PHTHALOCYANINE PHOTOSENSITIZERS FOR THE TREATMENT OF BRAIN-TUMORS

In vitro and in vivo studies were undertaken utilizing an established rat glioma cell line (C6) to compare the phototoxicity characteristics of aluminium tetrasulfonated phthalocyanine (AlSPc), zinc tetrasulfon ated phthalocyanine (ZnSPc) and haematoporphyrin derivative (HPD), AlS Pc and ZnSPc were inherently less cytotoxic in the dark compared to Hp D with 50% colony survival at 275, 355 and 14 mu g/ml respectively, An in vitro phototoxicity study at equimolar concentrations demonstrated a 50% reduction of colony survival after exposure to white light at 1 minute for HpD, 10 minutes for AlSPc and 12 minutes for ZnSPc, The pr esence of fetal bovine serum (FBS) in the medium resulted in reduced i n vitro uptake of AlSPc and increased cellular retention which was det ermined quantitatively by a fluorescence assay following extraction, T his assay was also used to determine the in vivo uptake of AlSPc, whic h was maximal in the intracerebral C6 glioma model at 6 hours (12.3 mu g/g tissue) post-intravenous administration of a 1 mg/kg dose of AlSP c, corresponding to a tumour:normal brain ratio of 22:1.