DAMAGE TO TUMOR AND BRAIN BY INTERSTITIAL PHOTODYNAMIC THERAPY IN THE9L RAT-TUMOR MODEL COMPARING INTRAVENOUS AND INTRATUMORAL ADMINISTRATION OF THE PHOTOSENSITIZER

In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administr ation (intratumoural PDT) was studied. Twenty four rats received an in tratumoural injection of 4 or 40 mm(3) haematoporphyrin derivative (Hp D, 5 mg ml(-1)), followed by interstitial irradiation with 20 Joule (J ) (630 nm) 5 h later. For comparison, seven rats were treated with 20 Joule 24 h after an intravenous injection of 10 mg kg(-1) HpD (intrave nous PDT). With the chosen PDT parameters there was no important diffe rence between the damaged areas produced by intratumoural PDT or intra venous PDT. No selective tumour kill was observed. Even though normal brain tissue was heavily damaged, vital tumour parts were still presen t. Intravenous PDT caused extensive diffuse damage to small blood vess els in tumour and surrounding normal brain. Intratumoural PDT was char acterised by an infiltration of polymorphonuclear cells into damaged t issue, dilatation of larger blood vessels and gross haemorrhage. These results suggest an immediate vascular shutdown in the intravenous app roach, while in the intratumoural approach the vasculature remained pa tent initially. Because of the severe side effects observed, the use o f HpD seems not advisable for intratumoural PDT of brain tumours.