title: Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid.
abstract: OBJECTIVE
  Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain.
  
  
  METHODS
  Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight). Tumors were induced by cortical inoculation of C6 cells and 9 days later, magnetic resonance (MR) images were obtained. On Day 10, animals were given 5-ALA (100 mg/kg body weight) and their brains were irradiated (100 J/cm2) 3 or 6 hours later. Seventy-two hours after irradiation, the brains were removed for histological examination. Irradiation of brains after administration of 5-ALA resulted in superficial cortical damage, the effects of which were not different from those of the irradiation alone. Induction of cold injury in combination with 5-ALA and irradiation slightly increased the depth of damage. In the group that received irradiation after intravenous administration of Photofrin II the depth of damage inflicted was significantly greater. The extent of damage in response to 5-ALA and irradiation in brains harboring C6 tumors corresponded to the extent of tumor determined from pretreatment MR images.
  
  
  CONCLUSIONS
  Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.
authors.affiliation: Department of Neurosurgery, Institute for Neuroradiology, Laser Research Laboratory, Institute for Neuropathology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Olzowy
authors.forename: Cornelia S
authors.initials: CS
authors.lastname: Hundt
authors.forename: Susanne
authors.initials: S
authors.lastname: Stocker
authors.forename: Karl
authors.initials: K
authors.lastname: Bise
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Reulen
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010789:Phototherapy; D011166:Porphyrins; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid; D017323:Dihematoporphyrin Ether