CORE--DRUG EVALUATION

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The overall aim of the Drug Evaluation Core is to provide support for routine procedures, assays and analyses required by the investigators of the Program Project. Generally, existing methodology will be used. New methods, or modifications of established methods, will be developed with the Projects and Cores as needed. Methods to be used by the Core include, but are not limited to, the following: (i) measurement of drug lipophilicity, using computer estimates, HPLC retention times and oil:buffer partitioning methods; (ii) determination of drug levels in cells, tissues and biological fluids using absorbance, fluorescence and extraction/dissolution methods. These methods will be performed for cultured cells, animal models, and patients in clinical trials; (iii) determination of photosensitizer concentrations using noninvasive in situ reflectance spectroscopy and fluorimetry. These measurements will be performed in animal models and patients in clinical trials; (iv) measurement of tumor response to PDT, including maintenance of electronic maintenance of electronic-caliper tumor measurement and computerized data storage systems; (v) measurement of vascular response to PDT using a fluorescein exclusion assay and specially constructed, non-invasive in situ fluorometer; (vi) measurement of normal tissue toxicity to PDT using the well established murine foot response model; (vii) measurement of cellular responses to PDT using in vitro and in vivo/ex vivo (excision assay) models; (viii)detection of photosensitizers and metabolites in cells, tissues and fluids using analytical HPLC. (ix) measurement of albumin binding of photosensitizers using high- performance displacement chromatography; (x) determine tissue and cellular sites of photosensitizer localization using confocal fluorescence microscopy; (xi) preparation of specimens for histology, histology method development. The activities of the Drug Evaluation Core will be essential for maximizing the yield of useful information from the integrated Projects and Cores in this Program Project. Core personnel will perform, direct or supervise these routine procedures, resulting in increased consistency as well as economy of scale; this consolidation will also improve quality control and will make it more feasible to exchange data between Projects.