Molecular Imaging and Biology

, Volume 14, Issue 5, pp 600–607

Imaging Copper Metabolism Imbalance in Atp7b−/− Knockout Mouse Model of Wilson’s Disease with PET-CT and Orally Administered 64CuCl2

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

Abstract

Objectives

This study aims to determine the feasibility and utility of functional imaging of copper metabolism imbalance in Atp7b−/− knockout mouse model of Wilson’s disease (WD) with positron emission tomography-computed tomography (PET-CT) using orally administered copper-64 chloride (64CuCl2) as a tracer.

Procedures

Atp7b−/− KO mice (N = 5) were subjected to PET scanning using a hybrid PET-CT scanner, after oral administration of 64CuCl2 as a tracer. Time-dependent PET quantitative analysis was performed to assess gastrointestinal absorption and biodistribution of 64Cu radioactivity in the Atp7b−/− KO mice, using C57BL wild-type (WT) mice (N = 5) as a normal control. Estimates of human radiation dosimetry were calculated based on biodistribution of 64Cu radioactivity in live animals.

Results

PET-CT analysis demonstrated higher 64Cu radioactivity in the liver of Atp7b−/− knockout mice compared with that in the control C57BL WT mice (p < 0.001), following oral administration of 64CuCl2 as a tracer. In addition, 64Cu radioactivity in the lungs of the Atp7b−/− knockout mice was slightly higher than those in the control C57BL WT mice (p = 0.01). Despite initially higher renal clearance of 64Cu, there was no significant difference of 64Cu radioactivity in the kidneys of the Atp7b−/− KO mice and the control C57BL WT mice at 24 h post-oral administration of 64CuCl2 (p = 0.16). There was no significant difference in low 64Cu radioactivity in the blood, brain, heart, and muscles between the Atp7b−/− knockout mice and control C57BL WT mice (p > 0.05). Based on the biodistribution of 64Cu radioactivity in C57BL WT mice, radiation dosimetry estimates of 64Cu in normal human subjects were obtained. An effective dose (ED) of 42.4 μSv/MBq (weighted dose over 22 organs) was calculated and the lower large intestines were identified as the critical organ for radiation exposure (120 μGy/MBq for males and 135 μGy/MBq for females). Radiation dosimetry estimates for patients with WD, derived from the biodistribution of 64Cu in Atp7b−/− KO mice, showed a slightly lower ED of 37.5 μSv/MBq, with the lower large intestines as the critical organ for radiation exposure (83 μSv/MBq for male and 95 μSv/MBq for female).

Conclusions

PET-CT quantitative analysis demonstrated an increased level of 64Cu radioactivity in the liver of Atp7b−/− KO mice compared with that in the control C57BL WT mice, following oral administration of 64CuCl2 as a tracer. The results of this study suggest the feasibility and utility of PET-CT using orally administered 64CuCl2 as a tracer (64CuCl2-PET/CT) for functional imaging of copper metabolism imbalance in WD.

Key words

Copper metabolism Wilson’s disease Positron emission tomography PET-CT Copper (II)-64 chloride Radiation dosimetry 

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Copyright information

© World Molecular Imaging Society 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

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