A series of monomeric
porphyrins (2-8) based on
porphyrin C (1) have been tested as sensitisers for
photodynamic therapy (
PDT) of cerebral
glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity,
phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (
porphyrin 7, molecular weight 863 Da and
porphyrin 8, molecular weight 889 Da), which had greater photoactivity than
porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of
porphyrins 7 and 8 was studied in the mouse C6
glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal
drug uptake levels in tumour occurred 9 and 6 h after
intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of
PDT using
porphyrin 7 activated by the
gold metal vapour
laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6
glioma. At a
drug dose of 10 mg
porphyrin 7 kg-1
body weight and
laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was 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
body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of
necrosis in normal brain.