Abstract
ObjectiveThe objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe).MethodsHealthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle.ResultsPost-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min−1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015).ConclusionsDynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.
Highlights
Muscle-wasting conditions place a significant burden on the public health system and are a threat to independence and quality of life [1, 2]
In a previous study [10], we reported a high correlation (r = 0.92) between Ki and the muscle protein synthesis (MPS) rate estimated by Fishman et al [8] from kinetic analysis using a three compartment model of dynamic positron emission tomography (PET) data
The prevalence of sarcopenia and other clinical conditions are associated with muscle-wasting motivate the development of strategies to reduce or prevent disability
Summary
Muscle-wasting conditions place a significant burden on the public health system and are a threat to independence and quality of life [1, 2]. The measurement of acute localized skeletal muscle protein fractional synthesis rate (FSR) is traditionally used to quantify the response to an anabolic stimulus [3, 4]. This moderately invasive procedure includes a stable isotope infusion (e.g., L- [ring-13C6] phenylalanine (13C-Phe)), peripheral venous blood sampling, and serial needle muscle biopsies, typically from the vastus lateralis. The stable isotope, 3-pool modeling technique provides an estimate of protein synthesis and breakdown, but requires femoral venous and arterial catheterization [5] While these methodologies continue to be used successfully in a variety of clinical research environments [6, 7], they may be contraindicated for clinically vulnerable populations. A technology to rapidly and non-invasively evaluate skeletal muscle protein anabolism would have significant impact on the assessment of musclewasting and associated countermeasures in people unable to tolerate prolonged, more invasive studies
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