THE PHOTODYNAMIC RESPONSE OF 2 RODENT TUMOR-MODELS TO 4 ZINC(II)-SUBSTITUTED PHTHALOCYANINES

Four novel zinc (II)-substituted phthalocyanines, varying in charge an d hydrophobicity, were evaluated in vivo as new photosensitizers for p hotodynamic therapy. Two rat tumours with differing vascularity were u sed: a mammary carcinoma (LMC1) and a fibrosarcoma (LSBD1), with vascu lar components six times higher in the latter (10.8% +/- 1.5) than in the former (1.8% +/- 1.4). Each sensitizer was assessed for tumour res ponse relative to normal tissue damage, and optimum doses were selecte d for further study, ranging from 0.5 to 20 mg kg(-1). Interstitial il lumination of the rumours was carried out using a 200-mu m-core optica l fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm , depending on the sensitizer. Light doses of between 200 and 600 J we re delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depen ding on sensitizer and type of tumour, with the most potent photosensi tizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an in farct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cel l damage could not be ruled out.