The objective of this research effort is the assessment, in vivo, and regionally of metabolic pathways in various organs, specifically the brain, the heart, and the lungs, by following the fate of radioactively-labeled metabolic substrates. The ultimate goals of this investigation are to develop and apply methods for the in vivo and regional measure of physiological processes and to extend this knowledge to the understanding of basic biological processes and to the understanding and diagnosis of pathology. The proposed approach consists of labeling selected metabolic substrates or other molecules of importance in physiological processes with a radioactive nuclide, the decay of which is accompanied by the generation of high energy electromagnetic radiation. After the systemic administration of the substrate to the subject under study, the location of the nuclide, as a function of time, is followed by externally placed detectors, or more often by positron emission tomography (PET), and the metabolic pathway studied is unraveled through the application of a suitable mathematical model. For this purpose, the labels are, with few exceptions, nuclides akin to those found in the chemical structure of living matter. We propose to use carbon-11, oxygen-15, and, in the labeling of drugs and substrate analogs, fluorine-18. These nuclides are prepared by cyclotrons located in our medical center. All of them decay with the emission of positrons, which, as they are absorbed, generate the annihilation radiation ;which is used in generating """"""""functional images"""""""". The program includes four areas: (1) chemical investigations; (2) neurological studies; (3) cardiovascular studies; and (4) pulmonary studies. The above projects which share the common core facilities and are extensively crosslinked by common goals, armamentarium, and methodology include the Departments of Radiology, Internal Medicine (Divisions of Cardiology and Pulmonary Medicine), Neurology and Neurosurgery, and Psychiatry.
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