Photoradiation therapy (PRT) is a new modality for treatment of a variety of cancers through the combined use of systemically administered photosensitizing porphyrins and local application of light. The proposed program is intended to determine mechanisms of action of PRT and to improve the efficiency and selectivity of the treatment. Specifically this proposal entails studies in the following areas: 1. Continued drug development and evaluation will be carried out through x-ray crystallography, NMR spectroscopy, mass spectral analysis, measurements of singlet oxygen and fluorescent yields, structural modification, and cell and animal studies concerning therapeutic effect and pharmacokinetics. 2. Determination of the mechanism(s) of tumour destruction by PRT will be carried out through in vivo to in vitro cell survival assays, drug distribution studies, studies of vascular damage by PRT, in vitro studies of the effects of post-PRT-treatment conditions, and studies of possible effects of PRT on immunologic mechanisms. 3. The improvement of PRT through fractionation and the use of adjuvant modalities will be studied in in vitro and in vivo experiments including treatment combinations with hyperthermia and chemotherapeutic agents. 4. The continued development of methodology and equipment will include in vivo measurement of light flux and tissue porphyrin levels and the evaluation of a pulsed laser system for PRT.
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