The ``IQNP`` agent is an antagonist for the cholinergic-muscarinic receptor. Since the IQNP molecule has two asymmetric centers and either cis or trans isomerism of the vinyl iodide, there are eight possible isomeric combinations. In this report, the systematic synthesis, purification and animal testing of several isomers of radioiodinated ``IQNP`` are reported. A dramatic and unexpected relation between the absolute configuration at the two asymmetric centers and the stereochemistry of the vinyl iodide on receptor specificity was observed. The E-(R)(R) isomer shows specific and significant localization (per cent dose/gram at 6 hours) in receptor-rich cerebral structures (i.e. Cortex = 1.38 + 0.31; Striatum = 1.22 + 0.20) and low uptake in tissues rich in the M{sub 2} subtype (Heart = 0.10; Cerebellum = 0.04). In contrast, the E-(R)(S) isomer shows very low receptor-specific uptake (Cortex = 0.04; Striatum = 0.02), demonstrating the importance of absolute configuration at the acetate center. An unexpected and important observation is that the stereochemistry of the vinyl iodine appears to affect receptor subtype specificity, since the Z-(R,S)(R) isomer shows much higher uptake in the heart (0.56 + 0.12) and cerebellum (0.17 + 0.04). Studies are now in progress to confirm these exciting results in vitro. Progress has also continued during this period with several collaborative programs. The first large-scale clinical tungsten-188/rhenium-188 generator prototype (500 mCi) was fabricated and supplied to the Center for Molecular Medicine and Immunology (CMMI), in Newark, New Jersey, for Phase I clinical trials of rhenium-188-labeled anti CEA antibodies for patient treatment. Collaborative studies are also continuing in conjunction with the Nuclear Medicine Department at the University of Massachusetts where a generator is in use to compare the biological properties of {open_quotes}direct{close_quotes} and {open_quotes}indirect{close_quotes} labeled antibodies.

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.

In this report the use of a simple colorimetric assay employing the bisthiosemicarbazone (TSC) derivative of phenylglyoxal to evaluate the specific activity of spallation-produced copper-67 (Cu-67) samples is described. Four samples from the Los Alamos National Laboratory (LANL) and one sample from the Brookhaven National Laboratory (BNL) were analyzed and the results compared in a blind study'' with specific activity values obtained by isotope coupling plasma (ICP) analysis at the production sites. A good comparison was found, and these results indicate that the TSC approach is a simple, inexpensive, and rapid technique to determine the specific activity of spallation-produced Cu-67. The synthesis, radioiodination, and evaluation of deiodination in rats in vivo of two new maleimide agents for antibody labeling is also described. 3 figs., 1 tab.