Low brain FDG uptake in lymphoma patients represents preferential use of high blood lactate released by total lesion glycolysis.

1683 Objectives: Positron emission tomography (PET) not infrequently displays strikingly low brain 18F-fluoro-2-deoxyglucose (FDG) uptake in lymphoma patients who do not have any cerebral abnormality. In this study, we clarified the clinical factors that determine cerebral FDG uptake level in such patients, with focus on the role of blood lactate and glucose concentrations and size of glycolytic tumor burden. Methods: We analyzed FDG PET of 129 patients with non-Hodgkin’s lymphoma who had blood glucose and lactate measurements on the same day of PET. Average standardized uptake value (SUVave) of the cerebral cortex was compared to major clinical variables including blood glucose and lactate concentrations, and total lesion glycolysis (TLG) of all lymphoma lesions in the torso. Results: Brain FDG uptake was low (SUVave < 4.0) in 81 of our study population (62.8%). This group was significantly older, had worse ECOG performance and IPI risk scores, greater Ann Arbor stage, and higher blood glucose and lactate concentrations compared to those with normal brain FDG uptake (SUVave ≥ 4.0). In the entire study population, temporal cortex SUVave was inversely correlated with ECOG and IPI scores, lymphoma stage, and blood glucose and lactate levels. Furthermore, log TLG, was linearly correlated with blood lactate concentration and inversely correlated with log temporal cortex SUVave. Multivariate linear regression analysis revealed that blood glucose level, log blood lactate level, and log tumor TLG were significant independent explanatory variables that determine brain SUVave level. Conclusions: Low FDG uptake in the brain of lymphoma patients represents cerebral glucose sparing by concentration-dependent preferential utilization of lactate elevated in the blood. The latter in turn, is produced in proportion to the total glycolytic tumor burden in the body. This illustrates how shifting of brain energy substrate by the Warburg effect can be visualized by FDG PET/CT.