The objective of this proposal is to enhance the treatment of brain tumor with PDT. We have identified two methods to increase the efficacy of PDT to selectively kill brain tumor relative to normal brain. Photofrin administered encapsulated in a liposome and photofrin administered in conjunction with buthionine sulfoximide (BSO) (a glutathione inhibitor) significantly increases the PDT toxicity to tumor cells. In this project, we will develop, implement and optimize these con-PDT treatment methods of enhancing the PDT of brain tumor and investigate biophysical mechanisms responsible for this therapeutic enhancement.
Aim A: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin encapsulated in a liposome (Photofrin-liposome) as the photosensitizing agent compared to Photofrin in a dextrose vehicle (Photofrin-dextrose) as the photosensitizing agent. Hypothesis A: The enhancement of PDT in the treatment of brain tumor with Photofrin-liposome when compared to Photofrin-dextrose is attributed to alterations of the pharmacokinetics and the intracellular localization of Photofrin.
Aim B: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin by using buthionine sulfoximide (BSO) as an adjuvant to PDT. Hypothesis B: Administration of BSO decreases the level of gluthione in brain tumor tissue and therefore augments the intensity of brain tumor destruction with PDT. We expect that the optimization of these methods of enhancement of PDT destruction of brain tumor will find application in the clinic and may direct augmentation of human brain tumor treatment.
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