Active and passive mechanisms of [fluorine-18] fluorodeoxyglucose uptake by proliferating and prenecrotic cancer cells in vivo: a microautoradiographic study.

UNLABELLED: In this study, [18F]FDG uptake mechanisms were investigated in neoplastic cells during cell proliferation and cell death.
METHODS: Detailed analysis was performed on mouse tumor models of different growth rates using [18F]FDG, [6-13H]thymidine [3H]Thd (a precursor of DNA synthesis) and [125I]bovine serum albumin ([125I]BSA) (a marker of diffusion) with autoradiographic and histopathologic techniques and electron microscopy.
RESULTS: The three compounds, [18F]FDG, [3H]Thd and [125I]BSA, showed different heterogeneous patterns of distribution within tumor tissue sections in neoplastic and non-neoplastic cellular elements. The uptake of [18F]FDG by prenecrotic (or necrobiotic) tumor cells surrounding focal necrotic cell debris was 1.5 to 2.3 times higher than that of viable tumor cells. Prenecrotic cells did not retain trapped [18F]FDG; therefore, the uptake was considered to be nonmetabolic. Inconspicuous cell membrane, vesicular cytoplasmic organelles and condensed nuclear chromatin were remarkable findings in the prenecrotic cells. A comparison of viable tumor cells in tumors undergoing different growth rates showed that the ratio of [18F]FDG uptake was similar to that of [3H]Thd uptake in each S-phase cell. Fluorine-18-FDG showed a cell cycle dependency, with a higher uptake observed in cells in G0/G1 and G2 phases of the cell cycle compared with the S and M phases.
CONCLUSION: A passive mechanism of [18F]FDG uptake may exist in the necrobiotic/prenecrotic or hypoxic/anoxic cells in tumors. However, the discordance of [18F]FDG and [3H]Thd uptake may be the result of the different cell cycle dependency of tracer uptake in the same tumor.