PET/CT of skeletal muscle amino acid kinetics

骨骼肌氨基酸动力学的 PET/CT

• 批准号: 8531863
• 负责人: THOMAS F LANG
• 金额: $ 13.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-17 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531863
• 关键词: Acetates; Adipose tissue; Affect; Aging; Amino Acids; Anatomic Sites; Anatomy; Beds; Biochemical; Biological Markers; Biopsy; Biopsy Specimen; Cachexia; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Conduct Clinical Trials; Cyclotrons; Data; Diffusion; Disease; Elderly; Exercise; Fasting; Female; Functional Imaging; Functional disorder; Future; Goals; Gold; HIV therapy; Health Care Costs; Health system; Image; Infiltration; Infusion procedures; Intervention; Kinetics; Light; Limb structure; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Medical Research; Metabolism; Methods; Microscopic; Modeling; Molecular; Molecular Genetics; Muscle; Muscle Proteins; Muscle function; Needle biopsy procedure; Non-Insulin-Dependent Diabetes Mellitus; Nursing Homes; Nutritional; Obesity; Oxygen Consumption; Pain; Phenylalanine; Population; Positron-Emission Tomography; Production; Property; Protease Inhibitor; Protein Biosynthesis; Proteins; Protocols documentation; Public Health; Quality of life; Radiopharmaceuticals; Renal carcinoma; Research; Resolution; Role; Skeletal Muscle; Stable Isotope Labeling; Stimulus; Techniques; Technology; Thigh structure; Three-Dimensional Imaging; Time; Tissues; Ursidae Family; Work; X-Ray Computed Tomography; age related; base; design; disability; feeding; fluorodeoxyglucose positron emission tomography; glucose metabolism; imaging modality; improved; in vivo; intervention effect; metabolic abnormality assessment; methionine methyl ester; muscle aging; muscle form; research study; response; sarcopenia; stable isotope; uptake; wasting

DESCRIPTION (provided by applicant): Muscle-wasting among the elderly and other affected populations causes loss of independence and is an important factor in the rising public health costs of nursing home confinement. It is associated with primary age-related muscle loss as well as the secondary effects of conditions such as Type 2 Diabetes, protease inhibitor therapy for HIV, chronic kidney disease and cancer cachexia. Clinical research studies investigating the pathophysiology and treatment of muscle loss often utilize CT and MRI imaging to depict disease and treatment-related changes in the size and adiposity of skeletal muscle. However, the only available clinical functional imaging of skeletal muscle involves assessment of glucose metabolism and there are no available measures of amino acid metabolism. Such information is critical for understanding both muscle loss and the anabolic effects of interventions, and must now be obtained by carrying out a separate skeletal muscle biopsy, which is painful, time-consuming and logistically complicated. The goal of our study is to clinically develop a technique to assess skeletal muscle amino acid metabolism using clinical dynamic positron emission tomography/computed tomography (PET/CT) imaging of 11C-L-Methyl-Methionine (11C-MET) in conjunction with three-compartment analysis. PET/CT is a technology that is now undergoing rapid clinical diffusion in the US and is widely found at academic medical research centers, with over a thousand PET/CT units installed in the US, and with close to 100 centers containing an onsite cyclotron for radiopharmaceutical production. The goals of our study involve gaining preliminary data in elderly subjects on the response of 11C-MET PET/CT imaging to nutritional stimulus of skeletal muscle protein synthesis and verifying that responses against the skeletal muscle biopsy, the gold standard technique. As a result of this work, we will have the information required to apply this method to clinical research studies, opening up important fundamental questions about the role of altered amino acid metabolism in muscle-wasting-related disability, improving our ability to characterize interventions, and in correlating morphologic with functional changes in skeletal muscle.

描述（由申请人提供）：老年人和其他受影响人群的肌肉萎缩会导致独立性的丧失，并且是养老院监禁公共卫生成本上升的一个重要因素。它与年龄相关的原发性肌肉损失以及 2 型糖尿病、艾滋病毒蛋白酶抑制剂治疗、慢性肾病和癌症恶病质等疾病的继发影响有关。调查肌肉损失的病理生理学和治疗的临床研究通常利用 CT 和 MRI 成像来描述疾病和治疗相关的骨骼肌大小和脂肪变化。然而，唯一可用的骨骼肌临床功能成像涉及葡萄糖代谢的评估，并且没有可用的氨基酸代谢测量方法。这些信息对于了解肌肉损失和干预措施的合成代谢效应至关重要，现在必须通过进行单独的骨骼肌活检来获得，这是痛苦、耗时且后勤复杂的。我们研究的目标是临床开发一种技术，利用 11C-L-甲基甲硫氨酸 (11C-MET) 的临床动态正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像并结合三室分析来评估骨骼肌氨基酸代谢。 PET/CT 是一项目前正在美国快速临床推广的技术，广泛应用于学术医学研究中心，美国安装了 1000 多台 PET/CT 设备，近 100 个中心配备了用于放射性药物生产的现场回旋加速器。我们研究的目标包括获得老年受试者关于 11C-MET PET/CT 成像对骨骼肌蛋白质合成营养刺激反应的初步数据，并验证针对骨骼肌活检（黄金标准技术）的反应。这项工作的结果是，我们将获得将该方法应用于临床研究所需的信息，提出有关氨基酸代谢改变在肌肉萎缩相关残疾中的作用的重要基本问题，提高我们描述干预措施的能力，以及将骨骼肌形态与功能变化相关联的能力。