Imaging copper metabolism imbalance in Atp7b (-/-) knockout mouse model of Wilson's disease with PET-CT and orally administered 64CuCl2.
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 ((64)CuCl...
| Publicado en: | Molecular Imaging & Biology Vol. 14; no. 5; pp. 600 - 608 |
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| Autores principales: | , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Oct2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104383300&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104383300 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Oct2012 vid: 14 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104383300 104383300 NLM22170165 2011754228 10.1007/s11307-011-0532-0 NLM22170165 104383300 ppf: 600 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Imaging copper metabolism imbalance in Atp7b (-/-) knockout mouse model of Wilson's disease with PET-CT and orally administered 64CuCl2. aug: au: Peng F Lutsenko S Sun X Muzik O Peng, Fangyu Lutsenko, Svetlana Sun, Xiankai Muzik, Otto affil: Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Hines Blvd, Dallas, TX 75390-8542, USA sug: subj: Adenosine Triphosphatase Deficiency Carrier Proteins Deficiency Copper Metabolism Radioisotopes Administration and Dosage Hepatolenticular Degeneration Radiography Molecular Imaging Methods Adenosine Triphosphatase Metabolism Administration, Oral Adult Animals Carrier Proteins Metabolism Copper Administration and Dosage Copper Pharmacokinetics Radioisotopes Pharmacokinetics Models, Biological Dose-Response Relationship, Radiation Female Human Male Mice Radiometry Time Factors Adult: 19-44 years Female Male ab: 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 ((64)CuCl(2)) as a tracer.Procedures: Atp7b (-/-) KO mice (N = 5) were subjected to PET scanning using a hybrid PET-CT scanner, after oral administration of (64)CuCl(2) as a tracer. Time-dependent PET quantitative analysis was performed to assess gastrointestinal absorption and biodistribution of (64)Cu 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 (64)Cu radioactivity in live animals.Results: PET-CT analysis demonstrated higher (64)Cu radioactivity in the liver of Atp7b (-/-) knockout mice compared with that in the control C57BL WT mice (p < 0.001), following oral administration of (64)CuCl(2) as a tracer. In addition, (64)Cu 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 (64)Cu, there was no significant difference of (64)Cu radioactivity in the kidneys of the Atp7b (-/-) KO mice and the control C57BL WT mice at 24 h post-oral administration of (64)CuCl(2) (p = 0.16). There was no significant difference in low (64)Cu 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 (64)Cu radioactivity in C57BL WT mice, radiation dosimetry estimates of (64)Cu 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 (64)Cu 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 (64)Cu radioactivity in the liver of Atp7b (-/-) KO mice compared with that in the control C57BL WT mice, following oral administration of (64)CuCl(2) as a tracer. The results of this study suggest the feasibility and utility of PET-CT using orally administered (64)CuCl(2) as a tracer ((64)CuCl(2)-PET/CT) for functional imaging of copper metabolism imbalance in WD. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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