Photodynamic therapy with porphyrin and phthalocyanine sensitisation: Quantitative studies in normal rat liver

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Abstract
Selective sensitization of malignant tumours to monochromatic light (photodynamic therapy, PDT) is a promising approach to cancer treatment, but current sensitizers are unsatisfactory and the parameters controlling effects produced in normal and neoplastic tissue are poorly understood. To quantify the effects in a relatively homogeneous organ, we carried out experiments in the livers of normal rats following systemic sensitization with haematoporphyrin derivative (HpD) and a new sensitizer, a sulphonated aluminium phthalocyanine (A1SPc) using light from an Argon pumped tunable dye laser. Damage from PDT (dominant at 100 mW laser power) could be distinguished from that due to local hyperthermia (dominant at 400 mW). For both sensitizers, the extent of PDT necrosis increased with the applied light energy and was abolished by occluding the hepatic blood flow during therapy. With HpD, the extent of PDT necrosis was maximum with only a few hours between sensitization and therapy, and was not detectable when this interval was increased to a week. With A1SPc, the extent of necrosis in liver changed little with sensitization times from 1 h to 1000 h (6 weeks), and declined slowly thereafter, matching the amount of A1SPc measurable by alkali extraction, although prolonged photosensitization was not seen with A1SPc in muscle. Less cutaneous photosensitivity was seen with A1SPc than with HpD. A1SPc is easier to produce and handle than HpD, has a more appropriate strong absorption peak (at 675 mm) and from these results, warrants further study as a photosensitizer for PDT.