TY - JOUR
T1 - Positron emission tomography of copper metabolism in the Atp7b -/- knock-out mouse model of Wilson's disease
AU - Peng, Fangyu
AU - Lutsenko, Svetlana
AU - Sun, Iankai
AU - Muzik, Otto
N1 - Funding Information:
Acknowledgments. The authors thank Jon Anderson and Anjali Gupta for technical support in calibration of PET-CT scanner and PET-CT scanning, and Guiyang Hao for help in tracer injection. This project was funded partially by National Institutes of Health, USA (R21EB005331-01A2 to F.P; R56DK084510 to SL) and the Department of Radiology and Harold C. Simmons Comprehensive Cancer Center, at University of Texas South-western Medical Center at Dallas, TX, USA. The production of Cu-64 at Washington University School of Medicine is supported by NCI grant R24 CA86307. The authors declare that they have no conflict of interest.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - ATP7B copper transporter
KW - Copper metabolism
KW - Copper-64 (II) chloride
KW - Positron emission tomography
KW - Radiation dosimetry
KW - Wilson's disease
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U2 - 10.1007/s11307-011-0476-4
DO - 10.1007/s11307-011-0476-4
M3 - Article
C2 - 21327972
AN - SCOPUS:84861481585
VL - 14
SP - 70
EP - 78
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
SN - 1536-1632
IS - 1
ER -