PHOTODYNAMIC THERAPY AND HYPEROXYGENATION

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Previous studies in this project have indicated that one of the critical parameters influencing tumor response to Photodynamic Therapy (PDT) is the level of oxygenation in the tumor during the treatment. Based upon this data we hypothesize that tumor response to PDT without a concomitant increase in normal tissue toxicity, can be improved by various hyperoxygenation techniques. We further hypothesize that the mechanism for this enhancement will increase direct cell killing in previous hypoxic regions of the tumor. Finally, we also hypothesize that the differences in improvement in response seen in the two transplant model systems to be employed will correlate with the theoretical models of oxygen diffusion in the two systems. The C3H mouse/MCA (mammary adenocarcinoma) tumor system implanted into either the leg or flank will be the two model systems employed for all studies. To test the hypotheses the following specific aims will be addressed. First we propose to demonstrate that intratumor oxygenation can be directly manipulated by subjecting the animals to various hyperoxygenation conditions. We then propose to demonstrate enhanced tumor response to PDT treatment for those treatment conditions showing improvement in oxygenation. Subsequently, for those sets of conditions, oxygen and treatment variables, showing improved tumor response, as in vitro/in vivo assay system will be employed to demonstrate that the enhancement of response is attributable to enhanced direct cell killing.