Quantification, Variability, and Reproducibility of Basal Skeletal Muscle Glucose Uptake in Healthy Humans Using ¹⁸F-FDG PET/CT

Abstract

The quantification and variability of skeletal muscle glucose utilization (SMGU) in healthy subjects under basal (low insulin) conditions are poorly known. This information is essential early in clinical drug development to effectively interrogate novel pharmacologic interventions that modulate glucose uptake. The aim of this study was to determine test-retest characteristics and variability of SMGU within and between healthy subjects under basal conditions. Furthermore, different kinetic modeling strategies were evaluated to find the bestfitting model to assess SMGU studied by 18 F-FDG. Methods: Six healthy male volunteers underwent 2 dynamic 18 F-FDG PET/CT scans with an interval of 24 h. Subjects were admitted to the clinical unit to minimize variability in daily activities and food intake and restrict physical activity. 18 F-FDG PET/CT scans of gluteal and quadriceps muscle area were obtained with arterial input. Regions of interest were drawn over the muscle area to obtain time-activity curves and standardized uptake values (SUVs) between 60 and 90 min. Spectral analysis of the data and kinetic modeling was performed using 2-tissue-irreversible (2T3K), 2-tissue-reversible, and 3-tissue-sequential-irreversible (3T5KS) models. Reproducibility was assessed by intraclass correlation coefficients (ICCs) and within-subject coefficient of variation (WSCV). Results: SUVs in gluteal and quadriceps areas were 0.56 ± 0.09 and 0.64 ± 0.07. ICCs (with 90% confidence intervals in parentheses) were 0.88 (0.64-0.96) and 0.96 (0.82-0.99), respectively, for gluteal and quadriceps muscles, and WSCV for gluteal and quadriceps muscles was 2.2% and 3.6%, respectively. The rate of glucose uptake into muscle was 0.0016 ± 0.0004 mL/mL⋅min, with an ICC of 0.94 (0.93-0.95) and WSCV of 6.6% for the 3T5KS model, whereas an ICC of 0.98 (0.92-1.00) and WSCV of 2.8% was obtained for the 2T3K model. 3T5KS demonstrated the best fit to the measured experimental points. Conclusion: Minimal variability in skeletal muscle glucose uptake was observed under basal conditions in healthy subjects. SUV measurements and rate of glucose uptake values were reproducible, with an average WSCV of less than 5%. Compared with SUV, the 3-tissue model adds information about kinetics between blood, intra-and intercellular compartments, and phosphorylation that may highlight the exact mechanisms of metabolic changes after pharmacologic intervention.

Regional Variation in Skeletal Muscle and Adipose Tissue FDG Uptake Using PET/CT and Their Relation to BMI

“…In combination with VAT, we identified two skeletal muscle groups (PM, GM) whose activity accounted for 64% of the variance in BMI (Table 2). In accordance with our findings, the GM was recently shown to be a highly reproducible location for measuring basal skeletal muscle FDG uptake with high intraclass correlation (0.88) and low within-subject variation (2.2%) (35). It is unclear why only the PM and GM correlated significantly with BMI, but we speculate that these sites are the most reliable measurements of basal muscle activity due to their relatively large volume and the lack of muscle activity at rest.…”

“…Our the small sample size and lack of random selection of subjects could potentially lead to a selection bias and type II error in our analysis. Recent data, however, suggest that studies with as little as 6–8 subjects could detect significant changes in skeletal muscle SUV between groups (35). Additionally, our study only enrolled men between the ages of 30 and 50 years of age.…”

Diagnostic yield of 18F-FDG PET/CT imaging and urinary CXCL9/creatinine levels in kidney allograft subclinical rejection

“…The mean standardized uptake value (mSUV) of kidney cortex was measured and averaged from 4 volumes of interest (VOI) distributed in the upper (n = 2) and lower (n = 2) poles. The mSUV of kidney was normalized to the mSUV of psoas muscle (VOI of 20 mL) considered as reference tissue in order to obtain the mean SUV ratio (mSUVR) . Neither the liver nor the mediastinum was within the field of the graft‐centered scan, which hampers the use of liver or blood pool as references.…”

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition

“…www.nature.com/scientificreports www.nature.com/scientificreports/ It is well known that glucose and [ 18 F]FDG uptake rate is influenced by muscle fiber composition and muscle activity level 27 . Gluteal muscles were recently shown to be a highly reproducible location for measuring basal skeletal muscle [ 18 F]FDG uptake rate with high intraclass correlation coefficient (ICC = 0.88) and low within-subject variation (2.2%) 28 . The increased uptake rate in these muscles can be explained by the fact that the gluteus maximus, one of the muscles that compose this group, is the biggest and strongest muscle of the whole body; moreover, their principal and most powerful function is to cause the body to regain the erect position after stopping and they are the chief muscles that work against gravity when a subject goes up stairs.…”