Photodynamic therapy for malignant mesothelioma: Preclinical studies for optimization of treatment protocols

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 photo chemical reaction to occur. Oxygen deficits may arise during PDT if the pho tochemical reaction consumes oxygen more rapidly than it can be replenished , and this could limit the efficacy of PDT, In this study we investigated t he influence of the drug-light interval, illumination-fluence rate and tota l fluence on PDT efficacy for the photosensitizer meta-tetrahydroxyphenylch lorin (mTHPC). The effect of increasing the oxygenation status of tumors du ring 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 w ere illuminated with laser light (652 nm) at fluence rates of 20, 100 or 20 0 mW.cm(-2). Tumor response was strongly dependent on the drug-light interv al. Illumination at 24 h after photosensitization was always significantly more effective than illumination at 72 or 120 h, For a drug-light interval of 24 h the tumor response increased with total fluence, but for longer dru g-light intervals even high total fluences failed to produce a significant delay in tumor regrowth, No fluence-rate dependence of PDT response was dem onstrated in these studies. Nicotinamide injection and carbogen breathing s ignificantly increased tumor oxygenation and increased the turner response for PDT schedules with illumination at 24 h after photosensitizer injection .