18 F‐Fluorothymidine‐Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns

Introduction . PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18 F‐FDG‐PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal‐to‐noise intensity. 18 F‐Fluorothymidine (FLT) in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18 F‐FLT‐PET in a GBM mouse model, especially after radiation therapy (RT), and its correlation with useful biomarkers, including proliferation and DNA damage. Methods . Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18 F‐FDG and 18 F‐FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki‐67), DNA damage and repair ( γ H2AX), hypoxia (HIF‐1 α ), and angiogenesis (VEGF). Results . We confirmed that 18 F‐FLT‐PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18 F‐FLT‐PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions . 18 F‐FLT‐PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.