L-Buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice

Academic Article

Abstract

  • An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 ╬╝mol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy.
  • Published In

  • Neurosurgery  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lippitz BE; Halperin EC; Griffith OW; Colvin OM; Honore G; Ostertag CB; Bigner DD; Friedman HS; Guthrie BL; Shaw EG
  • Start Page

  • 255
  • End Page

  • 260
  • Volume

  • 26
  • Issue

  • 2