Photodynamic therapy for malignant mesothelioma: preclinical studies for optimization of treatment protocols.

Abstract Effective photodynamic therapy (PDT) depends on the optimization of factors such as drug dose, drug–light interval, fluence rate and total light dose (or fluence). In addition sufficient oxygen has to be present for the photochemical reaction to occur. Oxygen deficits may arise during PDT if the photochemical reaction consumes oxygen more rapidly than it can be replenished, and this could limit the efficacy of PDT. In this study we investigated the influence of the drug–light interval, illumination-fluence rate and total fluence on PDT efficacy for the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). The effect of increasing the oxygenation status of tumors during PDT was also investigated. PDT response was assessed from tumor-growth delay and from cures for human malignant mesothelioma xenografts grown in nude mice. Tumor-bearing mice were injected intravenously with 0.15 or 0.3 mg·kg−1 mTHPC, and after intervals of 24–120 h, the subcutaneous tumors were illuminated with laser light (652 ...