PHOTODYNAMIC THERAPY OF EARLY SQUAMOUS-CELL CARCINOMA WITH TETRA(M-HYDROXYPHENYL)CHLORIN - OPTIMAL DRUG-LIGHT INTERVAL

The optimal drug-light interval for effective photodynamic therapy (PD T) of early squamous cell carcinomas was evaluated with tetra(m-hydrox yphenyl)chlorin (mTHPC) by means of two complementary modalities: irra diation tests and ex vivo fluorescence microscopy. A Syrian hamster ch eek pouch tumour model was used in these experiments. Photodynamic the rapy on both tumour-bearing and contralateral healthy cheek pouch muco sae was performed at 650 nm and 514 nm. Light doses of 12 J cm(-2) wer e delivered at a light dose rate of 150 mW cm(-2) and light doses of 8 0 J cm(-2) were delivered at a light dose rate of 100 mW cm(-2) respec tively, al these two wavelengths, between 6 h and 12 days after the in jection of 0.5 mg kg(-1) body weight mTHPC. Two histologically differe nt types of tissue damage were observed: first, a non-selective and no n-specific ischaemic Vascular necrosis for the cases in which PDT took place during the first 48 h after the injection of the dye and, secon d, tissue-specific PDT damage, as a coagulation necrosis, when PDT too k place more than 72 h after injection of the dye. The time-dependent biodistribution of mTHPC investigated by fluorescence microscopy shows a weak and non-significant difference in relative fluorescence intens ities between early SCC and healthy mucosae. Up to 2 days after the in jection, the drug is mainly localized in the endothelial cells of the blood vessels. After this period, the dye accumulates in the squamous epithelia with a concentration peaking at 4 days. At all time points, a weak fluorescence intensity is observed in the underlying lamina pro pria and striated muscle. The information obtained from these studies could well be relevant to clinical trials as it suggests that time del ays between 4 and 8 days after i.v. injection should be optimal for PD T of early malignancies in hollow organs.