Experimental studies to assess the potential of photodynamic therapy for the treatment of bronchial carcinomas.

摘要

BACKGROUND--Photodynamic therapy (PDT) is a technique for producing localised tissue necrosis with light after prior administration of a photosensitising drug. There is some selectivity of uptake of photosensitisers in malignant tissue, although this is difficult to exploit. Full thickness necrosis in normal and neoplastic colon heals without perforation because of a lack of effect on collagen, making local cure a possibility. The experiments described here aim to establish whether these conclusions are also valid for bronchial tumours. METHODS--In pharmacokinetic studies normal rats were given 5 mg/kg of the photosensitiser aluminium sulphonated phthalocyanine (A1SPc) intravenously and killed up to one month later. The distribution of A1SPc in the trachea was measured by chemical extraction and fluorescence microscopy. In subsequent experiments sensitised animals were treated with light delivered to the tracheal mucosa through a thin flexible fibre and the resultant lesions were studied for their size, mechanical strength, and healing. A series of resected human bronchial carcinomas were examined histologically for their collagen content. RESULTS--The tracheal concentration of A1SPc in normal rats was maximum 1-20 hours after administration. Fluorescence microscopy revealed that most was in the perichondrium and submucosal stroma, with little in the cartilage. Light exposure showed necrosis of the soft tissues which healed by regeneration, but no effect on cartilage and no reduction in the mechanical strength of the trachea at any stage. Histological examination of resected human bronchial carcinomas showed more collagen in the tumour areas than would be found in normal regions. CONCLUSIONS--PDT leads to necrosis of the soft tissues of the normal trachea but there is complete healing by regeneration, no risk of perforation (due to collagen preservation), and no effect on cartilage. Human bronchial carcinomas apparently contain more collagen than normal bronchi which may give protection against perforation following necrosis induced by PDT. PDT may have a role in eradicating small volumes of tumour tissue in situ and could be valuable for treating (1) small carcinomas in patients unfit for resection, (2) tumour remaining after surgical resection, (3) stump recurrences, or (4) to prolong palliation of tumours after debulking with the NdYAG laser.