The animal research outlined in this proposal is directed towards extending clinical Diagnostic Radiology imaging (Computer Axial Tomography-CT and Nuclear Magnetic Resonance-NMR) and Interventional Radiology (arterial infusion chemotherapy) to improve the treatment of brain tumors. More specifically, work outlined in this proposal is intended to use a new animal brain tumor model to quantitatively compare how the intraarterial (IA) and intravenous (IV) administration of the chemotherapeutic agent BCNU affects animal tumor and non-tumor tissue drug distribution and tumor response (volume changes and animal survival times). The results will be compared to those predicted by theoretical drug modeling systems. In addition, systemic toxicity, relative to the route and dose of drug administration will be monitored and compared. The research will also investigate the effects of steroids and perfluorocarbons when used in combination with IA and IV chemotherapy. The effects of each of these combined with chemotherapy treatments on drug distribution in brain tumor and non-tumor tissue and tumor response will be studied. Diagnostic x-ray, CT and NMR imaging will be employed to help evaluate the effects of steroids on reducing edema associated with the tumor. This research is of particular importance since the incidence of human brain tumors is significant and the results of conventional forms of therapy are poor. The work proposed in this application should provide important information that is currently lacking and which should improve knowledge regarding the role of Interventional Radiology in brain tumor therapy. Results of the study should help to develop new forms of therapy to improve the care and management of the brain tumor patient.
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