title: Distribution and photodynamic effect of disulphonated aluminium phthalocyanine in the pancreas and adjacent tissues in the Syrian golden hamster.
abstract: Necrosis of small volumes of tumour tissue with photodynamic therapy (PDT) can be achieved relatively easily. For this to be clinically relevant, it is essential to know what the same treatment parameters do to adjacent normal tissues into which the tumour has spread. For pancreatic cancers, local spread to vital structures is common. We have studied chemical extraction, microscopic fluorescence kinetics and photodynamic effects of disulphonated aluminum phthalocyanine (AlS2Pc) in normal pancreas and adjacent tissues in hamsters. Chemical extraction exhibited a peak duodenal concentration of AlS2Pc 48 h after sensitisation, with levels much higher than in stomach and pancreas. With microscopic fluorescence photometry highest levels were seen in duodenal submucosa and bile duct walls 48 h after photosensitisation. Pancreatic ducts, duodenal mucosa and gastric mucosa and submucosa exhibited intermediate fluorescence with relatively weak fluorescence in pancreatic acinar tissue and the muscle layer of the stomach. As expected, on the basis of fluorescence intensity and chemical extraction studies, the duodenal and bile duct wall were the most vulnerable tissues to photodynamic therapy. When the dose of 5 mumol kg-1 of sensitiser was used, duodenal perforations, gastric ulcers and transudation of bile from the bile duct occurred. However, the lesions in the stomach and bile duct healed without perforation or obstruction, so only the duodenum was at risk of serious, irreversible damage. Using a lower dose of photosensitiser markedly reduced damage.
authors.affiliation: Department of Surgery, Rayne Institute, University College London, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Nuutinen
authors.forename: P T
authors.initials: PT
authors.lastname: Chatlani
authors.forename: J
authors.initials: J
authors.lastname: Bedwell
authors.forename: A J
authors.initials: AJ
authors.lastname: MacRobert
authors.forename: D
authors.initials: D
authors.lastname: Phillips
authors.forename: S G
authors.initials: SG
authors.lastname: Bown
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D006224:Cricetinae; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007211:Indoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents; D014018:Tissue Distribution
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C064331:aluminum phthalocyanine disulfonate