Assessment of Traumatic Brain Injury by Increased 64Cu Uptake on 64CuCl2 PET/CT

Peng, Fangyu; Muzik, Otto; Gatson, Joshua W.; Kernie, Steven G.

doi:10.2967/jnumed.115.154575

Cited by 18 publications

(13 citation statements)

References 37 publications

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“…Our findings are in line with previous studies that applied [ 64 Cu]CuCl 2 as a tracer for investigation of cerebral copper metabolism in aging mice with autoradiography [25], study of changes of cerebral copper metabolism in a mouse model of Menkes disease [26], as well as diagnostic imaging of traumatic brain injury [13]. To determine whether 64 Cu radioactivity measured by PET/CT is correlated with the concentration of endogenous copper ions in mouse tissues, copper concentration of mouse tissues was determined by ICP-MS and correlated with 64 Cu biodistribution in Balb/c mice on [ 64 Cu]CuCl 2 -PET/CT imaging (Fig 3).…”

Section: Discussionsupporting

confidence: 91%

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Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

Xie

Pascual

et al. 2017

Metab Brain Dis

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Copper is a nutritional metal required for brain development and function. Wilson’s disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by mutation of ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study is to explore feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependence changes of cerebral copper metabolism in WD using an Atp7b−/− knockout mouse model of WD and a positron emission tomography/computed tomography (PET/CT) scanner. Continuing from recent study of biodistribution and radiation dosimetry of [64C]CuCl2 in Atp7b−/− knockout mice, PET quantitative analysis revealed low 64Cu radioactivity in the brains of Atp7b−/− knockout mice at 7th week of age, compared with the 64Cu radioactivity in the brains of age and gender-matched wild type C57BL/6 mice, at 24 hour (h) post intravenous injection of [64C]CuCl2 as a tracer. Furthermore, age-dependent increase of 64Cu radioactivity was detected in the brains of Atp7b−/− knockout mice from 13th to 21th week of age, using the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b−/− knockout mice with orally administered [64Cu]CuCl2 as a tracer. The findings of this study support the use of [64Cu]CuCl2-PET/CT as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

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Section: Discussionsupporting

confidence: 91%

“…[ 64 Cu]CuCl 2 -PET/CT imaging of Balb/c mice was performed using a method described previously [7–9, 13]. Briefly, Balb/c mice were anesthetized by 3% isoflurane in 100% oxygen (3 L/min) at room temperature, using an isoflurane vaporizer (Summit Anesthesia Solutions, Salt Lake City, UT).…”

Section: Methodsmentioning

confidence: 99%

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

Xie

Pascual

et al. 2017

Metab Brain Dis

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“…A meta-analysis [ 144 ] and the following investigations [ 105 , 145 ] revealed a lower total Cu in AD, while the level of labile Cu is higher in most of the brain areas affected by this disease [ 105 ]. Alzheimer’s brain tissues and the cortexes of transgenic animals with severe brain damage showed the high Cu 2+ ions-binding capacity [ 105 , 146 ]. Additionally, the APPsw/0 mouse model study reported parenchymal Aβ plaques, but no damage to neurons has been observed ( Table 1 ) [ 147 , 148 ].…”

Section: Copper Ion Implication In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

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Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.

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“…Copper is required for brain development and physiology although the role of copper in brain aging remains to be elucidated. Radionuclide 64 Cu is a positron emitting copper isotope and 64 CuCl 2 was used as a radiotracer for noninvasive assessment of disturbance of cerebral copper fluxes in traumatic brain injury [ 28 ] and age-dependent changes of copper fluxes in Atp7b -/- knockout mouse model of Wilson’s disease [ 25 ]. Applying 64 CuCl 2 -PET/CT imaging in a mouse model of brain aging, we present data that show age-related differences in brain copper fluxes across the life span.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Copper Fluxes in Brain Aging: A Longitudinal Study in Rodent Using 64CuCl2-PET/CT

Peng¹,

Xie

Muzik

2018

Aging and disease

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Brain aging is associated with changes of various metabolic pathways. Copper is required for brain development and function, but little is known about changes in copper metabolism during brain aging. The objective of this study was to investigate alteration of copper fluxes in the aging mouse brain with positron emission tomography/computed tomography using 64CuCl2 as a radiotracer (64CuCl2-PET/CT). A longitudinal study was conducted in C57BL/6 mice (n = 5) to measure age-dependent brain and whole-body changes of 64Cu radioactivity using PET/CT after oral administration of 64CuCl2 as a radiotracer. Cerebral 64Cu uptake at 13 months of age (0.17 ± 0.05 %ID/g) was higher than the cerebral 64Cu uptake at 5 months of age (0.11 ± 0.06 %ID/g, p < 0.001), followed by decrease to (0.14 ± 0.04 %ID/g, p = 0.02) at 26 months of age. In contrast, cerebral 18F-FDG uptake was highest at 5 months of age (7.8 ± 1.2 %ID/g) and decreased to similar values at 12 (5.2 ± 1.1 %ID/g, p < 0.001) and 22 (5.6 ± 1.1 %ID/g, p < 0.001) months of age. The findings demonstrated alteration of copper fluxes associated with brain aging and the time course of brain changes in copper fluxes differed from changes in brain glucose metabolism across time, suggesting independent underlying physiological processes. Hence, age-dependent changes of cerebral copper fluxes might represent a novel metabolic biomarker for assessment of human brain aging process with PET/CT using 64CuCl2 as a radiotracer.

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Assessment of Traumatic Brain Injury by Increased ⁶⁴Cu Uptake on ⁶⁴CuCl₂ PET/CT

Cited by 18 publications

References 37 publications

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Alteration of Copper Fluxes in Brain Aging: A Longitudinal Study in Rodent Using 64CuCl2-PET/CT

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