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Positron Emission Tomography of Copper Metabolism in the Atp7b (-/-) Knock-out Mouse Model of Wilson's Disease.

06:00 EST 18th February 2011 | BioPortfolio

Summary of "Positron Emission Tomography of Copper Metabolism in the Atp7b (-/-) Knock-out Mouse Model of Wilson's Disease."


PURPOSE:
This study aims to determine feasibility and utility of copper-64(II) chloride ((64)CuCl(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 (64)CuCl(2) 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 (64)Cu radioactivity and radiation dosimetry estimates of (64)Cu were calculated for PET of copper metabolism in humans.
RESULTS:
Dynamic PET analysis revealed increased accumulation and markedly reduced clearance of (64)Cu from the liver of the Atp7b (-/-) mice, compared to hepatic uptake and clearance of (64)Cu 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 (64)Cu in wild-type C57BL mice, radiation dosimetry estimates of (64)Cu 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 (64)Cu 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 (64)CuCl(2) in human subjects. The results suggest feasibility of utilizing (64)CuCl(2) as a tracer for noninvasive assessment of copper metabolism in WD with PET.

Affiliation

Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8542, USA, Fangyu.Peng@UTSouthwestern.edu.

Journal Details

This article was published in the following journal.

Name: Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging
ISSN: 1860-2002
Pages:

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Medical and Biotech [MESH] Definitions

An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.

A method of computed tomography that uses radionuclides which emit a single photon of a given energy. The camera is rotated 180 or 360 degrees around the patient to capture images at multiple positions along the arc. The computer is then used to reconstruct the transaxial, sagittal, and coronal images from the 3-dimensional distribution of radionuclides in the organ. The advantages of SPECT are that it can be used to observe biochemical and physiological processes as well as size and volume of the organ. The disadvantage is that, unlike positron-emission tomography where the positron-electron annihilation results in the emission of 2 photons at 180 degrees from each other, SPECT requires physical collimation to line up the photons, which results in the loss of many available photons and hence degrades the image.

The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162)

The creation of a visual display of the inside of the entire body of a human or animal for the purposes of diagnostic evaluation. This is most commonly achieved by using MAGNETIC RESONANCE IMAGING; or POSITRON EMISSION TOMOGRAPHY.

A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 3.6.3.4), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years.

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