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Title: Mechanisms of fluoro-2-deoxyglucose retention by tumour cells responding to therapy
Author: Sharma, Rituka I.
ISNI:       0000 0001 3398 4497
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2008
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Purpose: To investigate the biochemical pathways underlying therapy-induced changes in FDG uptake in tissue culture cells. Methods: Breast cancer cell lines MCF-7 (wild-type (WT), clones of 5-FU-resistant cells and a clone with stably transfected dominant negative p53 (DD)) and T47D were studied. Colon cancer cell lines, SW620 and HCT-8 were also studied. Experiments were performed with tumour cells treated with IC50 chemotherapy determined using the 3-(4,5-dimehtylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MCF-7 and T47D cells were treated with tamoxifen, doxorubicin and doectaxel; DD with doxorubicin, cisplatin and 5-FU; SW620 with 5-FU, oxaliplatin and irinotecan and HCT-8 cells with irinotecan and cetuximab. 18F-FDG incorporation was determined following treatment for 24, 48 or 72 hours and related to cell cycle changes, glucose transport, hexokinase activity and ATP content. Results: MCF-7 cells showed decreased 18F-FDG incorporation and ATP levels with each 72 hour treatment. Hexokinase activity was reduced in tamoxifen-treated cells whilst glucose transport decreased with doxorubicin and tamoxifen. T47D cells showed decreased 18F-FDG incorporation and ATP levels with each 72 hour treatment. 18F-FDG incorporation decreased and glucose transport increased in MCF-7FU1 and MCF-7FU5 cells, compared with sensitive cells. DD cells showed increased ATP levels, 18F-FDG incorporation and glucose transport, compared with WT cells. 18F-FDG incorporation decreased in cisplatin and doxorubicin-treated DD cells and cisplatin-treated WT cells. SW620 cells showed decreased 18F-FDG incorporation and hexokinase activity with each 72 hour treatment. 18F-FDG incorporation by HCT-8 cells decreased following treatment with irinotecan and cetuximab alone and combined. Conclusion: 18F-FDG uptake is mainly influenced by the type of cells, the length of exposure to a drug and the type of drug administered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available