Phthalocyanine photosensitizers for the treatment of brain tumours

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 tetrasulfonated phthalocyanine (ZnSPc) and haematoporphyrin derivative (HpD). AlSPc and ZnSPc were inherently less cytotoxic in the dark compared to HpD with 50% colony survival at 275, 355 and 14 μg/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 presence of fetal bovine serum (FBS) in the medium resulted in reduced in vitro uptake of AlSPc and increased cellular retention which was determined quantitatively by a fluorescence assay following extraction. This assay was also used to determine the in vivo uptake of AlSPc, which was maximal in the intracerebral C6 glioma model at 6 hours (12.3 μg/g tissue) post-intravenous administration of a 1 mg/kg dose of AlSPc, corresponding to a tumour: normal brain ratio of 22:1.