Retinoblastoma treatment: Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors

Abstract

PURPOSE. To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-D-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH BETAT AG retinal tumors. METHODS. Seventeen-week-old LH BETAT AG retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels. RESULTS. Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95% reduction (P