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Department of Nuclear Medicine, Cancer Research Campaign Clinical Magnetic Resonance Research Group, and Cancer Research Campaign Centre for Cancer Therapeutics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom
Many studies suggest that changes in the uptake of the glucose analog FDG after therapy, compared with pretreatment uptake, predicts tumor response to therapy. However, clinical interpretation is compromised by a limited understanding of the effect of therapy on FDG and 2-deoxy-D-glucose (DG) uptake at the tumor cell level. Methods: Uptake of 2-deoxy-D-[1-3H]glucose (3H-DG) by SW620 colonic tumor cells was measured before and 8, 16, 24, and 48 h after treatment with the novel platinum drug oxaliplatin and the novel thymidylate synthase inhibitor Tomudex. Glucose transport was determined by measuring the initial rate of uptake of the nearly nonmetabolized glucose analog 3-O-methyl-D-[1-3H]glucose (3H-OMG). The effect of these drugs on cell cycle kinetics was determined using flow cytometry. Results: Treatment of SW620 cells with oxaliplatin was found to decrease uptake of 3H-DG after up to 24 h, but uptake returned to control levels after longer treatment. The initial decrease in 3H-DG incorporation was associated with a lower rate of glucose transport. Treatment of cells with Tomudex induced an increase in 3H-DG uptake that depended on treatment duration. Both glucose transport and the volume of distribution of 3H-OMG were higher in Tomudex-treated cells than in control cells. Flow cytometry showed that oxaliplatin induced a G2 and M arrest, whereas a buildup of cells in the S phase was associated with Tomudex treatment. Both treatments induced apoptosis in SW620 cells. Conclusion: Changes in uptake of DG by SW620 colonic tumor cells responding to therapy is specific to the drug type. Modulation of glucose transport was associated with changes in 3H-DG uptake.
Key Words: tumor • chemotherapy • 2-deoxy-D-glucose
Received Nov. 5, 1999; revision accepted Mar. 28, 2000.
For correspondence or reprints contact: Timothy A.D. Smith, PhD, MRC Cyclotron Unit, Hammersmith Hospital, Du Canc Rd., London W120NN, UK.
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