Uptake of ¹⁸F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation

Abstract

We are developing a methodology for the noninvasive imaging of glucose transport in vivo with PET and 18F-labeled 6-fluoro-6-deoxy-d-glucose (18F-6FDG), a tracer that is transported but not phosphorylated. To validate the method, we evaluated the biodistribution of 18F-6FDG to test whether it is consistent with the known properties of glucose transport, particularly with regard to insulin stimulation of glucose transport. Methods Under glucose clamp conditions, rats were imaged at the baseline and under conditions of hyperinsulinemia. Results The images showed that the radioactivity concentration in skeletal muscle was higher in the presence of insulin than at the baseline. We also found evidence that the metabolism of 18F-6FDG was negligible in several tissues. Conclusion 18F-6FDG is a valid tracer that can be used in in vivo transport studies. PET studies performed under glucose clamp conditions demonstrated that the uptake of nonphosphorylated glucose transport tracer 18F-6FDG is sensitive to insulin stimulation.

A new Michaelis–Menten‐based kinetic model for transport and phosphorylation of glucose and its analogs in skeletal muscle

“…20) and that of phosphorylation by hexokinase K H g is set to 0.13 mM. 21 As the Michaelis constant for 6FDG transport (K G 6FDG ) has not yet been determined, we made a preliminary estimate of 10 mM based on published 22 and unpublished experimental data. Also, we assume that the Michaelis constant of 2FDG transport (K G 2FDG ) is 8 mM based on unpublished experimental data and that of phosphorylation by hexokinase K H 2FDG equals 0.17 mM.…”

“…21 For both basal and EH conditions, plasma glucose concentration (P g ) was set to 6 mM, consistent with our prior experimental data in the rat. 22 IS g was specified as 85% of P g (¼5.1 mM) and 50% of P g (¼3 mM) for basal and EH conditions, respectively. 19 From the skeletal muscle blood flow in rats, 23 we assume k 1 ¼ 0.04 min À1 for basal conditions.…”

Human radiation dosimetry of 6‐[18F]FDG predicted from preclinical studies

“…[1][2][3]5 We also developed a new model for the quantitative analysis of 6-[ 18 F]FDG concentration time-courses measured using PET imaging and confirmed that the model predicts that insulin and hyperglycemia lead to increased glucose transport with insulin causing an increase and hyperglycemia causing a decrease in intracellular concentrations of the tracer. 4 Taken together, these studies demonstrate the potential for using 6-[ 18 F]FDG to measure in vivo glucose transport at the tissue level and in a minimally invasive way.…”

“…18 F]FDG preparation 6-[ 18 F]FDG was synthesized from the 3,5-O-benzylidene-6-deoxy-1,2-O-isopropylidene-6-(4 -methylbenzene)sulfonyl oxy-alpha-D-glucofuranose precursor using modification of a previously described method 1,6 and using a GE Healthcare TRACERlab FX F-N automated synthesis module. The resulting product was purified using combined C-18 and neutral Alumina Sep-Paks (Waters Corporation) and was formulated in sterile water for intravenous injection.…”

“…18 F]FDG in a series of studies and have shown that it is transported similarly to glucose by both facilitative glucose transporters (GLUTs) and sodium-dependent cotransporters (SGLTs), 3 its uptake in skeletal muscle is sensitive to insulin stimulation, 1 its uptake in skeletal muscle is competitively inhibited by hyperglycemia, 5 there are few radioactive metabolites appearing over the time-scale of PET imaging, 2 6FDG distributes in body water, 3 and urinary excretion of 18 F is slow [6% in 6 h (Ref.…”