Photodynamic therapy using Photofrin in combination with buthionine sulfoximine (BSO) to treat 9L gliosarcoma in rat brain.

Abstract

The reactive oxygen mechanisms associated with cell damage after photodynamic therapy (PDT) may be exploited to enhance tumor destruction. Pharmacological reduction of glutathione (GSH), an inhibitor of reactive oxygen species, can be induced by administration of buthionine sulfoximine (BSO). BSO was administered in combination with Photofrin as the photosensitizer in order to promote PDT induced cell damage. Photofrin (12.5 mg/kg) or Photofrin with BSO (440 mg/kg) were administered to male Fischer rats (n = 27) containing an intracerebral 9L gliosarcoma or to non tumored rats. Brain tumor or non tumored brain was treated with an optical (632 nm) irradiance of 140 J/cm2. Animals were sacrificed 24 h after PDT and the volume of tissue necrosis was measured. Brain Photofrin concentration was measured in tumor and in non tumor bearing animals administered either Photofrin or Photofrin with BSO. GSH was measured by high pressure liquid chromatography in tumor and homologous non tumor tissue in animals administered BSO or control solution. The volume of tumor necrosis was significantly greater in animals administered Photofrin and BSO than in animals administered only Photofrin. No differences were detected in non tumored tissue damage between groups. No differences in Photofrin concentration were detected in tumored or nontumored animals between animals administered Photofrin and animals administered Photofrin and BSO. BSO administration preferentially and significantly reduced GSH in tumor compared to non tumor tissue. Our data suggest that BSO administration preferentially augments tumor destruction without compromising non tumored tissue.