The purpose of the present study is to investigate exercise-related changes in skeletal muscle of rodents and humans with PET and [11C]acetate. A pre-clinical and a clinical protocol were implemented, the veterinary experiment involving the application of kinetic analysis to investigate the metabolism of skeletal rat muscle and its comparison to more conventional quantitation approaches. Osteoarthritis represents a chronic disease that causes significant burdens to patients and there is now increasing evidence in literature as well as from clinical practice, that muscle weakness probably plays a contributory role in the onset and progression of osteoarthritis. PET allows the study of tissue metabolism in vivo in a non-invasive way, enabling to quantitatively characterise physiologic processes. To the best of our knowledge, just a few studies in literature investigated the metabolic fate of acetate in the skeletal muscle at rest and after exercise using PET monitoring and kinetic analysis.