Tracing oxidative metabolism: [¹¹C]acetate-PET with radiometabolite correction reveals early hepatic metabolic alterations in the diet-induced MAFLD model

Résumé fourni par la source

• [¹¹C]acetate-PET can be used for metabolic assessment during MAFLD. • [¹¹C]CO₂ excretion varies over time between healthy and MAFLD models. • Compartmental modeling demonstrated a clear separation of hepatic function between healthy and MAFLD groups. [¹¹C]Acetate-PET, widely applied in cardiology and oncology, offers unique potential as a non-invasive imaging method for assessing oxidative metabolism in metabolic disorders. In this study, we investigated its ability to detect early metabolic changes in the diet-induced model of metabolic dysfunction-associated fatty liver disease (MAFLD). Sprague Dawley rats were maintained on either standard diet or high-fat diet for 10 weeks before undergoing dynamic [ 11 C]acetate-PET/CT measurement. Four weeks later, radiometabolite analysis was performed in half of the animals, while the remainder underwent non-radioactive blood gas measurements. Uptake of [ 11 C]acetate at 60 minutes after administration was quantified in the kidneys, myocardium, and liver (SUV mean and SUV max ), followed by analysis of time activity curves (AUC), alongside monoexponential clearance rates (k mono ) and kinetic modeling using 1- and 2-tissue compartment models (V t ). MAFLD animals exhibited altered [¹¹C]acetate metabolism, with [ 11 C]CO 2 excretion patterns validated by non-radiative blood gas analyses. While healthy rats showed a radiometabolite peak at ∼30 min post-injection, MAFLD rats displayed an earlier maximum at 5 min and a secondary peak at 40 min, indicating a shift in longitudinal oxidative metabolism. Despite contradictions between SUVs and k mono, compartmental modeling demonstrated a clear separation of healthy from MAFLD groups, solely in hepatic volume of distribution (V t ). These results establish repurposing of [ 11 C]acetate-PET, particularly when combined with metabolite correction, as a sensitive approach for phenotyping and identifying metabolic alterations in MAFLD and also hold translational promise for understanding and monitoring of other obesity-related liver dysfunctions.

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