In this report the first fabrication and evaluation of an activated carbon-based osmium-194/iridium-194 generator system is described. Iridium-194 (t{sub {1/2}} = 19.2 h) decays by {Beta}{sup {minus}} emission (E{sub max} = 2.24 MeV) and is a potential candidate for radioimmunotherapy. An important characteristic is availability of {sup 194}Ir from decay of reactor-produced {sup 194}Os (t{sub {1/2}} = 6 y). A novel gas thermochromatographic method was developed for the one step conversion of metallic Os to OsO{sub 4} and subsequent separation and purification of OsO{sub 4}, which was then converted to the K{sub 2}OsCl{sub 6} for generator loading. The yield and the elution profile of carrier-free {sup 194}Ir, and {sup 194}Os breakthrough were determined for a prototype generator which was evaluated over a 10 month-period.l During this period several agents were also supplied to Medical Cooperative investigators, including iodine-123-labelled and iodine-125-labelled fatty acid analogues for studies at the Brookhaven National Laboratory. In addition, gold-198 and tungsten-188/-rhenium-188 generators were shipped to various investigators for therapeutic studies involving tumor-specific antibodies. 19 refs., 3 figs.

An evaluation of the Oak Ridge National Laboratory (ORNL) alumina-based tungsten-188/rhenium-188 (W-188/Re-188) generator system has continued. Our goal is to develop a prototype system which will provide sufficient levels of Re-188 for radiolabeling of tumor-specific antibodies for radioimmunotherapy. During this review period several samples were supplied for collaborative studies. Samples of rhenium-188 from the ORNL W-188/Re-188 generators were supplied to the National Institutes of Standards and Technology (NIST) as a calibration standard. Iodine-125-labeled IMP protein labeling agent was supplied to the University of Michigan for antibody radiolabeling studies (D. Buchsbaum, Ph.D.). The iodine-123-labeled BMIPP fatty acid analogue developed at ORNL was also supplied to collaborators at BNL for SPECT imaging studies of the effects of cocaine intoxication on myocardial fatty acid uptake in a canine model. Iodine-125-BMIPP was also supplied to the University of Bonn, Germany for continuing metabolic studies in an isolated heart model. In this report the resumption of radioisotope production in the HFIR following the restart of this important facility in July 1990 and the preparation and review and evaluation of issues for the DOE Tiger Team visit to ORNL on November 1--December 7 are also discussed. 2 figs., 1 tab.

During this period the properties of the unknown metabolite released from Langendorff-perfused rat hearts administered radioiodinated 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) have been further evaluated. Identification of this metabolite is important to provide a better understanding of the myocardial metabolism of methyl-branched fatty acids and to illuminate the factors affecting myocardial retention of such agents. The metabolite is the principal component in the outflow of the isolated rat hearts. Following isolation and purification of the metabolite, treatment with NaBH/sub 4/ had no effect on the chromatographic properties. In contrast, a much less polar product was formed by treatment with acetic anhydride, suggesting the presence of a primary or secondary hydroxyl group. In addition, the metabolite is soluble in dilute base and extracted from an acid solution with ether, demonstrating the presence of a carboxyl group. These combined results suggest BMIPP is metabolized to a hydroxy acid of unknown structure. Studies are now in progress to identify this material. Studies of the effects of chain length on the complexation of a series of p-carboxyalkylphenylglyoxal bis-(N-alkylthiosemicarbazones) (TSC) have continued. After complexation with either Cu-64 or Cu-67 followed by activation to the tetrafluorophenyl esters, the bifunctional ligands were attached to BSA and purified by G-25 Sephadex. Yields varied from 2--3% to 40%, with higher yields for the shorter chain analogues. Because of simpler formation and higher yield, future studies will focus on the radiolabeling of antibodies with the short-chain analogues of the 1,2-diketone TSC derivatives. Also during this period (I-131)IPPA was supplied to collaborators at the Institute of Clinical and Experimental Nuclear Medicine in Bonn, West Germany, for studies with an isolated working rat heart model.