Determination of the lumped constant for [18F] fluorodeoxyglucose in human skeletal muscle

Quantitative [18F]fluorodeoxyglucose (FDG) PET has considerable potential for the study of the physiology of skeletal muscle glucose metabolism and for the assessment of perturbations associated with insulin resistance in skeletal muscle. This application of FDG PET imaging depends in part on the determination of the analog effects of FDG relative to true glucose with respect to skeletal muscle. Deoxyglucose has a higher affinity for transporters than glucose and a lower affinity for hexokinase. This study was undertaken to assess the lumped constant (LC) for skeletal muscle, determined empirically as the quotient of FDG metabolism to that of [3H]glucose ([3H]G), and to assess whether the LC is affected by insulin, which is the principal hormonal regulator of glucose metabolism in muscle.

Seventeen healthy lean volunteers were randomly assigned and were studied at insulin infusion rates of 0, 20, 40 and 120 mU/min/m2 body surface area. After attaining steady-state euglycemic conditions, injections of FDG and [3H]G were given, and the fractional extraction (E) for each compound across the leg was measured by arterial and venous sampling for 90 min. The LC was calculated as the ratio of the respective fractional extractions (LC = E(FDG)/E[3H]G).

During fasting conditions (i.e., absence of insulin infusion), the LC for skeletal muscle was slightly greater than 1. Insulin had a robust effect to increase fractional extractions of both FDG and [3H]G. The effect was symmetrical for the two compounds, and, hence, the LC did not change significantly in response to progressive insulin stimulation. The mean value of the LC across insulin doses for human skeletal muscle was 1.23 +/- 0.05.

Direct comparison of [3H]G and FDG metabolism during insulin-stimulated conditions, across the in vivo tissue bed of skeletal muscle 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 and that insulin did not alter the LC in skeletal muscle.