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Active and Passive Mechanisms of [Fluorine-18] Fluorodeoxyglucose Uptake by Proliferating and Prenecrotic Cancer Cells In Vivo: A Microautoradiographic Study

Departments of Nuclear Medicine and Radiology and Pharmacology, Institute for Aging, Development and Cancer
Cyclotron and Radioisotope Center, Tohoku University
Clusterecore Institute of Biology, Sendai, Japan

Correspondence: For correspondence or reprints contact: Roko Kubota, PhD, Department of Nuclear Medicine and Radiology, Institute for Aging, Development and Cancer, Tohoku University, 4-1 Seiryo-cho, Aoba-ku, Sendai 980, Japan.

ABSTRACT

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, [6-³H]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 [¹²⁵]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 [¹⁸]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.

Key Words: [fluorine-18] fluorodeoxyglucose • cancer • autoradiography • cell cycle • tritiated thymidine

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