{"id":{"repo_id":"missouri","oai_identifier":"oai:mospace.umsystem.edu:10355/7019"},"canonical_url":"https://search.dev.ndltd.org/etd/missouri/oai:mospace.umsystem.edu:10355/7019","repository":{"repo_id":"missouri","name":"University of Missouri","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Structure-activity relationship of octreotide analogues labeled with rhenium and technetium-99m","abstract":"The goal of this research is to cyclize octreotide analogues with ⁹⁹[supersript-m]Tc and ¹⁸⁶/¹⁸⁸Re radiometals to be used as diagnostic and therapeutic agents for neuroendocrine tumors, respectively. Several series of octreotide analogues that differ in their sequences, and/or coordination systems (S₂N₂ and S₃N) were developed. Their in vitro receptor binding affinity toward somatostatin receptors was measured via IC₅₀ studies. In vitro stability studies were carried out under physiological conditions on ⁹⁹[superscript-m]Tc-cyclized analogues in phosphate buffered saline, mouse serum, and under high cysteine concentration. The only analogue that expressed high receptor binding affinity was not stable at the tracer level; however, the other analogues were stable at the tracer level but at the expense of their receptor affinity. The effect of metal-cyclization on Tyr³-octreotate's receptor binding site was determined via three-dimensional molecular structure calculation, using two-dimensional NMR experiments as experimental constraints. From the obtained structures, it was concluded that the metal-cyclized Tyr³-octreotate's receptor binding site configuration was, to some extent, similar to that of the usually disulfide-cyclized counterpart.","abstract_html":"The goal of this research is to cyclize octreotide analogues with ⁹⁹[supersript-m]Tc and ¹⁸⁶/¹⁸⁸Re radiometals to be used as diagnostic and therapeutic agents for neuroendocrine tumors, respectively. Several series of octreotide analogues that differ in their sequences, and/or coordination systems (S₂N₂ and S₃N) were developed. Their in vitro receptor binding affinity toward somatostatin receptors was measured via IC₅₀ studies. In vitro stability studies were carried out under physiological conditions on ⁹⁹[superscript-m]Tc-cyclized analogues in phosphate buffered saline, mouse serum, and under high cysteine concentration. The only analogue that expressed high receptor binding affinity was not stable at the tracer level; however, the other analogues were stable at the tracer level but at the expense of their receptor affinity. The effect of metal-cyclization on Tyr³-octreotate's receptor binding site was determined via three-dimensional molecular structure calculation, using two-dimensional NMR experiments as experimental constraints. From the obtained structures, it was concluded that the metal-cyclized Tyr³-octreotate's receptor binding site configuration was, to some extent, similar to that of the usually disulfide-cyclized counterpart.","abstract_has_math":false,"creators":["Dannoon, Shorouk, 1982-"],"institution":"University of Missouri--Columbia","degree_name":"Ph. D.","degree_level":"Doctoral","degree_discipline":"Chemistry (MU)","degree_department":null,"school":null,"contributors":[],"advisors":["Lewis, Michael R.","Jurisson, Silvia S. (Silvia Sabine)"],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-24T03:07:24Z","subjects":[],"languages":["eng","English"],"rights":["OpenAccess."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/7019"],"render_values":[{"text":"https://doi.org/10.32469/10355/7019","href":"https://doi.org/10.32469/10355/7019","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10355/7019","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Lewis, Michael R.","Jurisson, Silvia S. 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The only analogue that expressed high receptor binding affinity was not stable at the tracer level; however, the other analogues were stable at the tracer level but at the expense of their receptor affinity. The effect of metal-cyclization on Tyr³-octreotate's receptor binding site was determined via three-dimensional molecular structure calculation, using two-dimensional NMR experiments as experimental constraints. From the obtained structures, it was concluded that the metal-cyclized Tyr³-octreotate's receptor binding site configuration was, to some extent, similar to that of the usually disulfide-cyclized counterpart."]},{"key":"dc:title","label":"Title","values":["Structure-activity relationship of octreotide analogues labeled with rhenium and technetium-99m"]}]}],"canonical_facts":{"dc:contributor.advisor":["Lewis, Michael R.","Jurisson, Silvia S. (Silvia Sabine)"],"dc:creator":["Dannoon, Shorouk, 1982-"],"dc:date.accessioned":["2010-04-27T14:34:52Z"],"dc:date.available":["2010-04-27T14:34:52Z"],"dc:date.issued":["2009"],"dc:description":["Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 25, 2010).","The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.","Dissertation advisor: Dr. Silvia Jurisson and Dr. Mike Lewis.","Vita.","Includes bibliographical references.","Ph. D. University of Missouri--Columbia 2009.","Dissertations, Academic -- University of Missouri--Columbia -- Chemistry."],"dc:description.abstract":["The goal of this research is to cyclize octreotide analogues with ⁹⁹[supersript-m]Tc and ¹⁸⁶/¹⁸⁸Re radiometals to be used as diagnostic and therapeutic agents for neuroendocrine tumors, respectively. Several series of octreotide analogues that differ in their sequences, and/or coordination systems (S₂N₂ and S₃N) were developed. Their in vitro receptor binding affinity toward somatostatin receptors was measured via IC₅₀ studies. In vitro stability studies were carried out under physiological conditions on ⁹⁹[superscript-m]Tc-cyclized analogues in phosphate buffered saline, mouse serum, and under high cysteine concentration. The only analogue that expressed high receptor binding affinity was not stable at the tracer level; however, the other analogues were stable at the tracer level but at the expense of their receptor affinity. The effect of metal-cyclization on Tyr³-octreotate's receptor binding site was determined via three-dimensional molecular structure calculation, using two-dimensional NMR experiments as experimental constraints. From the obtained structures, it was concluded that the metal-cyclized Tyr³-octreotate's receptor binding site configuration was, to some extent, similar to that of the usually disulfide-cyclized counterpart."],"dc:identifier.doi":["https://doi.org/10.32469/10355/7019"],"dc:identifier.uri":["https://hdl.handle.net/10355/7019"],"dc:language":["English"],"dc:language.iso":["eng"],"dc:publisher":["University of Missouri--Columbia"],"dc:rights":["OpenAccess."],"dc:title":["Structure-activity relationship of octreotide analogues labeled with rhenium and technetium-99m"],"dc:type":["Thesis"],"thesis:degree_discipline":["Chemistry (MU)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["University of Missouri--Columbia"]},"updated_at":"2026-07-24T03:07:24Z"}