PET/CT of skeletal muscle amino acid kinetics

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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.