1. To validate Optical Pharmacokinetics (OP) as a technique for rapid estimation of the tissue concentration of a well understood photosensitizing drug, aluminum disulphonated phthalocyanine (S2). This will compare OP measurements of the tissue concentration of S2 with the concentration measured by chemical extraction in 2 relatively homogeneous tissues, normal rat liver and muscle. It will also establish what volume of tissue is interrogated by an OP measurement. 2 To make OP measurements of the tissue concentration of S2 and other photosensitizers in a range of other less homogeneous normal tissues and transplanted cancers. This will compare OP with chemical extraction for a wider range of tissues, including cancers, to assess the potential for more general use of the technique. 3. To correlate OP measurements with the PDT effect of a fixed light dose. This study will establish in normal rat liver and colon whether the extent of PDT necrosis can be correlated with the OP measured level of photosensitizer when each animal is given the same drug dose with the same drug light interval and the same light dose. 4. To produce PDT necrosis of predictable and controllable extent. This is the ultimate challenge of the whole program - to match the extent of PDT necrosis to the extent of the disease process being treated in individual patients. In normal rat liver and colon, the light dose required to produce necrosis extending to a pre-defined point will be calculated on the basis of OP measurements. This dose will be delivered, measured either by a light sensor at the pre-defined limit of necrosis or by calculation based on the geometry of the light delivery system and the optical properties of the tissue. When the effects are sufficiently predictable in normal tissue, the study will be extended to transplantable cancers, prior to considering using the technique in phase I clinical studies.
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