FUNDAMENTAL LIMITATIONS OF [F-18] 2-DEOXY-2-FLUORO-D-GLUCOSE FOR ASSESSING MYOCARDIAL GLUCOSE-UPTAKE

Background The glucose tracer analog [F-18]2-deoxy-2-fluoro-D-glucose (FDG) is widely used for assessing regional myocardial glucose metabol ism in vivo. The reproducibility of this method has recently been ques tioned because of a discordant affinity of hexokinase for its substrat es glucose and 2-deoxyglucose. We therefore compared rates of glucose utilization simultaneously with tissue time-activity curves of FDG upt ake before and after changes in the physiological environment of the h eart. Methods and Results Isolated working rat hearts were perfused fo r 60 minutes with recirculating Krebs buffer containing glucose (10 mm ol/L), FDG (1 mu Ci/mL), [2-H-3]glucose (0.05 mu Ci/mL), and [U-C-14]2 -deoxyglucose (2-DG; 0.025 mu Ci/mL). Myocardial glucose uptake was me asured by tracer ([2-H-3]glucose) and tracer analog methods (FDG and 2 -DG) before and after the addition of either insulin (1 mU/mL), epinep hrine (1 mu mol/L), lactate (40 mmol/L), or D,L-beta-hydroxybutyrate ( 40 mmol/L) at 30 minutes of perfusion and after acute changes in cardi ac workload. Under steady-state conditions, myocardial rates of glucos e utilization as measured by tritiated water ((H2O)-H-3) production fr om metabolism of [2-H-3]glucose, FDG uptake, and 2-DG retention were l inearly related. The addition of competing substrates decreased glucos e utilization immediately. The addition of insulin increased the rate of glucose utilization as measured by the glucose tracer but not as me asured by the tracer analogs. The ratio of (H2O)-H-3 release/myocardia l FDG uptake increased by 111% after the addition of insulin, by 428% after the addition of lactate, and by 232% after the addition of beta- hydroxybutyrate. Epinephrine increased rates of glucose utilization an d contractile performance, whereas there was no increase in glucose up take with a comparable increase in workload alone. There was no change in the relation between the glucose tracer and the tracer analog eith er with epinephrine or with acute changes in workload. Conclusions The uptake and retention of FDG in heart muscle is linearly related to gl ucose utilization only under steady-state conditions. Addition of insu lin or of competing substrates changes the relation between uptake of the glucose tracer and FDG. These observations preclude the determinat ion of absolute rates of myocardial glucose uptake by the tracer analo g method under non-steady-state conditions.