Key result
In stimulated rat skeletal muscle, 18F-FTO and 18F-FDG uptakes increased 4.4- and 28-fold, respectively, with CPT-1 inhibition decreasing 18F-FTO uptake by 66%.
Why the study?
Evaluating fatty acid oxidation rates by PET has been limited by the lack of a suitable probe, hindering the noninvasive study of fat-carbohydrate metabolic switching in heart and skeletal muscle.
18F-FTO is a viable FAO-dependent PET probe that, alongside 18F-FDG, can noninvasively assess metabolic switching between fat and carbohydrate oxidation in the heart and skeletal muscle.
Supports 18F-FTO development as FAO PET probe in muscle; leaves open human cardiac validation.
The ability of heart and skeletal muscle (SM) to switch between fat and carbohydrate oxidation is of high interest in the study of metabolic diseases and exercise physiology. Positron emission tomography (PET) imaging with the glucose analog 2-[ 18 F]fluoro-2-deoxy-glucose ( 18 F-FDG) provides a noninvasive means to quantitate glucose metabolic rates. However, evaluation of fatty acid oxidation (FAO) rates by PET has been limited by the lack of a suitable FAO probe. We have developed a metabolically trapped oleate analog, ( Z)-18-[ 18 F]fluoro-4-thia-octadec-9-enoate ( 18 F-FTO), and investigated the feasibility of using 18 F-FTO and 18 F-FDG to measure FAO and glucose uptake, respectively, in heart and SM of rats in vivo. To enhance the metabolic rates in SM, the vastus lateralis (VL) muscle was electrically stimulated in fasted rats for 30 min before and 30 min following radiotracer injection. The responses of radiotracer uptake patterns to pharmacological inhibition of FAO were assessed by pretreatment of the rats with the carnitine palmitoyl-transferase-1 (CPT-1) inhibitor sodium 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate (POCA). Small-animal PET images and biodistribution data with 18 F-FTO and 18 F-FDG demonstrated profound metabolic switching for energy provision in the myocardium from exogenous fatty acids to glucose in control and CPT-1-inhibited rats, respectively. Uptake of both radiotracers was low in unstimulated SM. In stimulated VL muscle, 18 F-FTO and 18 F-FDG uptakes were increased 4.4- and 28-fold, respectively, and CPT-1 inhibition only affected 18 F-FTO uptake (66% decrease). 18 F-FTO is a FAO-dependent PET probe that may allow assessment of energy substrate metabolic switching in conjunction with 18 F-FDG and other metabolic probes.
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DeGrado et al. (2018) studied this question. 18F-FTO and 18F-FDG PET imaging vs. Control rats / unstimulated muscle was evaluated on Radiotracer uptake in heart and skeletal muscle. In stimulated rat skeletal muscle, 18F-FTO and 18F-FDG uptakes increased 4.4- and 28-fold, respectively, with CPT-1 inhibition decreasing 18F-FTO uptake by 66%.
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