Abstract 12657: PET Imaging of Fatty Acid Oxidation and Glucose Uptake in Heart and Skeletal Muscle of Rats: Effects of CPT-1 Inhibition
Fatty acid oxidation (FAO) is a major energy-producing process in heart (H) and skeletal muscle (SM) that has critical importance in coronary heart disease, heart failure, cardiomyopathies, obesity and diabetes. In this study, we evaluate the utility of microPET imaging with 18-[18F]fluoro-4-thia-oleate (FTO) and [18F]FDG to monitor changes in FAO and glucose uptake, respectively, in response to carnitine palmitoyltransferase I (CPT-1) inhibition by 2-(5-(4-chlorophenyl)pentyl)oxirane-2-carboxylic acid (POCA) in living rats. FTO or FDG was administered IV to fasted Sprague-Dawley rats (n=4 each group) under control conditions or 2 h after IP pretreatment with 30 mg/kg POCA. Furthermore, to understand the dependence of SM uptake of the tracers to contractions, unilateral stimulation (2.5 Hz) of the vastus lateralis muscle was performed 30 m prior and continued for 30 m following tracer injection. FTO uptake at 2 h p.i. by heart (standardized uptake value (SUV)=5.4±0.7) was 85% reduced in POCA treated rats, while FDG uptake at 1 h p.i. (SUV=0.93±0.39) was 64-fold enhanced by POCA. FTO uptake in stimulated SM was 5-fold higher than in non-stimulated SM. Likewise, FDG uptake was 22-fold enhanced in SM by stimulation. CPT-1 inhibition caused a 67% decrease of FTO uptake in stimulated SM, but no effect on FTO uptake by non-stimulated SM. SM uptake of FDG was not sensitive to CPT-1 inhibition in both stimulated and non-stimulated states. The data support the use of FTO and FDG for noninvasive evaluation of FAO and glucose uptake in H and SM. The reciprocal response of FTO and FDG accumulations to CPT-1 inhibition confirms the Randle effect in heart. However, FDG uptake in SM was not stimulated by CPT-1 inhibition. The dual-tracer PET imaging Methods was able to track the diverse metabolic responses to pharmacologic FAO inhibition in H and SM, and contraction-induced metabolic responses in SM.
- © 2010 by American Heart Association, Inc.