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Fangyu Peng - One of the best experts on this subject based on the ideXlab platform.

  • Advances in development of 64CuCl2 radiotracer for diagnostic imaging of Copper Metabolism disorders with PET
    Chinese Journal of Nuclear Medicine and Molecular Imaging, 2019
    Co-Authors: Fangyu Peng
    Abstract:

    Development of new radiopharmaceuticals is crucial for the advance of nuclear medicine and molecular imaging. In recent years, significant progress has been made in the development of radiopharmaceuticals based on radioactive metal nuclides such as 64Cu. Copper is a transition metal element necessary for human physiology. Disorders of Copper Metabolism not only cause hereditary Wilson disease and Menkes disease, but also play an important role in the development of malignant tumors. In addition to radiolabeling for probes, 64Cu can be used for PET diagnostic imaging of Copper Metabolism disorders. 64CuCl2 is a useful radiotracer that can be used to track the dynamic flow of Copper ions in human body Copper Metabolism by PET imaging. In recent years, many preclinical and clinical studies of 64CuCl2 radiotracer have achieved good results, and have attracted a lot of attention in the field of nuclear medicine and molecular imaging. In this article, the progress in the development of 64CuCl2 as a radiotracer for PET diagnostic imaging of hereditary Copper Metabolism disorders and Copper hypermetabolic tumors is reviewed, and further research studies and potential clinical application of 64CuCl2 PET/CT imaging is prospected. Key words: Copper radioisotopes; Positron-emission tomography; Copper; Metabolic diseases; Trends

  • Age-dependent changes of cerebral Copper Metabolism in Atp7b−/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT
    Metabolic Brain Disease, 2017
    Co-Authors: Yin Xi, Otto Muzik, Juan M. Pascual, Fangyu Peng
    Abstract:

    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 a mutation of the 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 was to explore the feasibility and use of Copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependent changes of cerebral Copper Metabolism in WD using an Atp7b−/− knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our 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 weeks of age, compared with 64Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (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 the 13th to 21th weeks of age, based on 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 clinical use of [64Cu]CuCl2-PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral Copper Metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

  • molecular imaging and therapy targeting Copper Metabolism in hepatocellular carcinoma
    World Journal of Gastroenterology, 2016
    Co-Authors: Jason W Wachsmann, Fangyu Peng
    Abstract:

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that Copper plays a role in cell proliferation and angiogenesis. Increased accumulation of Copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered Copper Metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive Copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using Copper-64 chloride as a tracer, suggesting that Copper Metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological Copper uptake. In addition to Copper modulation therapy with Copper chelators, short-interference RNA specific for human Copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased Copper uptake mediated by hCtr1. Furthermore, altered Copper Metabolism is a promising target for radionuclide therapy of HCC using therapeutic Copper radionuclides. Copper Metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

  • imaging Copper Metabolism imbalance in atp7b knockout mouse model of wilson s disease with pet ct and orally administered 64cucl2
    Molecular Imaging and Biology, 2012
    Co-Authors: Fangyu Peng, Svetlana Lutsenko, Otto Muzik
    Abstract:

    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 (64CuCl2) as a tracer.

  • positron emission tomography of Copper Metabolism in the atp7b knock out mouse model of wilson s disease
    Molecular Imaging and Biology, 2012
    Co-Authors: Fangyu Peng, Svetlana Lutsenko, Otto Muzik
    Abstract:

    Purpose This study aims to determine feasibility and utility of Copper-64(II) chloride (64CuCl2) as a tracer for positron emission tomography (PET) of Copper Metabolism imbalance in human Wilson’s disease (WD).

Otto Muzik - One of the best experts on this subject based on the ideXlab platform.

Diego Martinelli - One of the best experts on this subject based on the ideXlab platform.

  • ap1s1 defect causing mednik syndrome a new adaptinopathy associated with defective Copper Metabolism
    Annals of the New York Academy of Sciences, 2014
    Co-Authors: Diego Martinelli, Carlo Dionisivici
    Abstract:

    : MEDNIK (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia) syndrome has been recently described as a new disorder of Copper Metabolism. This multisystem disease combines clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver Copper overload is treatable using zinc acetate therapy. MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the σ1A subunit of adaptor protein complex 1, and directs intracellular trafficking of Copper pumps ATP7A and ATP7B. Adaptor protein complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. A growing number of diseases have been associated with mutations in genes coding for adaptor protein complexes subunits and we propose for them the term adaptinopathies, as a new organic category of disorders of intracellular trafficking, which offers the opportunity to dissect the mechanisms involved in the crosstalk between the Golgi apparatus and the other organelles.

  • mednik syndrome a novel defect of Copper Metabolism treatable by zinc acetate therapy
    Brain, 2013
    Co-Authors: Diego Martinelli, Lorena Travaglini, Christian A Drouin, Irene Ceballospicot, Teresa Rizza, Enrico Bertini, Rosalba Carrozzo, Stefania Petrini, Pascale De Lonlay, Maya El Hachem
    Abstract:

    MEDNIK syndrome—acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia—is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans -Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of Copper Metabolism with hypocupremia, hypoceruloplasminemia and liver Copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver Copper and bile-acid overload. We evaluated Copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular Copper Metabolism and subcellular localization and function of Copper pump ATP7A were investigated in patient fibroblasts. Copper Metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal Copper incorporation and retention, reduced expression of Copper-dependent enzymes cytochrome- c -oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular Copper machinery mediated by Copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver Copper overload is treatable by zinc acetate therapy, and can now be listed as a Copper Metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of Copper pumps. * Abbreviation : MEDNIK : mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia

  • MEDNIK syndrome: a novel defect of Copper Metabolism treatable by zinc acetate therapy.
    Brain : a journal of neurology, 2013
    Co-Authors: Diego Martinelli, Lorena Travaglini, Christian A Drouin, Teresa Rizza, Enrico Bertini, Rosalba Carrozzo, Stefania Petrini, Pascale De Lonlay, Irene Ceballos-picot, Maya El Hachem
    Abstract:

    MEDNIK syndrome-acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia-is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans-Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of Copper Metabolism with hypocupremia, hypoceruloplasminemia and liver Copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver Copper and bile-acid overload. We evaluated Copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular Copper Metabolism and subcellular localization and function of Copper pump ATP7A were investigated in patient fibroblasts. Copper Metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal Copper incorporation and retention, reduced expression of Copper-dependent enzymes cytochrome-c-oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular Copper machinery mediated by Copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver Copper overload is treatable by zinc acetate therapy, and can now be listed as a Copper Metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of Copper pumps.

Svetlana Lutsenko - One of the best experts on this subject based on the ideXlab platform.

Maya El Hachem - One of the best experts on this subject based on the ideXlab platform.

  • mednik syndrome a novel defect of Copper Metabolism treatable by zinc acetate therapy
    Brain, 2013
    Co-Authors: Diego Martinelli, Lorena Travaglini, Christian A Drouin, Irene Ceballospicot, Teresa Rizza, Enrico Bertini, Rosalba Carrozzo, Stefania Petrini, Pascale De Lonlay, Maya El Hachem
    Abstract:

    MEDNIK syndrome—acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia—is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans -Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of Copper Metabolism with hypocupremia, hypoceruloplasminemia and liver Copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver Copper and bile-acid overload. We evaluated Copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular Copper Metabolism and subcellular localization and function of Copper pump ATP7A were investigated in patient fibroblasts. Copper Metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal Copper incorporation and retention, reduced expression of Copper-dependent enzymes cytochrome- c -oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular Copper machinery mediated by Copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver Copper overload is treatable by zinc acetate therapy, and can now be listed as a Copper Metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of Copper pumps. * Abbreviation : MEDNIK : mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia

  • MEDNIK syndrome: a novel defect of Copper Metabolism treatable by zinc acetate therapy.
    Brain : a journal of neurology, 2013
    Co-Authors: Diego Martinelli, Lorena Travaglini, Christian A Drouin, Teresa Rizza, Enrico Bertini, Rosalba Carrozzo, Stefania Petrini, Pascale De Lonlay, Irene Ceballos-picot, Maya El Hachem
    Abstract:

    MEDNIK syndrome-acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia-is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans-Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of Copper Metabolism with hypocupremia, hypoceruloplasminemia and liver Copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver Copper and bile-acid overload. We evaluated Copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular Copper Metabolism and subcellular localization and function of Copper pump ATP7A were investigated in patient fibroblasts. Copper Metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal Copper incorporation and retention, reduced expression of Copper-dependent enzymes cytochrome-c-oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular Copper machinery mediated by Copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver Copper overload is treatable by zinc acetate therapy, and can now be listed as a Copper Metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of Copper pumps.