A proposal is presented to utilize tracers labeled with positron emitters and positron emission transaxial tomographs (PETT) to carry out mapping of static and dynamic functions of the brain. An immediate application will involve the use of 18F-2-deoxy-2-fluoro-D-glucose (FDG) for measuring regional glucose metabolism in a variety of normal and pathological states in the baboon and human brain. In addition, this technique, pioneered by the University of Pennsylvania in collaboration with BNL, will be applied to determining sites of action in the brain related to specific drug intervention. A new aspect of the application of this combination of research tools will be to develop useful labeled agonists and antagonists and other psychotropic agents and apply them to basic studies on opiate, dopaminergic, and other receptor action. Thus, for the first time it may be possible to probe ligand-receptor interrelations in the intact brain in a non-invasive and quantitative way. Other applications will involve studies in anesthesia, enzyme mapping, and on the functional architecture of the human visual cortex. Studies to determine the relation between glucose metabolism and pathological state involve both the investigaion of fundamental relationships and also effectiveness of treatment as mirrored in metabolic activity. Twelve studies are proposed ranging from those on animals alone to research with human subjects involving both basic and clinical aspects. The clinical studies include the development of heretofore inaccessible information on aging, schizophrenia, and the relation of drug therapy to these states. Other clinical studies will use these techniques to study rCGM and rCBF before and after drug or surgical intervention, in treating patients with patent disease with the goal of improving diagnosis and therapy. The majority of these studies require as an essential aspect the improved spatial resolution of the newer PETT machines in order to be effective. Thus, the proposal includes a request for such a machine plus a request for modest cyclotron improvement in order to afford efficient realization of this project.
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