EVALUATION OF PORPHYRIN-C ANALOGS FOR PHOTODYNAMIC THERAPY OF CEREBRAL GLIOMA

A series of pure, monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cere bral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vitro screening, consisting of cytotoxicity, phototoxici ty (red light) and subcellular localisation studies, revealed two sens itisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecul ar weight 889 Da), which had greater photoactivity than porphyrin C an d similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellula r localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrin s 7 and 8 was studied in the mouse C6 glioma model as well as in biops y samples from normal brain, liver, spleen and blood. Maximal drug upt ake levels in tumour occurred 9 and 6 h after intraperitoneal injectio n for 7 and 8 respectively, at which time the tumour to normal brain r atios were 15:1 and 13:1 respectively. The effect of PDT using porphyr in 7 activated by the gold metal vapour laser tuned to 627.8 nm was st udied in Wistar rats bearing the intracerebral C6 glioma. At a drug do se of 10 mg porphyrin 7 kg(-1) body weight and laser doses of up to 40 0 J cm(-2) light, selective tumour kill with sparing of normal brain w as achieved, with a maximal depth of tumour kill of 1.77 +/- 0.40 mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg(-1) b ody weight resulted in a greater depth of tumour kill, but also signif icantly increased the likelihood and extent of necrosis in normal brai n.