Photodynamic therapy with porphyrin and phthalocyanine sensitisation: quantitative studies in normal rat liver.
Selective sensitisation of malignant tumours to monochromatic light (photodynamic therapy, PDT) is a promising approach to cancer treatment, but current sensitisers 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 sensitisation with haematoporphyrin derivative (HpD) and a new sensitiser, a sulphonated aluminium phthalocyanine (AlSPc) 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 sensitisers, 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 sensitisation and therapy, and was not detectable when this interval was increased to a week. With AlSPc, the extent of necrosis in liver changed little with sensitisation times from 1 h to 1000 h (6 weeks), and declined slowly thereafter, matching the amount of AlSPc measurable by alkali extraction, although prolonged photosensitisation was not seen with AlSPc in muscle. Less cutaneous photosensitivity was seen with AlSPc than with HpD. AlSPc is easier to produce and handle than HpD, has a more appropriate strong absorption peak (at 675 nm) and from these results, warrants further study as a photosensitiser for PDT.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D009132:Muscles / Q000378:metabolism; D009336:Necrosis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017324:Hematoporphyrin Derivative