11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy

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.

Skeletal muscle and childhood cancer: Where are we now and where we go from here

“…PET with L-[methyl-11C] methionine can be used to assess both basal and responsive muscle protein synthesis rates, [50][51][52] and more recently has been validated as a less-invasive alternative to the traditional L-[ring 13 C 6 ] phenylalanine infusion with serial muscle biopsy in adults. 53 However, the use of PET to evaluate muscle protein synthesis has not been validated in children.…”

Unique advantages of dynamic l-[11C]methionine PET/CT for assessing the rate of skeletal muscle protein synthesis: A pilot trial in young men

“…The use of [ 11 C]Met PET/CT is a minimally invasive, clinically-applicable method of evaluating MPS and has been developed through animal experiments [ 8 , 9 ] and clinical studies [ 10 , 11 ] since the late 1990s. More recently, Arentson-Lantz et al demonstrated that MPS upregulation after whey protein ingestion in the elderly can be assessed using [ 11 C]Met PET/CT, similarly to the conventional method of MPS measurement using biopsy-based l -[ring- 13 C 6 ]-phenylalanine kinetics [ 12 ].…”

“…Due to the nature of muscle biopsy, the clinical target for evaluating MPS is limited mainly to large surface muscles such as the quadriceps femoris [ 12 ]. It is especially difficult to evaluate the hamstrings, which are in a deeper area, using biopsy.…”

“…It is especially difficult to evaluate the hamstrings, which are in a deeper area, using biopsy. By contrast, PET/CT enables MPS to be evaluated in the whole thigh region, including in the deeper layers [ 10 – 12 ]. Preclinical animal experiments have shown that not only the basal MPS but also increased MPS following stimuli such as exercise or nutrition varies depending on the properties of the skeletal muscles, such as the proportion of slow-twitch or fast-twitch muscles [ 13 – 16 ].…”

“…Further to the study by Arentson-Lantz et al [ 12 ], we used [ 11 C]Met PET/CT in this pilot study to investigate changes in MPS in the entire middle-thigh region of young men, following their ingestion of milk protein, which is generally composed of 20% whey and 80% casein. Furthermore, we analyzed the quadriceps and hamstrings separately to determine whether there was a difference in MPS between these muscle groups.…”