title: Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model.
abstract: OBJECTIVE
  Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of resection, indicating that a more aggressive local therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment involving the administration of a tumor-localizing photosensitizing drug, in this case aminolevulinic acid (ALA). The effect depends on the total light energy delivered to the target tissue, but may also be influenced by the rate of light delivery.
  
  
  METHODS
  In vitro experiments showed that the sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended on the rate of light delivery (fluence rate). The BT4C tumors were established intracranially in BD-IX rats. Microfluorometry of frozen tissue sections showed that photosensitization is produced with better than 200:1 tumor/normal tissue selectivity after ALA injection. Four hours after intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was delivered interstitially over 15 (high fluence rate) or 90 (low fluence rate) minutes. Histological examination of animals treated 14 days after tumor induction demonstrated extensive tumor necrosis after low-fluence-rate PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil infiltration in tumor tissue was increased by PDT, but was similar for both treatment regimens. Low-fluence-rate PDT administered 9 days after tumor induction resulted in statistically significant prolongation of survival for treated rats compared with nontreated control animals.
  
  
  CONCLUSIONS
  Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the survival for tumor-bearing animals.
authors.affiliation: Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo, Norway. evenag@labmed.uio.no
authors.forename: Even
authors.initials: E
authors.lastname: Angell-Petersen
authors.forename: Signe
authors.initials: S
authors.lastname: Spetalen
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Madsen
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Sun
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Carper
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Henry
authors.initials: H
authors.lastname: Hirschberg
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy*; D008027:Light; D009336:Necrosis; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D016019:Survival Analysis
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid