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Threshold effects of PDT in the normal rat colon with ALA photosensitization

Early clinical results of PDT on colon tumors using up to 60 mg/kg ALA given orally (comparable to 30 mg/kg if given i.v.) with light doses of 50 J showed only superficial necrosis. We investigated whether this could be due to subthreshold tissue concentrations of Protoporphyrin IX (PP IX) or suboptimal light treatment schedules. Normal Wistar rats were sensitized with 25 - 400 mg/kg ALA given i.v. and irradiated with 100 mW red light at 630 nm (copper vapor pumped dye laser) 10 - 200 J delivered via a fiber placed touching the colon mucosa at laparotomy at the time of peak PP IX concentration (1 - 4 hours depending on the dose used). Animals were killed 3 days later and the diameter of mucosal necrosis measured. No lesion was seen with 25 mg/kg. Increasing the ALA dose from 50 - 400 mg/kg, the lowest light dose to produce a lesion of > 5 mm fell from 100 J to 25 J. If ALA doses for rats and humans are comparable (which is likely) these results suggest that the drug and light doses used clinically are close to the thresholds levels, so better clinical results may be achieved by increasing the value of one or both.