaging Biol (2012) 14: 70. doi:10.1007/s11307-011-0476-4

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.

Key words

Copper metabolismWilson’s diseaseATP7B copper transporterPositron emission tomographyCopper-64 (II) chlorideRadiation dosimetry

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Fangyu Peng
    • 1
    • 2
    • 3
  • Svetlana Lutsenko
    • 4
  • Xiankai Sun
    • 1
    • 2
  • Otto Muzik
    • 5
    • 6
  1. 1.Department of RadiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Advanced Imaging Research CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Harold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  4. 4.Department of PhysiologyJohns Hopkins UniversityBaltimoreUSA
  5. 5.Carman & Ann Adams Department of PediatricsSchool of Medicine, Wayne State UniversityDetroitUSA
  6. 6.Department of RadiologySchool of Medicine, Wayne State UniversityDetroitUSA