title: 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: OBJECTIVE
  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.affiliation: Bascom Palmer Eye Institute, Miami, Florida 33101, USA.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Piña
authors.forename: Christina
authors.initials: C
authors.lastname: Decatur
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Murray
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Houston
authors.forename: Milena
authors.initials: M
authors.lastname: Lopez-Cavalcante
authors.forename: Eleut
authors.initials: E
authors.lastname: Hernandez
authors.forename: Magda
authors.initials: M
authors.lastname: Celdran
authors.forename: Nikesh
authors.initials: N
authors.lastname: Shah
authors.forename: William
authors.initials: W
authors.lastname: Feuer
authors.forename: Theodore
authors.initials: T
authors.lastname: Lampidis
mesh_terms: D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006019:Glycolysis / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy*; D051379:Mice; D009374:Neoplasms, Experimental; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D019572:Retinal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18