18F-FDG and 11C-choline uptake in proliferating tumor cells is dependent on the cell cycle in vitro

Objective Among different PET tracers, F-18-fludeoxyglucose (FDG) and C-11-choline are known to have a high tumor uptake correlated with a high mitotic index of tumor cells. Thus, the uptake of F-18-FDG and C-11-choline may be dependent on the cell cycle. In the present study, we examined the uptake of F-18-FDG and C-11-choline in cancer cell lines by cell cycle synchronization to clarify the biological properties of cancer cells with respect to each tracer. Methods HeLa S3 Cells were synchronized by the double thymidine (TdR) block methods. F-18-FDG and C-11-choline were administered to synchronized cells, and the radioactivity per cell was measured to compare the cellular uptake of the tracers during S, G2/M, and G1 phases. Flow cytometry (FCM) was performed to measure the proportion of cells in G1, S, and G2/M phases. Furthermore, the levels of glucose transporter 1 (GLUT1) and choline transporter-like protein 1 (CTL1) in the cell were evaluated by FCM. Results The uptake of F-18-FDG was the highest in S to G2/M phases, and markedly decreased in G1 phase. The uptake of C-11-choline reached its peak in G2/M, and decreased in G1 phase. The level of GLUT1 expression was similar to that of F-18-FDG uptake during the cell cycle, and the level of CTL1 expression was similar to that of C-11-choline uptake throughout the cell cycle. Conclusions In this in vitro study, we demonstrated that F-18-FDG and C-11-choline had the highest uptake in S to G2/M phases and in G2/M phase, respectively, with a rapid decrease in G1 phase. These findings suggest that F-18-FDG and C-11-choline have a high accumulation in tumor cells with a high mitotic index. Furthermore, our study suggests that the expression of GLUT1 and CTL1 has cell cycle dependence, and the changes of F-18-FDG and C-11-choline accumulation seem to be caused by the above properties of these transporters.