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Colorectal Tumor Cells Treated with 5-FU, Oxaliplatin, Irinotecan, and Cetuximab Exhibit Changes in ¹⁸F-FDG Incorporation Corresponding to Hexokinase Activity and Glucose Transport

School of Medical Sciences (Biomedical Physics), University of Aberdeen, Foresterhill, Aberdeen, United Kingdom

Correspondence: For correspondence or reprints contact: Tim A.D. Smith, Biomedical Physics School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K. E-mail: t.smith{at}abdn.ac.uk

The purpose of this study was to determine therapy-induced changes in ¹⁸F-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in ¹⁸F-FDG incorporation. Methods: SW620 cells were treated with inhibitory concentration of 50% (IC₅₀) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC₅₀ doses of irinotecan, cetuximab, and irinotecan plus cetuximab. ¹⁸F-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells. Results: Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. ¹⁸F-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased ¹⁸F-FDG incorporation. Decreased ¹⁸F-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased ¹⁸F-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment. Conclusion: ¹⁸F-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC₅₀ doses of cetuximab also exhibit decreased ¹⁸F-FDG.

Key Words: oncology • PET • cetuximab • colorectal • ¹⁸F-FDG • glucose transport

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