Determination of the lumped constant for [F-18]fluorodeoxyglucose in humanskeletal muscle

Quantitative [F-18]fluorodeoxyglucose (FDG) PET has considerable potential for the study of the physiology of skeletal muscle glucose metabolism and f or the assessment of perturbations associated with insulin resistance in sk eletal muscle. This application of FDG PET imaging depends in part on the d etermination of the analog effects of FDG relative to true glucose with res pect to skeletal muscle. Deoxyglucose has a higher affinity for transporter s than glucose and a lower affinity for hexokinase. This study was undertak en to assess the lumped constant (LC) for skeletal muscle, determined empir ically as the quotient of FDG metabolism to that of [H-3]glucose ([H-3]G), and to assess whether the LC is affected by insulin, which is the principal hormonal regulator of glucose metabolism in muscle. Methods: Seventeen hea lthy lean volunteers were randomly assigned and were studied at insulin inf usion rates of 0, 20, 40 and 120 mU/min/m(2) body surface area. After attai ning steady-state euglycemic conditions, injections of FDG and [H-3]G were given, and the fractional extraction (E) for each compound across the leg w as measured by arterial and venous sampling for 90 min. The LC was calculat ed as the ratio of the respective fractional extractions (LC = E-FDG/E-[3H] G). Results: During fasting conditions (i.e., absence of insulin infusion), the LC for skeletal muscle was slightly greater than 1. Insulin had a robu st effect to increase fractional extractions of both FDG and [H-3]G. The ef fect was symmetrical for the two compounds, and, hence, the LC did not chan ge significantly in response to progressive insulin stimulation. The mean v alue of the LC across insulin doses for human skeletal muscle was 1.23 +/- 0.05. Conclusion: Direct comparison of [H-3]G and FDG metabolism during ins ulin-stimulated conditions, across the in vivo tissue bed of skeletal muscl e in the leg with both tracers given in an identical manner, yielded an LC value of 1.2, indicating that there was modest preferential uptake of FDG a nd that insulin did not alter the LC in skeletal muscle.