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dc.contributor.advisorJurisson, Silvia S. (Silvia Sabine)eng
dc.contributor.advisorHennkens, Heather,eng
dc.contributor.authorRadford, Lauren L., 1987-eng
dc.date.issued2016eng
dc.date.submitted2016 Summereng
dc.descriptionAbstract from public.pdf file.eng
dc.descriptionDissertation supervisors: Drs. Silvia Jurisson and Heather Hennkens.eng
dc.descriptionIncludes vita.eng
dc.description.abstractTechnetium and rhenium have radioactive isotopes that are clinically useful for diagnostic (Tc-99m) or therapeutic (Re-186/188) purposes. This makes them attractive candidates for incorporation into pharmaceuticals. One way to incorporate radioactive metals into pharmaceuticals is through the use of a bifunctional chelating agent (BFCA), which inertly traps the metal while also attaching it to a targeting biomolecule. Technetium-99m is an attractive radionuclide not only because of its diagnostic capabilities, but also because it is a widely available and relatively affordable option. Two Tc-99m radiopharmaceuticals were created that seek to target somatostatin receptors (SSTRs), which are commonly overexpressed on neuroendocrine tumor tissues. Two different histidine-derived BFCAs were used to chelate a technetium-99m tricarbonyl core while simultaneously tethering it to an antagonist peptide with a high affinity for somatostatin receptor subtype two (SSTR2). Due to the fact that non-radioactive Re is in the same group as Tc, the analogous macroscale Re compounds were synthesized. This helped to determine the identity of the products made on the radiotracer level (nano- to picomolar) as well as determine receptor affinity through competitive binding assays in SSTR2-expressing cells. Both Re compounds, exhibited very good, low nanomolar affinities for SSTR2. The Tc-99m radiotracer products both exhibited high in vitro stability during challenges in cysteine, histidine, and mouse serum. Biodistribution and imaging studies in mice were also performed. The complexation of Re using a tetradentate diphosphinedithiol (DPDT) ligand was also explored. Rhenium is more readily oxidized than technetium, which can cause complications when seeking to use Re-186/188 radiopharmaceuticals in the body. Complexation with more reducing ligands (such as DPDT) may help stabilize Re(V) in the body. Thus, the initial chemistry of Re- and Tc-DPDT complexes was explored. This led to the creation of a highly stable Re(V)-DPDT complex, which remained stable in oxidative environments over a period of several months. Macroscale reactions using the DPDT ligand to synthesize the Tc-99 counterpart led to the formation of Tc(III) complexes from Tc(VII), without the need for additional reducing agents.eng
dc.description.bibrefIncludes bibliographical references (pages 105-118).eng
dc.format.extent1 online resource (xiv, 119 pages) : illustrationseng
dc.identifier.merlinb118910231eng
dc.identifier.oclc992170458eng
dc.identifier.urihttps://hdl.handle.net/10355/57255
dc.identifier.urihttps://doi.org/10.32469/10355/57255eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccesseng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.eng
dc.subject.FASTTechnetium -- Isotopeseng
dc.subject.FASTRhenium -- Isotopeseng
dc.subject.FASTChelation therapyeng
dc.subject.FASTRadiopharmaceuticals -- Researcheng
dc.titleTechnetium and rhenium (I and V) complexes for radiopharmaceutical applicationseng
dc.typeThesiseng
thesis.degree.disciplineChemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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