Optimization of photodynamic therapy with chlorins for chest malignancies

Photodynamic therapy (PDT) following surgical tumor resection is leading to improved local tumor control and might be useful for selected intrathoracic malignancies. However, optimal tumor selectivity of PDT is mandatory to avoid injury of adjacent normal tissues. (1) PDT was applied on human tumor xenografts (malignant mesothelioma, squamous cell carcinoma of the neck, adenocarcinoma of the colon). M-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derived mTHPC (MD-mTHPC) were administered i.p. The tumor and normal tissue of the hind leg were irradiated with 652 nm laser-light. Drug and light doses and drug-light intervals were varied. The extent of necrosis was assessed histologically. (2) Intrathoracic PDT was performed in minipigs with drug-light doses optimized in nude mice. After administration of the sensitizers i.v., intrathoracic structures were irradiated and analyzed histologically. The tumor selectivity of PDT increased in the xenograft model by: (1) choosing an appropriate drug light interval; (2) decreasing the drug dose while increasing the light dose; and (3) applying MD-mTHPC instead of mTHPC. In the minipig model, the extent of injury of intrathoracic structures was equally related to modulation of treatment conditions. The modification of chlorins and the modulation of the drug-light conditions improved the tissue selectivity of PDT. Nevertheless, further methodological optimizations are prerequisites for clinical use of PDT, especially for intraoperative application in thoracic surgery.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.