Aim: We aimed to investigate whether 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]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 [(18)F]FLT. In another group of mice with HT29 cells, static PET images were obtained 110 min after [(18)F]FLT injection.
Results: Kinetic parameters related to [(18)F]FLT retention increased significantly, whereas the de-phosphorylation of [(18)F]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 [(18)F]FLT. There was a significant correlation between the tumor SUVmean and TK1 activity.
Conclusion: SUVmean at 110-120 min after [(18)F]FLT, can quantitatively evaluate kinetic parameters and TK1 activity after TS inhibition.
Keywords: 3’-deoxy-3’-[18F]fluorothymidine; 5-fluorouracil; positron emission tomography; thymidine kinase; thymidylate synthase.