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

doi:10.1007/s11307-011-0476-4

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

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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 language	English (US)
Pages (from-to)	70-78
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1007/s11307-011-0476-4
State	Published - Feb 1 2012

Keywords

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

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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@article{3bb0b9d38f9d4ade9ea890c0e99c4e54,

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

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.",

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

author = "Fangyu Peng and Svetlana Lutsenko and Iankai Sun and Otto Muzik",

year = "2012",

month = feb,

day = "1",

doi = "10.1007/s11307-011-0476-4",

language = "English (US)",

volume = "14",

pages = "70--78",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "1",

}

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

PY - 2012/2/1

Y1 - 2012/2/1

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

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