PET 2-FLUORO-2-DEOXYGLUCOSE UPTAKE IN RAT PROSTATE ADENOCARCINOMA DURING CHEMOTHERAPY WITH GEMCITABINE

This study was performed to investigate the effect of the new chemothe rapeutic agent gemcitabine on glucose transport and metabolism in pros tate carcinoma in vitro and in vivo. Methods: After transplantation of rat prostate adenocarcinoma cells, dynamic PET measurements with fluo rine-18-labeled 2-fluoro-2-deoxy-D-glucose ((18)FDG) were performed in 15 animals before and 1 day after therapy with 90 mg/kg of body weigh t (n = 8) and 180 mg/kg of body weight (n = 7) gemcitabine. In the sec ond examination, the animals received a simultaneous injection of (18) FDG and [H-3]thymidine. Quantitative evaluation of the PET data was do ne using the standardized uptake value (SUV) as well as a three-compar tment pharmacokinetic model. Furthermore, the incorporation of [H-3]th ymidine into the DNA was determined. In vitro measurements of the FDG, 3-O-methylglucose and thymidine uptake were performed immediately and 4 hr after a 24-hr incubation period with different doses of gemcitab ine, Results: FDG-SUV and the metabolic rate of FDG utilization did no t change significantly after therapy. However, the values for the tran sport rate constants K-1 and k(2) increased significantly. The incorpo ration of thymidine into the DNA of treated tumors showed an 80% decli ne as compared with a control group, In the cell culture experiments, a dose-dependent increase of FDG (up to 178%) and 3-O-methylglucose up take (up to 305%) was demonstrated. The thymidine uptake showed a 96% decline in the nucleic acid fraction and an increase of up to 337% in the cytoplasmic fraction. Conclusion: The more global measures of FDG metabolism as SUV and metabolic rate of FDG utilization were unchanged after therapy, while DNA synthesis and cell viability declined. Howev er, in vitro and in vivo evidence of an enhancement of glucose transpo rt is presented, indicating that quantification by modeling may be sup erior for the evaluation of metabolic effects during chemotherapy.