PET/CT of skeletal muscle amino acid kinetics

骨骼肌氨基酸动力学的 PET/CT

基本信息

批准号：
8368700
负责人：
THOMAS F LANG
金额：
$ 17.55万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-17 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8368700
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

项目摘要

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. PUBLIC HEALTH RELEVANCE: By clinically developing PET/CT imaging of 11C-L-Methyl Methionine we will bring to bear a new biomarker of skeletal muscle function in aging, disease and therapy, opening new research questions in studies of sarcopenia pathophysiology and response to interventions.

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，并且是疗养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，使用 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，结合三种技术来评估骨骼肌氨基酸代谢。 -房室分析。 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，在美国安装了 1000 多台 PET/CT 设备，并且有近 100 个中心配备了现场回旋加速器，可用于诊断和治疗。放射性药物生产。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（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，并将骨骼肌的形态与功能变化联系起来。公共健康相关性：通过临床开发 11C-L-甲基蛋氨酸 PET/CT 成像，我们将带来衰老、疾病和治疗中骨骼肌功能的新生物标志物，在肌少症病理生理学和干预反应研究中提出新的研究问题。