FDG for therapy of metabolically active tumors

(18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG, later referred to as (19)FDG) has been extensively used in diagnostic positron emission tomography (PET) in oncology for many years. FDG is a glucose analog that is taken by cells in a similar fashion as glucose and is phosphorylated by hexokinase to (18)F-FDG-6-phosphate but cannot undergo further glycolysis, and hence is trapped in the cell. Metastatic cancer remains a major cause of death men and women, surpassed only by heart disease. Despite the enormous research efforts resulting in emergence of novel drug candidates, there is little progress in improving the survival of patients with many types of solid tumors. Thus, novel therapies to combat metastatic cancer are urgently needed. With a physical half-life of almost 2 hours, (18)F emits energetic positrons with high abundance (96%) and a path length in tissue of ∼0.1-0.2 cm. Theoretically, these positrons can kill cancer cells in the same manner as electrons by damaging DNA and cellular machinery and inducing apoptosis/necrosis of the tumor cells. Several years ago, we explored, in a first series of comprehensive studies, the therapeutic potential of FDG in experimental breast cancer and showed its efficacy and safety. Since then, FDG therapy has been shown to be effective and safe in experimental melanoma, colon cancer, as well as in eliminating in vitro the endothelial cells in blood vessels, which supply the tumors with nutrients. The next step forward in translation of FDG therapy into the clinic should be a phase II clinical trial. Also, recent developments in targeted PET imaging could increase the range of PET pharmaceuticals potentially useful for positron therapy of metastatic cancers because of increased specificity of these tracers in comparison with FDG.