Professor, Missouri,Research interests involve several different, yet related, areas of radioinorganic chemistry. One area focuses on the utilization of gamma and beta emitting radiometals in the development of potential diagnostic and therapeutic radiopharmaceuticals. A second area addresses methods for the detection and separation of radiometals, in particular technetium-99, for minimization and safe storage of radioactive waste. A third area involves the use of radiotracers to understand plant and microbial biology. All research areas are multidisciplinary and therefore involve collaborations with other scientists within the department as well as in other departments, and at other institutions. The area of radiopharmaceutical chemistry involves radioisotope production methods, development of separation methods, syntheses of ligands and coordination complexes, radiochemical syntheses, biochemistry, biology and radiology. We are focusing on the development of high specific activity radionuclides for these applications, in particular, Tc-99m, Re-188, Rh-105, Au-199, Pm-149, Ho-166, Lu-177, Ga-68, In-111, and As-72/77. We are using combinatorial chemistry approaches as well as traditional chemistry approaches to design better targeting molecules for receptors on tumors. We have been interested in the development of the chemistry, radiochemistry and biochemistry of potential diagnostic and therapeutic radiopharmaceuticals whose mode of targeting uses small biological molecules (e.g., peptides, antibody fragments, etc.). The primary targets to date have been melanoma, breast cancer, prostate cancer and neuroendocrine cancers. We have developed new ligand systems for rhodium(III), gold(III), and various oxidations states of rhenium and technetium. The ligand systems developed include thioether, phosphine, amine, imine, Schiff base, and thiolate functionalities for coordination to the various metals. Our emphasis is on developing metal complexes that are kinetically inert under physiological conditions. Our studies include the development of targets (accelerator and reactor), target-product separations (e.g., Re-186, As-72, As-77), the synthesis of new ligand systems (generally tetradentate), the synthesis of the transition metal complexes, the synthesis of the radiotracer analogs of these complexes, the determination of the stability of these complexes under physiological conditions, the determination of the binding of the various complexes to the appropriate receptors (in vitro), and the determination of the in vivo behavior of these complexes in both normal and tumor model mice. We are also interested in the similarities and differences in the chemistry of analogous Tc and Re compounds, such as the rates of formation and substitution, the mechanisms of formation, and their electrochemical behavior. These studies are important to the development of potential therapeutic radiopharmaceuticals based on Re. The area of radioenvironmental chemistry involves radiochemistry, inorganic chemistry and analytical chemistry. Technetium-99 is a long-lived radionuclide produced in about 6% yield from the fission of U-235 and Pu-239 used as fuel in nuclear reactors and weapons. Thus, it is a large component of the waste generated from the nuclear weapons era and from nuclear fuel reprocessing. The combination of its long half-life (212,000 years) and its mobility in the environment as the oxoanion pertechnetate makes Tc-99 a problem for long term storage and environmental migration. We have investigated the use of supramolecular hosts and phosphinimines to selectively bind pertechnetate, and sulfide reduction in the presence of mineral phases to investigate the immobilization of Tc-99. The area of radiotracers in plant biology involves the use of radiolabeled molecules (e.g., F-18-fluorosucrose, S-35-glutathione, Fe-59, Cd-111) to probe mechanistic processes in plants such as transport or signaling, and to investigate potential phytoremediation.

Inorganic and Radiopharmaceutical Chemistry including targetry, separations and radiotracer syntheses, Technetium Clathrochelates, Radiotracers in Plant Biology