Effect of MAPK inhibition on cell cycle regulation of thymidine kinase 1 and [18F]-FLT PET

Abstract

Positron emission tomography (PET) imaging using the radiotracer 3’-deoxy-3’-[18F]fluorothymidine ([18F]-FLT) has shown potential as a biomarker of proliferation in tumors. [18F]-FLT measures the activity of thymidine kinase 1 (TK1), which is related to cell proliferation. The relationship between [18F]-FLT uptake and TK1 regulation is complex and, to date, not sufficiently understood. This is particularly true in cancer where cell cycle regulation is often abnormal. If FLT PET is to serve as a biomarker of proliferation then it is vital to understand the underlying biological events responsible for the [18F]-FLT retention and such an understanding begins with how cancer cells regulate TK1. Therefore, the goal of this research is to understand cellular mechanisms of TK1 regulation in cancer cells. These studies have focused on colorectal cancer (CRC) and therapeutic blockade of the epidermal growth factor receptor (EGFR) signaling axis.