This research involves the development and application of radiochemical generator to produce 122I (t1/2 3.6 min) from 122Xe (t1/2 20.1 h). The 122Xe radionuclide is obtainable as a waste by-product from the routine production of high purity 123I via the (p,5n) nuclear reaction; this will make the generator widely available at a relatively low cost. The half-life of the 122Xe parent is long enough to permit shipment of the generator throughout the United States, obviating the need of an on-site cyclotron to produce short-lived positron emitting radiopharmaceuticals such as 150-water and 150-CO for positron emission tomography (PET) investigations. The use of this generator with 18F-fluorodeoxyglucose for metabolic determinations and 18F-labeled ligand-receptor radiopharmaceuticals for receptor quantitation studies shipped from regional cyclotron facilities could result in greater application of PET in clinical settings for diagnostic imaging. 122I will give a low radiation dose per study and permit repeat studies at short intervals (20-30 min) in the same subject. The 122I radionuclide will be incorporated into a variety of amphetamine derivatives and the usefulness of these compounds evaluated as potential regional cerebral blood flow (rCBF) agents for PET. Validation of these agents will be carried out by utilizing animal distribution studies, measuring first-pass cerebral extraction, determining the rate of efflux of the tracer from the brain, assessing the rate of metabolic breakdown, and comparing flow values made with 122I-labeled compounds to rCBF measurements made with microsphere standards. Studies will be undertaken to evaluate 122I-labled serum albumin as a regional cerebral blood volume (rCBV) agent. Regional plasma CBV measurements will be made in normal and ischemic cat brains. 122I-iodoalbumin used with the 122I-labeled flow agents will permit combined rCBV and rCBF measurements in the same subject at closely spaced intervals.
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