PET/CT of skeletal muscle amino acid kinetics

描述（由申请人提供）：老年人和其他受影响人群的肌肉萎缩导致丧失独立性，是养老院坐月子公共卫生费用上升的一个重要因素。它与原发性与年龄相关的肌肉损失以及2型糖尿病、HIV蛋白酶抑制剂治疗、慢性肾病和癌症恶病质等疾病的继发性影响有关。研究肌肉损失的病理生理学和治疗的临床研究经常使用CT和MRI成像来描述骨骼肌大小和脂肪的疾病和治疗相关的变化。然而，骨骼肌唯一可用的临床功能成像包括葡萄糖代谢评估，没有可用的氨基酸代谢测量。这些信息对于理解肌肉损失和干预的合成代谢影响至关重要，现在必须通过进行单独的骨骼肌活检来获得，这是痛苦的，耗时的，后勤复杂的。我们的研究目的是临床开发一种技术来评估骨骼肌氨基酸代谢使用临床动态正电子发射断层扫描/计算机断层扫描（PET/CT）成像11c - l-甲基蛋氨酸（11C-L-Methyl-Methionine, 11C-MET）结合三室分析。PET/CT是一项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，近100个中心包含用于放射性药物生产的现场回旋加速器。我们的研究目标包括在老年受试者中获得11C-MET PET/CT成像对骨骼肌蛋白质合成营养刺激的反应的初步数据，并验证骨骼肌活检（金标准技术）的反应。通过这项工作，我们将获得将该方法应用于临床研究所需的信息，揭开氨基酸代谢改变在肌肉萎缩相关残疾中的作用的重要基础问题，提高我们表征干预措施的能力，以及将骨骼肌的形态与功能变化联系起来的能力。

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.