Phosphorylation status of thymidine kinase 1 following antiproliferative drug treatment mediates 3'-deoxy-3'-[18F]-fluorothymidine cellular retention.

ABSTRACT:

Background

3'-Deoxy-3'-[18F]-fluorothymidine ([18F]FLT) is being investigated as a Positron Emission Tomography (PET) proliferation biomarker. The mechanism of cellular [18F]FLT retention has been assigned primarily to alteration of the strict transcriptionally regulated S-phase expression of thymidine kinase 1 (TK1). This, however, does not explain how anticancer agents acting primarily through G2/M arrest affect [18F]FLT uptake. We investigated alternative mechanisms of [18F]FLT cellular retention involving post-translational modification of TK1 during mitosis.

Methods

[18F]FLT cellular retention was assessed in cell lines having different TK1 expression. Drug-induced phosphorylation of TK1 protein was evaluated by MnCl2-phos-tag gel electrophoresis and correlated with [18

SUBMITTER: Sala R 

PROVIDER: S-EPMC4086825 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature