Development of tricarbonyl Re and Tc-99m complexes for radiopharmaceutical and Hanford waste applications

Emily Witthuhn

doi:10.7273/000004134

99mTc has become the workhorse for radiopharmaceutical development due to its favorable half-life and radiation emission (t1/2 = 6.02 h, γ = 140 keV (89%)). Its simple production from 99Mo/99mTc generators grants it a benefit over other radiopharmaceutical isotopes. 99mTc provides effective diagnostic imaging of organs, metabolic pathways, and specific biological tissues with the use of Single Photon Emission Computed Tomography (SPECT). Additionally, the transition metal characteristics of 99mTc and a wide variety of oxidation states allows for structure manipulation for a variety of targeting probes. The development of fac-[99mTcI(CO)3(OH2)3]+ has allowed for facile incorporation of chelates and biomolecules to specifically target a tissue of interest within the body. These chelates vary in denticity and ligand donor atoms, and for specific cellular uptake, they are often developed in conjunction with a biomolecule for receptor-binding interactions. Another characteristic of these radioactive metal-containing compounds is the addition of fluorescent ligands to provide a second imaging technique contained in a single probe. Although 99mTc is optimal for radiopharmaceuticals, its long-lived daughter product (99Tc) produced from fission of 235U presents a challenge in environmental cleanup attempts and spent nuclear fuel reprocessing. While most often existing as the fully oxidized species (99TcVIIO4-), many non-pertechnetate species of lower oxidation states have been reported in Hanford waste tanks. The research discussed in this thesis includes two major projects: the first including the synthesis of a pyridine-imidazole ligand used as a bidentate aromatic amine-based ligand for chelation to fac-[99mTcI(CO)3(OH2)3]+. Used in conjunction with a phosphine based ligand (PPh3) in 2+1 and 2+1+1 strategies, full characterization was achieved along with complex stability, and cellular uptake. Luminescent data was obtained including fluorescence data and quantum yields revealing optimal characteristics for fluorescence imaging. The second research area investigates a variety of ligands and their chelation to fac-[99mTcI(CO)3(H2O)3]+ as a model non-pertechnetate species present in the strongly basic and high ionic strength of Hanford waste tanks. Ligands were selected based on their previous successes in nuclear medicine; their chelation efficiencies were determined in multiple environments including a simulation of Hanford waste tank 241-AN-106.

Development of tricarbonyl Re and Tc-99m complexes for radiopharmaceutical and Hanford waste applications

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