6533b827fe1ef96bd1286517

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Summary Background. Photodynamic therapy (PDT) has been under dis- cussion as additional treatment option for malignant gliomas. How- ever, damage not only to tumour tissue but also to normal brain has been demonstrated. The mechanisms of this unwanted side eect have not yet been clearly identified. Spreading of photosensitiser with oedema after disruption of the blood-brain-barrier and poten- tial sensitisation of normal tissue has been foundpreviously. The present study investigates the time- and dose-dependency of normal tissue damage to photodynamic therapy using Photofrin II9 after disruption of the blood-brain-barrier. Methods. Male wistar rats anaesthetisedwith chloral hydrate were subjectedto focal, cerebral coldlesions. Simultaneously, Photofrin II9 (PFII) was injected(2,5 or 5 mg/kg b.w.). Laser irrad iation (630 nm) was performedafter 4 h, 12 h and24 h with varying light doses. Control groups were subjected to focal cold lesion alone, cold lesion with laser irradiation, PFII followed by laser irradiation, or laser irradiation alone (n ¼ 6 all groups). 24 h later, brains were re- movedfor assessment of necrosis in coronal sections. Findings. Light dose had a significant impact on the extent of ne- crosis. Comparedto control animals (lesion only: 0.84 G 0.2 mm 2 ; lesion andirrad iation alone: 0.7 G 0.3 mm 2 ), the area of necrosis was increasedto 2.8 G 0.5 (50 J/cm 2 ), 3.5 G 1,1 (100 J/cm 2 ) and 4.3 G 0.7 mm 2 (200 J/cm 2 , 5 mg/kg b.w.; p < 0:01). This eect was time-dependent. Maximal necrosis (6.3 G 1,6 mm 2 ) was observed when brains were irradiated 12 h after PFII injection, with less ne- crosis occurring at 24 h (2.8 G 0.4 mm 2 ,p < 0:01). Reducing sen- sitiser dose to 2.5 mg/kg b.w. resulted in a reduction of necrosis (2.09 G 0.2 mm 2 ,p < 0:05Þ. Interpretations. Damage to oedematous tissue after photodynamic therapy using i.v. PFII and laser light at 630 nm depends on laser dose, sensitiser dose and the time point of laser irradiation. The time point of PDT shouldbe consid eredto prevent unwantedtissue re- actions. In the clinical setting however, defined damage to peri- tumoural tissue may be advantageous. This should be achievable by optimised timing and dosage of photodynamic therapy.