MEASUREMENT OF MUSCLE PROTEIN-SYNTHESIS BY POSITRON EMISSION TOMOGRAPHY WITH L-[METHYL-C-11]METHIONINE

Positron emission tomography (PET) with L-[methyl-C-11]methionine was explored as an in vivo, noninvasive, quantitative method for measuring the protein synthesis rate (PSR) in paraspinal and hind limb muscles of anesthetized dogs. Approximately 25 mCi (1 Ci = 37 GBq) of L-[methy l-C-11]methionine was injected intravenously, and serial images and ar terial blood samples were acquired over 90 min. Data analysis was perf ormed by fitting tissue- and metabolite-corrected arterial blood time- activity curves to a three-compartment model and assuming insignifican t transamination and transmethylation in this tissue. PSR was calculat ed from fitted parameter values and plasma methionine concentrations. PSRs measured by PET were compared with arterio-venous (A-V) differenc e measurements across the hind limb during primed constant infusion (5 -6 h) of L-[1-C-13, methyl-H-2(3)]methionine. Results of PET measureme nts demonstrated similar PSRs for paraspinal and hind limb muscles: 0. 172 +/- 0.062 vs. 0.208 +/- 0.048 nmol(-1). min(-1).(g of muscle)(-1) (P = not significant). PSR determined by the stable isotope technique was 0.27 +/- 0.050 nmol(-1). min(-1).(g of leg tissue)(-1) (P < 0.07 f rom PET) and indicated that the contribution of transmethylation to to tal hind limb methionine utilization was approximate to 10%. High leve ls of L-[methyl-C-11] methionine utilization by bone marrow were obser ved. We conclude that muscle PSR can be measured in vivo by PET and th at this approach offers promise for application in human metabolic stu dies.