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Yolanda Piña, Christina Decatur, Timothy G. Murray, Samuel K. Houston, Milena Lopez-Cavalcante, Eleut Hernandez, Magda Celdran, Nikesh Shah, William Feuer, Theodore Lampidis; Retinoblastoma Treatment: Utilization of the Glycolytic Inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to Target the Chemoresistant Hypoxic Regions in LHBETATAG Retinal Tumors. Invest. Ophthalmol. Vis. Sci. 2012;53(2):996-1002. doi: 10.1167/iovs.11-8265.
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To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-d-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LHBETATAG retinal tumors.
Seventeen-week-old LHBETATAG 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.
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 < 0.001).
This is the first study to elucidate that 2-FG treatment in retinoblastoma produces an impact on hypoxia and a concomitant decrease on tumor burden. In this study, the authors validate their previous studies by revealing that glycolytic inhibitors effectively target hypoxia in retinoblastoma tumors. The future application of 2-FG as an adjuvant treatment to standard chemotherapy may enhance the treatment of retinoblastoma.
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