Effect of hyperglycemia on in vitro tumor uptake of tritiated FDG, thymidine, L-methionine and L-leucine

We have previously demonstrated in vitro and in vivo that tumor uptake of FDG is markedly diminished by acute hyperglycemia. This in vitro study was designed to determine if tumor uptake of PET tracers (FDG, thymidine, L- methionine and L-leucine) is affected by acute or chronic hyperglycemia. Methods: Human ovarian adenocarcinoma (HTB 77 IP3) cells were grown in media containing 100 or 300 mg/dl of glucose. At 7, 20, 38, 51 and 72 days after initial culture, uptake of ³H-labeled FDG, thymidine, L-methionine and L- leucine into the cells was determined in the presence of 100 or 300 mg/dl of glucose. Results: With acute hyperglycemia (300 mg/dl of glucose), the percent decreases in uptake of FDG, thymidine, methionine and leucine were 76.7%, 22.4%, 7.4% and 11.1%, respectively, as compared to assay at 100 mg/dl of glucose (mean day 51 and day 72 data). Significant decreases were observed in FDG and thymidine uptake with acute hyperglycemia (p < 0.0005). When cells grown at 300 mg/dl of glucose for 51 and 72 days were assayed at 100 mg/dl of glucose, the mean percent decreases in uptake of these tracers were 10.4%, 7.8%, 8.0% and 16.8%, respectively, as compared to cells grown and assayed at 100 mg/dl of glucose. No significant decrease was observed in tumor uptake of these tracers, except for leucine (p < 0.05). Conclusion: These human adenocarcinoma cells do not significantly change FDG uptake with chronic hyperglycemia while acute hyperglycemia markedly reduces uptake of FDG and thymidine. Neither methionine nor leucine uptake is significantly affected by acute hyperglycemia. To optimally evaluate tumor biology by PET, the fasting state seems necessary for FDG and thymidine studies, while methionine or leucine appears more suitable for hyperglycemic patients.