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.

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.

• Authors: Yolanda Piña, Christina Decatur, Timothy G Murray, Samuel K Houston, Milena Lopez-Cavalcante, Eleut Hernandez, Magda Celdran, Nikesh Shah, William Feuer, Theodore Lampidis
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 2 Pg. 996-1002 (Feb 2012) ISSN: 1552-5783 [Electronic] United States
• PMID: 22266512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

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