Quantification of Changes in Skeletal Muscle Amino Acid Kinetics in Adult Humans in Response to Exercise via Positron-emission Tomography with L-[methyl-11C] methionine

Abstract

Dynamic positron emission tomography (PET) imaging of with L-[methyl-11 C]methionine (11C-MET) was developed in the late 1990's to non-invasively estimate skeletal muscle protein synthesis, but no studies have shown that the measurements respond to resistance exercise, which stimulates protein synthesis in humans. Ten healthy women aged 25-75 years underwent a 14-hour fast, followed by unilateral knee extension and flexion exercise and consumption of an 8-ounce serving of fruit juice. Five subjects underwent dynamic 11C-MET PET imaging of the mid-thigh 2-3 hours after exercise and five were imaged 1 hour after exercise. Images were processed to obtain the Patlak slope K i , which describes the fractional extraction rate of 11C-MET into skeletal muscle protein. Additionally, the images were processed with a three-compartment kinetic model to determine rate constants for 11C-MET transport between muscle tissue, protein and plasma. All subjects showed excellent mid-thigh uptake of 11C-MET. Subjects imaged 2-3 hours after exercise showed no unilateral enhancement. However, subjects imaged one hour post-exercise showed an enhancement of 11C-MET uptake in the exercised leg compared to the control leg, corresponding to K i elevations between 3.8% -31.1%. From the three-compartment analysis, the increased uptake corresponded primarily to an increased rate constant for extraction of 11C-MET from plasma to skeletal muscle tissue. Finally, older subjects tended to have smaller values of K i than the younger subjects. In summary, 11C-MET kinetics is responsive to a unilateral exercise stimulus, and this technique may prove useful to study skeletal muscle amino acid kinetics in response to exercise, aging and other conditions.