Glycolysis-Induced Discordance between Glucose Metabolic Rates Measured with Radiolabeled Fluorodeoxyglucose and Glucose

Abstract

Summary: We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMR_glc (LCMR_glc), using sequentially administered [¹⁸F]fluorodeoxyglucose (FDG) and [¹⁴C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GM_g) and oxidative (GM₀) glucose metabolism and is therefore related to total cerebral glucose metabolism GM_t: GM_g + GM₀ = GM_t. With oxidative metabolism, the ¹⁴C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the ¹⁴C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GM₀ than to GM_V If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMR_glc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.