The effects of 5-fluoruracil treatment on 3'-fluoro-3'-deoxythymidine (FLT) transport and metabolism in proliferating and non-proliferating cultures of human tumor cells.

Nuclear Medicine and Biology
David A PlotnikJeffrey L Schwartz

Abstract

3'-Fluoro-3'-deoxythymidine (FLT) positron emission tomography (PET) has been proposed for imaging thymidylate synthase (TS) inhibition. Agents that target TS and shut down de novo synthesis of thymidine monophosphate increase the uptake and retention of FLT in vitro and in vivo because of a compensating increase in the salvage pathway. Increases in both thymidine kinase-1 (TK1) and the equilibrative nucleoside transporter hENT1 have been reported to underlie this effect. We examined whether the effects of one TS inhibitor, 5-fluorouracil (5FU), on FLT uptake require proliferating cells and whether the effects are limited to increasing TK1 activity. The effects of 5FU on FLT transport and metabolism, TK1 activity, and cell cycle progression were evaluated in the human tumor cell line, A549, maintained as either a proliferating or non-proliferating culture. There were dose-dependent increases in FLT uptake that peaked after a 10 μM 5FU exposure and then declined to baseline levels or below at higher doses in both proliferating and non-proliferating cultures. The dose-dependence for FLT uptake was mirrored by changes in TK1 activity. S phase fraction did not correlate with FLT uptake in proliferating cultures. Chemical inhibition...Continue Reading

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Aug 20, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·David A PlotnikJeffrey L Schwartz

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Citations

Jun 1, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lars StelterSteven M Larson
Oct 4, 2016·Drug Discovery Today·Sarah R MuddJohn D Beaver
Nov 1, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Sandra HeskampOtto C Boerman
Jun 26, 2018·Journal of Surgical Oncology·David A Mankoff, Sharyn I Katz

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