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dc.contributor.advisorSmith, Charles J. (Charles Jeffrey), 1969-eng
dc.contributor.authorRetzloff, Lauren Brooke, 1980-eng
dc.date.issued2009eng
dc.date.submitted2009 Falleng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on March 25, 2010).eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionThesis advisor: Charles J. Smith.eng
dc.description"December 2009"eng
dc.descriptionPh. D. University of Missouri-Columbia 2009.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- pharmacology.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Gastrin-releasing peptide (GRP) receptors are overexpressed on approximately two thirds (62-71%) of primary breast carcinomas and all (100%) of the corresponding metastatic sites. These receptors may be targeted with bombesin (BBN), a tetradecapeptide initially isolated from the skin of the fire bellied toad Bombina bombina, which binds to GRP receptors with both high affinity and specificity. These facts were exploited to develop a series of [superscript 99m]Tc-(CO)[subscrip 3]-X-Y-BBN(7-14)NH2 derivatives, where X = PZ1 or DPR and Y = [Beta]Ala, GGG, GSG, Peg5, Peg8, SGS, or SSS, whose ability to detect and diagnose breast cancer was analyzed. Among these conjugates, the 99mTc-(H[subscript 2]O) (CO)[subscript 3]-DPR-Y-BBN(7-14)NH2 analogs containing the amino acid spacer sequences GSG and SSS exhibited the highest levels of receptor-mediated accumulation and retention in the GRP receptor positive tissues of T47-D tumor-bearing SCID mice. Due to both their moderate residualization in tumor tissue and their rapid clearance from nontarget tissues, these derivatives demonstrated favorable tumor-to-background ratios, which allowed for the clear visualization of tumor tissue. This tumor tissue was clearly visible despite the presence of low levels of background radioactivity.eng
dc.format.extentxii, 221 pageseng
dc.identifier.oclc574727480eng
dc.identifier.urihttps://hdl.handle.net/10355/6740
dc.identifier.urihttps://doi.org/10.32469/10355/6740eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertations.eng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.subject.lcshBreast -- Tumors -- Radionuclide imagingeng
dc.subject.lcshBombesineng
dc.subject.lcshGastrin -- Metabolismeng
dc.subject.lcshPeptides -- Metabolismeng
dc.subject.lcshTechnetium compoundes -- Pharmacokineticseng
dc.subject.meshBreast Neoplasms -- radionuclide imagingeng
dc.subject.meshBombesin -- analogs & derivativeseng
dc.subject.meshGastrin-Releasing Peptide -- metabolismeng
dc.subject.meshBombesin -- pharmacokineticseng
dc.subject.meshBreast Neoplasms -- metabolismeng
dc.subject.meshOrganotechnetium Compounds -- pharmacokineticseng
dc.titleDesign, synthesis, and evaluation of radiolabeled bombesin conjugates for the diagnosis of breast cancereng
dc.typeThesiseng
thesis.degree.disciplinePharmacology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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