PHOTODYNAMIC THERAPY ON THE NORMAL RABBIT LARYNX WITH PHTHALOCYANINE AND 5-AMINOLEVULINIC ACID-INDUCED PROTOPORPHYRIN-IX PHOTOSENSITIZATION

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 heal s by regeneration rather than scarring. As preservation of function is one of the main aims of treating laryngeal tumours, this project stud ied the effects of PDT on the normal rabbit larynx with two photosensi tisers, endogenous protoporphyrin IX (PPIX) induced by the administrat ion of 5-aminolaevulinic acid (ALA) and disulphonated aluminium phthal ocyanine (AlS(2)Pc). The main aims of the study were to examine the di stribution of protoporphyrin IX and AlS(2)Pc by fluorescence microscop y 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 t o the muscle. With 1 mg kg(-1) AlS(2)Pc, 1 h after administration, the drug was mainly in the submucosa and muscle, whereas after 24 h, it w as predominantly in the mucosa. PDT at 1 h caused deep necrosis wherea s 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 op timise the drug dose and time interval between drug and light to avoid unacceptable changes in normal areas.