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

Authors

    • Department of RadiologyUniversity of Texas Southwestern Medical Center
    • Advanced Imaging Research CenterUniversity of Texas Southwestern Medical Center
    • Harold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical Center
  • Svetlana Lutsenko
    • Department of PhysiologyJohns Hopkins University
  • Xiankai Sun
    • Department of RadiologyUniversity of Texas Southwestern Medical Center
    • Advanced Imaging Research CenterUniversity of Texas Southwestern Medical Center
  • Otto Muzik
    • Carman & Ann Adams Department of PediatricsSchool of Medicine, Wayne State University
    • Department of RadiologySchool of Medicine, Wayne State University
Research Article

DOI: 10.1007/s11307-011-0532-0

Cite this article as:
Peng, F., Lutsenko, S., Sun, X. et al. Mol Imaging Biol (2012) 14: 600. doi:10.1007/s11307-011-0532-0

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 metabolismWilson’s diseasePositron emission tomographyPET-CTCopper (II)-64 chlorideRadiation dosimetry

Copyright information

© World Molecular Imaging Society 2011