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Anticancer Res. 2014 Feb;34(2):759-66.

3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging of thymidine kinase 1 activity after 5-fluorouracil treatment in a mouse tumor model.

Author information

1
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea. dhmoon@amc.seoul.kr.

Abstract

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

PMID:
24511010
[Indexed for MEDLINE]
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