Short- and long-term normal tissue damage with photodynamic therapy in pigtrachea: a fluence-response pilot study comparing Photofrin and mTHPC

The damage to normal pig bronchial mucosa caused by photodynamic therapy (P DT) using mTHPC and Photofrin as photosensitizers was evaluated. An endobro nchial applicator was used to deliver the light with a linear diffuser and to measure the light fluence in situ. The applied fluences were varied, bas ed on existing clinical protocols. A fluence finding experiment with short- term (1-2 days) response as an end point showed considerable damage to the mucosa with the use of Photofrin (fluences 50-275 J cm(-2), drug dose 2 mg kg(-1)) with oedema and blood vessel damage as most important features. In the short-term mTHPC experiment the damage found was slight (fluences 12.5- 50 J cm(-2), drug dose 0.15 mg kg(-1)). For both sensitizers, atrophy and a cute inflammation of the epithelium and the submucosal glands was observed. The damage was confined to the mucosa and submucosa leaving the cartilage intact. A long-term response experiment showed that fluences of 50 J cm(-2) for mTHPC and 65 J cm(-2) for Photofrin-treated animals caused damage that recovered within 14 days, with sporadic slight fibrosis and occasional inf lammation of the submucosal glands. Limited data on the pharmacokinetics of mTHPC show that drug levels in the trachea are similar at 6 and 20 days po st injection, indicating a broad time window for treatment, The importance of in situ light dosimetry was stressed by the inter-animal variations in f luence rate for comparable illumination conditions.