Imaging phenotypes in copper metabolism disease in mice

小鼠铜代谢疾病的影像表型

• 批准号: 7230282
• 负责人: Kathryn Ann Morton
• 金额: $ 18.15万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230282
• 关键词: Address; Affect; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Appearance; Basic Science; Binding; Biochemistry; Biodistribution; Biological Availability; Biopsy; Breeding; Ceruloplasmin; Clinic; Clinical; Clinical Research; Comprehensive Health Care; Control Animal; Copper; Count; Cuprozinc Superoxide Dismutase; Data; Development; Diagnosis; Disease; Disease Progression; Dissection; Educational workshop; Feasibility Studies; Functional disorder; Future; Genes; Genetic; Goals; Half-Life; Hematology; Hepatic; Homeostasis; Hour; Human; Image; Imaging Device; Individual; Industry; Inherited; Invasive; Ions; Iron; Isotopes; Kinetics; Knowledge; Life; Longitudinal Studies; Malignant Neoplasms; Menkes Kinky Hair Syndrome; Metabolism; Metals; Methods; Modeling; Molecular Abnormality; Mus; Mutation; Numbers; Nutritional; Organ; Patient Care; Patients; Phenotype; Physiology; Positron; Positron-Emission Tomography; Proteins; Purpose; Radioactive; Radiopharmaceuticals; Rate; Rattus; Research; Research Methodology; Research Personnel; Resources; Rodent Model; Route; Scientist; Spinal; Syndrome; System; Technology; Therapeutic; Time; Tissues; Transferrin; Transgenic Mice; Universities; Utah; Washington; absorption; base; body system; cancer therapy; day; design; editorial; gene therapy; genetic analysis; human disease; interest; molecular imaging; mouse model; mutant; novel; pre-clinical; symposium; therapy design; tool; trafficking; uptake; yeast protein

DESCRIPTION (provided by applicant): Copper metabolism disease (CMD) is represents a spectrum of abnormalities characterized by abnormal content, distribution or metabolism of copper in the body. These diseases include nutritional, acquired and genetic abnormalities in one or more of the regulatory steps required in copper homeostasis. These diseases can have serious consequences to the patient, affecting multiple organ systems and resulting in abnormalities in the bioavailability of other essential metal ions. The diseases are often difficult to diagnose, and are of great interest to scientists who strive to understand basic metallophysiology and pathophysiology. Copper-related therapies may be of interest in the treatment of cancer and other diseases. Studies of CMD have traditionally been limited by the lack of relevant animal models for many of the diseases, the availability of Cu isotopes for research, and methods to non-invasively, non-destructively and longitudinally assess the kinetics and distribution of copper in the body. Recent developments have provided opportunities to circumvent these limitations, including the characterization of many novel rodent models of specific CMD's, the technology of microPET (positron emission tomography), the availability of Cu-64, a positron emitter with a half life permissive of longitudinal studies from hours to days (provided by an NIH-supported National Research Resource by Washington University, St. Louis). MicroPET imaging, and ex-vivo biodistribution studies of 64-Cu in rodent models of genetically acquired CMD will be utilized to establish whether distinct imaging phenotypes define well-characterized inherited rodent models of CMD's, and whether phenotypic rescue of specific disorders by novel therapies normalizes the imaging phenotype. These pilot data will be used to justify RO1 applications to explore non-invasive methods to diagnose CMD's, to understand the underlying pathophysiology that contributes to these disorders, and to assess the efficacy of novel copper- based therapies. The establishment of the imaging phenotypes of CMD in animal models is also critical to enable non-invasive, non-destructive and longitudinal methods for evaluating novel gene therapies designed to reverse or ameliorate the consequences of lacking or abnormal gene products that contribute to CMD. These imaging tools will be of use to numerous local and regional investigators addressing normal and abnormal copper metabolism, its resultant diseases and treatment of patients with these disorders.

描述（由申请人提供）：铜代谢疾病（CMD）是一系列以体内铜含量、分布或代谢异常为特征的异常。这些疾病包括铜稳态所需的一个或多个调节步骤中的营养、获得性和遗传异常。这些疾病可能对患者造成严重后果，影响多个器官系统，并导致其他必需金属离子的生物利用度异常。这些疾病通常很难诊断，并且对努力了解基本金属生理学和病理生理学的科学家非常感兴趣。铜相关疗法可能对癌症和其他疾病的治疗有意义。CMD的研究传统上受到缺乏许多疾病的相关动物模型，Cu同位素研究的可用性以及非侵入性，非破坏性和纵向评估体内铜的动力学和分布的方法的限制。最近的发展提供了规避这些限制的机会，包括许多特定CMD的新型啮齿动物模型的表征，microPET（正电子发射断层扫描）技术，Cu-64的可用性，Cu-64是一种正电子发射体，其半衰期允许从数小时到数天的纵向研究（由圣路易斯华盛顿大学NIH支持的国家研究资源提供）。MicroPET成像和64-Cu在遗传获得性CMD的啮齿动物模型中的离体生物分布研究将用于确定不同的成像表型是否定义了良好表征的遗传性CMD啮齿动物模型，以及通过新疗法对特定疾病的表型拯救是否使成像表型正常化。这些试验数据将用于证明R 01应用于探索诊断CMD的非侵入性方法、了解导致这些疾病的潜在病理生理学以及评估新型铜基疗法的功效。在动物模型中建立CMD的成像表型对于实现用于评估新基因疗法的非侵入性、非破坏性和纵向方法也是至关重要的，所述新基因疗法被设计为逆转或改善导致CMD的基因产物缺乏或异常的后果。这些成像工具将用于许多地方和区域研究人员解决正常和异常铜代谢，其导致的疾病和治疗这些疾病的患者。