The goal of the program is the systematic investigation of the therapy of experimental central nervous system (CNS) tumors including the pathogenesis and therapy of experimental metastatic CNS cancer. Three rat models of cancer metastatic to the CNS have been developed using the rat Walker 256 carcinosarcoma: brain tumor, meningeal carcinomatosis and epidural spinal cord compression. In addition, directly inoculated brain tumor models representing metastatic disease (Walker 256) and primary brain tumor (C6 glioma) have been developed. Using these models, problems of therapy in this disease not directly approachable in patients are being investigated using the indicated techniques: (1) Regional (50 x 50 x 20 Mum) changes in cerebral blood flow measured by 14C-iodoantipyrine (14C-IAP) uptake and quantitative autoradiography (QAR). (2) Regional changes in blood-brain barrier (BBB) and blood-tumor barrier (BTB) induced by CNS tumors and measured by 14C-alpha aminoisobutyric acid (14C-AIB) uptake using QAR. (3) Entry of radiolabeled-chemotherapeutic agents into CNS tumors as measured by QAR. (4) The mechanism of cerebral (and spinal cord) edema formation and its treatment by corticosteroid hormones as measured by 14C-AIB, 14C-ethylenediamine-tetra-acetic acid (14C-EDTA) and QAR. (5) The relationship of computed tomographic (CT) scanning, BBB and BTB breakdown and tumor growth. (6) Regional cerebral glucose metabolism in metastatic brain tumor and meningeal carcinomatosis measured by 14C-2-deoxy-glucose uptake and QAR. (7) Radiotherapy of metastatic CNS tumors and the effect of radiotherapy on entry of chemotherapeutic drugs. (8) CNS toxicity of chemotherapeutic agents.
