This program has two interrelated objectives. The first is to validate and extend current quantitative autoradiographic methods (QAR) for measurement of blood flow, vascular permeability, and regional glucose metabolism to brain tumors and irradiate brain. The second objective is to develop a detailed understanding of the time course of the irradiation response of brain tumor, (and where possible, normal brain) with respect to blood flow, permeability, and glucose metabolism. The research plan consists of five main experiments to be performed on normal rat brain and intracerebrally-transplanted rat malignant astrocytic gliomas under conditions of treatment with fractionated and unfractionated Cs-137 gamma irradiation. Blood flow will be examined by means of radiolabelled microsphere methods and QAR with the tracer, C-14 iodoantipyrine. Capillary permeability measurements will use QAR with C-14 Alpha-aminoisobutyric acid. Assessment of regional glucose metabolism will be based on current kinetic models which use C-14 deoxyglucose. A principal part of this work will be (a) to validate and refine some of the current QAR methods for measuring blood flow, permeability, and glucose metabolism, and (b) to explore new mathematical models that may more accurately portray these facets of brain tumor biology. This study will provide pathophysiologic information about brain tumor radiation response which will be useful in planning other treatment interventions, such as the timing of adjunctive chemotherapy, and treatment with radioprotectors, or radiosensitizers. Also, this project will serve as a scientific basis for the transfer of QAR-based measurement techniques from laboratory animals with brain tumors to human patients with malignant brain tumors studied with positron emission tomography.
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