Abstract 10378: Metabolomic Signatures of Myocardial Glucose Uptake on FDG-PET

Abstract

Introduction: FDG-PET is critical for evaluating myocardial inflammation, but requires preparation with a ketogenic diet (KD) to suppress physiologic myocardial glucose uptake (MGU). Even in monitored settings, incomplete suppression occurs in ~20% and remains the Achilles’ heel of the KD technique. We recently found in a crossover trial (NCT04275453; KEETO-CROSS) that despite achieving robust ketosis, ketone ester (KE) drink was inferior to KD to suppress MGU. We sought to understand whether a common metabolite signature might predict myocardial glucose suppression (MGS) irrespective of technique to ensure adequate myocardial preparation. Methods: Twenty healthy participants were first randomly assigned to acute KE ingestion or KD (24/72 hour visits) with subsequent crossover. Targeted plasma metabolomic profiling of 61 metabolites was performed at these 3 visits paired with FDG-PET. The association between metabolites and MGU was assessed using mixed effects linear regression. Results: The mean age of the participants was 30±7 years (50% women and 45% non-white). The Figure shows volcano plots for the relationship between metabolites and MGU. In both arms, two C4-OH carnitine species (markers of ketone/fatty acid oxidation) were strongly and inversely associated with MGU. Both species (C4-OH isobutyrylcarnitine and C4-OH butyrylcarnitine) were predictive of MGS in all patients (c-statistic 0.83, 95% CI 0.65-1.00 and 0.81, 95% CI 0.70-0.92, respectively) and much stronger than ketone/fatty acid levels. C4-OH isobutyrylcarnitine levels were higher during 24/72 hour KD visits than KE (p=0.018 and p=0.003). Conclusions: Metabolite markers of ketone and fatty acid oxidation strongly predict MGS, have robust discriminatory value, and may be used upstream of FDG-PET to reduce false positive scans. Strategies to enhance ketone/fatty acid oxidation (rather than circulating ketone/fatty acid levels) may improve MGS.