Retinoblastoma treatment: utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-D-glucose (2-FG), to target the chemoresistant hypoxic regions in LH(BETA)T(AG) retinal tumors

Invest Ophthalmol Vis Sci. 2012 Feb 27;53(2):996-1002. doi: 10.1167/iovs.11-8265. Print 2012 Feb.

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(BETA)T(AG) retinal tumors.

Methods: Seventeen-week-old LH(BETA)T(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 < 0.001).

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Glycolysis / drug effects*
  • Hypoxia / drug therapy*
  • Mice
  • Neoplasms, Experimental
  • Radiopharmaceuticals / pharmacokinetics
  • Retinal Neoplasms / blood supply
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / blood supply
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / pathology
  • Treatment Outcome
  • Tumor Burden / drug effects*

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18