Abstract
ObjectiveAmong different PET tracers, 18F-fludeoxyglucose (FDG) and 11C-choline are known to have a high tumor uptake correlated with a high mitotic index of tumor cells. Thus, the uptake of 18F-FDG and 11C-choline may be dependent on the cell cycle. In the present study, we examined the uptake of 18F-FDG and 11C-choline in cancer cell lines by cell cycle synchronization to clarify the biological properties of cancer cells with respect to each tracer.MethodsHeLa S3 Cells were synchronized by the double thymidine (TdR) block methods. 18F-FDG and 11C-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.ResultsThe uptake of 18F-FDG was the highest in S to G2/M phases, and markedly decreased in G1 phase. The uptake of 11C-choline reached its peak in G2/M, and decreased in G1 phase. The level of GLUT1 expression was similar to that of 18F-FDG uptake during the cell cycle, and the level of CTL1 expression was similar to that of 11C-choline uptake throughout the cell cycle.ConclusionsIn this in vitro study, we demonstrated that 18F-FDG and 11C-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 18F-FDG and 11C-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 18F-FDG and 11C-choline accumulation seem to be caused by the above properties of these transporters.
Highlights
PET is a diagnostic imaging modality in nuclear medicine that utilizes radioactive tracers with specific uptake in cancer cells. 18F-fluorodeoxyglucose (FDG) is the most common tracer and detects increased glucose metabolism in cancer cells [1]. 11C-choline is another tracer that detects phospholipid metabolism in the cell
Data obtained by Flow cytometry (FCM) was analyzed using ModFit LT 2.0 to calculate the proportion of cells in G1, S, and G2/M phases in each sample with respect to time after switching to TdR-free medium
In this in vitro study, we showed that 18F-FDG and 11C-choline had the highest uptake in S to G2/M phases and in G2/M phase, respectively, with a rapid decrease in G1 phase
Summary
PET is a diagnostic imaging modality in nuclear medicine that utilizes radioactive tracers with specific uptake in cancer cells. 18F-fluorodeoxyglucose (FDG) is the most common tracer and detects increased glucose metabolism in cancer cells [1]. 11C-choline is another tracer that detects phospholipid metabolism in the cell. The uptake of 18F-FDG and 11C-choline to tumor tissue varies significantly within the same mass with identical tumor tissue and rate of progression. Hara et al [5] reported that the uptake of 11C-choline in cancer cells is proportional to the rate of the cell cycle, such that malignant tumors with a high frequency of cell division have a higher level of uptake. Glunde et al [6] demonstrated a strong correlation between the level of abnormal choline metabolism in cancer cells and disease progression over time. These findings suggest that, as with the uptake of 18F-FDG, that of 11C-choline is dependent on the cell cycle. We continuously changed the cell cycle in a human cancer cell line, HeLa S3, to examine changes in the uptake of 18FFDG and 11C-choline over time
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