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

Objective: Among different PET tracers, F-fludeoxyglucose (FDG) and C-choline are known to have a high tumor uptake correlated with a high mitotic index of tumor cells. Thus, the uptake of F-FDG and C-choline may be dependent on the cell cycle. In the present study, we examined the uptake of F-FDG and C-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-FDG and C-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-FDG was the highest in S to G2/M phases, and markedly decreased in G1 phase. The uptake of C-choline reached its peak in G2/M, and decreased in G1 phase. The level of GLUT1 expression was similar to that of F-FDG uptake during the cell cycle, and the level of CTL1 expression was similar to that of C-choline uptake throughout the cell cycle.

Conclusions: In this in vitro study, we demonstrated that F-FDG and C-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-FDG and C-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-FDG and C-choline accumulation seem to be caused by the above properties of these transporters.