Chemotherapy-induced modulation of [¹⁸F]Fluoro-2-deoxy-D-glucose incorporation at the tumour cell level

Background

Changes in the incorporation of [¹⁸F]Fluoro-2-deoxy-D-glucose (FDG) determined using positron emission tomography (PET) is a highly sensitive technique for the early detection of tumour response to therapy [1]. Using serial FDG-PET scans, tumours responding to therapy generally show a decrease in FDG incorporation compared with pretreatment. How FDG incorporation at the tumour cell level is modified by treatment and the mechanisms involved is poorly understood and is the subject of the present study.

Methods

[¹⁸F]FDG incorporation, glucose transport, hexokinase activity and ATP content were determined in breast tumour (MCF-7, T47D), colorectal (SW620, HCT-8) and gastric (AGS) tumour cell lines during response to typical and novel agents utilised in the treatment of the respective tumour types. Treatment doses causing 50% growth inhibition (IC₅₀ determined by MTT assay) over a 72-hour period were utilized.

Results

All 72-hour treatment/cell line combinations (breast tumour cells – MCF-7 and T47D – with tamoxifen, doxorubicin or docetaxel; colorectal cells – SW620 with 5FU, oxaliplatin or irinotecan – and HCT8 with irinotecan, cetuximab or both; gastric tumour cells – AGS – with cisplatin, 5 FU or epirubicin) resulted in decreased FDG incorporation compared with untreated cells. Decreased FDG incorporation most closely reflected changes in glucose transport by the HCT-8 and AGS cells, ATP content by the breast tumour cells and hexokinase activity by the SW620 cells. Apoptosis was evident in epirubicin-treated AGS cells, which showed the greatest decrease in FDG incorporation, but was also apparent in irinotecan-treated cells, which showed declines in FDG incorporation comparable with treatments without apoptotic fractions.

Conclusion

FDG incorporation in tumour cells responding to a wide variety of chemotherapy agents is decreased compared with untreated cells, suggesting that the decrease in FDG incorporation observed in the clinical setting reflects changes at the tumour cell level. The rate-limiting step varies with the tumour cell line and can be glucose transport, hexokinase activity or ATP content. Large decreases in FDG incorporation may in some tumours be indicative of the presence of apoptotic fractions.