The long term objective of our animal research is to provide important information necessary to improve the clinical application of intraarterial chemotherapy for treating brain tumors. More specifically, we will continue our current studies aimed at delineating the pharmacokinetic parameters associated with intraarterial administration of chemotherapeutic agents. Emphasis will be placed on evaluating how the intraarterial advantage (Rd) of drug delivery can be improved through (1) modifying the manner in which BCNU is dissolved for infusion; (2) using steroids and non steroid agents to reduce brain tumor edema and improve drug delivery, and; (3) using a short half-life experimental chemotherapeutic agent ideally suited for intraarterial delivery. Attention will also be given to evaluating the pharmacokinetics of IA and IV administered FUDR, which could theoretically have positive practical application as a drug to be used in combination with nitrosoureas in treating brain tumors. Experimental results will be compared to theoretical models of intraarterial drug delivery. In addition, physiological and morphologic parameters such as blood flow, brain tissue edema, and brain tumor ultrastructure will be measured and correlated with the pharmacokinetic measured parameters of drug delivery. This work is particularly important since very few quantitative studies of intraarterial chemotherapy for brain tumors have been reported. The incidence of human brain tumors is significant and the results of conventional forms of therapy are poor. Although intraarterial chemotherapy for brain tumors has provided some hope of improving patient prognosis, information regarding the basic pharmacokinetics of this approach is lacking. Such basic information is essential in order to optimize drug delivery parameters. This information is particularly important to the Interventional Radiology community which is directly involved in intraarterial chemotherapy of brain tumors.
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