CORE--PHOTOSENSITIZER EVALUATION

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One emphasis of this program project is to develop new phthalocyanine (Pc) photosensitizers (PS) with better antitumor properties for PDT. The purpose of the 'photosensitizer evaluation core' is to establish basic in vitro and in vivo data on the Pc PS synthesized in Project 1. For this purpose, the core will provide information generated in standardized analysis. Each newly synthesized PS will be assessed in parallel with Pc 4, and the photodynamic efficacy of the compound will be rated in the standardized test system as 'inferior', 'equal' or 'superior' to Pc 4. The results will be communicated to the program investigators. The choice for ranking of newly synthesized compounds in relation to Pc 4 is made because a) this was the lead compound among the first 10 synthesized, and b) other projects have considerable experience and preliminary data with this compound. This core will also generate more detailed information on selected promising PS. For this, the decision will be made by the investigators of Projects 1-3. The Director of this core Project is also a co-investigator of Project 3, and therefore will also participate in decisions, experimental designs, and data interpretation for these studies. The core will perform the following six functions: 1. We will determine the partitioning of newly synthesized PS between n-octanol vs. saline. 2. We will conduct initial in vitro evaluation of PS. 3. We will define initial PDT responses of PS. 4. We will determine distribution of PS in plasma, tumor and other tissues in vivo. 5. We will determine systemic toxicity and cutaneous photosensitivity responses of PS, and 6. We will study detailed PDT effects of selected PS. The priority for testing each PS will vary with the type of structure. This 'decision network' is described in the program narrative.