MALONDIALDEHYDE DOSIMETRY IN LASER-IRRADIATED TISSUES SENSITIZED BY HEMATOPORPHYRIN DERIVATIVE

Photodynamic therapy (PDT) is based on the selective retention of a ph otosensitizer (hematoporphyrin derivative [HPD]) by tumor tissue and t he subsequent irradiation of this tissue with light. Unsaturated phosp holipids are important targets of membrane photodamage, and malondiald ehyde (MDA), an ultimate marker of lipid peroxidation, can easily be m easured by the fluorometric thiobarbituric acid (TBA) assay. To determ ine whether MDA content represents a reference for PDT intensity, tiss ue content in 7-week-old male nude mice was studied on biopsy samples after PDT (5 mg/kg HPD injected intravenously 24 hr before irradiation at 632 nm) with or without intraperitoneal injection of WR-2721 40 mi n before treatment. The FeCl3 method requiring only 15 min of incubati on in a 95 degrees C waterbath proved most effective compared with the method involving phosphotungstic acid or the MDA-TBA determination us ing a commercially available kit. Whatever the method used, the best r esults were found using a 60-min interval between treatment and freezi ng. MDA concentration in HPD-PDT-treated samples was significantly hig her than in HPD-tested controls (P <.01) and increased at laser irradi ation doses ranging from 0 to 50 J/cm(2). Administration of WR-2721 in traperitoneally significantly reduced MDA concentration (from 70% to 3 8%). A maximal effect was obtained with 100 mg/kg for brain (-70%) and 200 mg/kg for muscle (-47%). Higher doses produced no additional chan ges. The MDA assay is a simple tool for indirect evaluation of PDT, an d WR-2721 can decrease MDA content in normal tissue, suggesting the po ssibility of good protection for normal tissue during PDT.