The Effects of Capecitabine Treatment on the Uptake of Thymidine Analogue: 18F-FAU, 18F-FMAU, and 18F-FLT
Reinoehl, Mary Alice
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Capecitabine, a chemotherapeutic prod rug of fluorouracil (FU), is currently approved for use with metastatic breast and colorectal cancer. Once absorbed, capecitabine inhibits thymidylate synthase, an enzyme that generates thymidine monophosphate and consequently thymidine triphosphate. Additionally, it disrupts RNA function and incorporates into DNA where it ceases DNA prolongation. Further exploration into its activation, mechanisms of cytotoxicity and metabolism will provide drug kinetic information that could be used to predict treatment response. Results from previous studies have indicated that capecitabine interferes with thymidine synthesis and its DNA incorporation pathway, suggesting that it may alter the uptake of thymidine analogs used in positron emission tomography (PET) imaging. Studying thymidine analogs would provide an over~ll idea of the workings of capecitabine within tumor cells. The aim of this study is to compare and contrast the uptake of three thymidine analogs 18F-FLT, l8F-FAU, and l8F-FMAU in patients with metastatic breast and colo rectal cancer while receiving capecitabine therapy. Studying patients with each of these tracers will provide important information on the affects of capecitabine on cellular metabolism, growth and DNA synthesis pathways. Fourteen patients at the Karmanos Cancer Institute in Detroit, Michigan underwent two PET scans, once before therapy and approximately one week after. The tumor uptakes of these agents were measured in Standardized Uptake Value (SUV) and compared after therapy. Further kinetic analysis and percent differences after therapy were computed using the PMOD v3.15 program. The results indicated 18F-FLT to be the most effective tumor response predictor with an average SUVmean percent difference after therapy of 63% effectiveness compared to 2% and 0.316% for 18F-FAU and -l8F-FMAU; respectively. The differences in uptake may be used in the future to help predict response to treatment after one dosage of capecitabine treatment.