3'-Deoxy-3'-[F-18]Fluorothymidine Positron Emission Tomography Imaging of Thymidine Kinase 1 Activity After 5-Fluorouracil Treatment in a Mouse Tumor Model

Abstract

Aim: We aimed to investigate whether 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) positron emission tomography (PET) can estimate thymidine kinase 1 (TK1) activity after thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) in a mouse tumor model. Materials and Methods: Nude mice with HT29 tumors were injected with phosphate-buffered saline or 5-FU (16.7 or 50 mg/kg). Twenty-four hours later, 2-hour dynamic images were acquired after injection of [F-18]FLT. In another group of mice with HT29 cells, static PET images were obtained 110 min after [F-18]FLT injection. Results: Kinetic parameters related to [F-18]FLT retention increased significantly, whereas the de-phosphorylation of [F-18]FLT monophosphate decreased significantly. The standardized uptake value (SUVmean) of HT29 tumors correlated significantly with the net influx constant and the distribution volume for phosphorylated [F-18]FLT. There was a significant correlation between the tumor SUVmean and TK1 activity. Conclusion: SUVmean at 110-120 mm after [F-18]FLT, can quantitatively evaluate kinetic parameters and TK1 activity after TS inhibition.