title: Photodynamic therapy on the normal rabbit larynx with phthalocyanine and 5-aminolaevulinic acid induced protoporphyrin IX photosensitisation.
abstract: Photodynamic therapy (PDT) is a promising technique for the treatment of small tumours in organs where it is essential to minimise damage to immediately adjacent normal tissue as PDT damage to many tissues heals by regeneration rather than scarring. As preservation of function is one of the main aims of treating laryngeal tumours, this project studied the effects of PDT on the normal rabbit larynx with two photosensitisers, endogenous protoporphyrin IX (PPIX) induced by the administration of 5-aminolaevulinic acid (ALA) and disulphonated aluminium phthalocyanine (AIS2Pc). The main aims of the study were to examine the distribution of protoporphyrin IX and AIS2Pc by fluorescence microscopy in the different regions of the larnyx and to assess the nature and subsequent healing of PDT damage. Peak levels of PPIX were found 0.5-4 h after administration of ALA (depending on dose) with highest levels in the epithelium of the mucosa. With 100 mg kg-1, PDT necrosis was limited to the mucosa, whereas with 200 mg kg-1 necrosis extended to the muscle. With 1 mg kg-1 AIS2Pc, 1 h after administration, the drug was mainly in the submucosa and muscle, whereas after 24 h, it was predominantly in the mucosa. PDT at 1 h caused deep necrosis whereas at 24 h it was limited to the mucosa. All mucosal necrosis healed by regeneration whereas deeper effects left some fibrosis. No damage to cartilage was seen in any of the animals studied. The results of this study have shown that both photosensitisers are suitable for treating mucosal lesions of the larynx, but that for both it is important to optimise the drug dose and time interval between drug and light to avoid unacceptable changes in normal areas.
authors.affiliation: National Medical Laser Centre, University College London Medical School.
authors.forename: D
authors.initials: D
authors.lastname: Kleemann
authors.forename: A J
authors.initials: AJ
authors.lastname: MacRobert
authors.forename: T
authors.initials: T
authors.lastname: Mentzel
authors.forename: P M
authors.initials: PM
authors.lastname: Speight
authors.forename: S G
authors.initials: SG
authors.lastname: Bown
mesh_terms: D000622:Aminolevulinic Acid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007830:Larynx / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D009336:Necrosis; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011524:Protoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C060570:aluminum phthalocyanine; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX