{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/19195"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/19195","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Rhenium and technetium-labeled progestins, the development of receptor-directed agents for diagnostic imaging or therapy","abstract":"In order to investigate the possibility of developing diagnostic imaging agents for steroid receptor-positive tumors that are labeled with the readily available radionuclide technetium-99m, three conjugate systems have been prepared in which a progestin is linked to a metal chelate system. These are bis-amino bis-thiol (BAT or N$\\sb2$S$\\sb2$) systems and are linked through carbon-21 of progesterone or the 17$\\alpha$- or 11$\\beta$-position of a nortestosterone type progestin. As a model for technetium-labeled complexes, all three chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomeric products in each of these systems, a syn pair and an anti pair (linker methylene vs. rhenium-oxo, relative to the N$\\sb2$S$\\sb2$ plane) were separated in the 17$\\alpha$-substituted series (B6syn1,2 and B6anti1,2), a syn pair was isolated in the 21-substituted series (A4syn1,2), and a syn pair and the two individual anti diastereomers were separated in the 11$\\beta$-substituted series (C15syn1,2, C15anti1, and C15anti2). In competitive radiometric receptor binding assays, the 21-, and 17$\\alpha$-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11$\\beta$-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The 11$\\beta$-linked syn system was also prepared in Tc-99 labeled form (5). The two anti diastereomers (5anti1 and 5anti2) had affinities of 7% and 47%, and the syn pair (5syn1,2) had an affinity of 25% relative to R5020. The latter findings indicate that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. Tc-99m and Re-186 analogs of the 11$\\beta$-linked syn system were then prepared (6 and 7). In vitro studies of the Tc-99m and Re-186 systems showed that the conjugates bind with the metal-oxo core intact and that the specific to non-specific binding ratios for the Tc-99m and Re-186 analogs are 75/25 and 54/46, respectively. In vivo, conjugates 6 and 7 showed receptor mediated uptake in rat uterus but also high uptake in non-target tissues. The high lipophilicity of the chelates is presumed to be the reason for the large non-selective binding. Modified, less lipophilic systems, may be useful in vivo as receptor directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.","abstract_html":"In order to investigate the possibility of developing diagnostic imaging agents for steroid receptor-positive tumors that are labeled with the readily available radionuclide technetium-99m, three conjugate systems have been prepared in which a progestin is linked to a metal chelate system. These are bis-amino bis-thiol (BAT or N$\\sb2$S$\\sb2$) systems and are linked through carbon-21 of progesterone or the 17<span class=\"etd-inline-math\">&alpha;</span>- or 11<span class=\"etd-inline-math\">&beta;</span>-position of a nortestosterone type progestin. As a model for technetium-labeled complexes, all three chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomeric products in each of these systems, a syn pair and an anti pair (linker methylene vs. rhenium-oxo, relative to the N$\\sb2$S$\\sb2$ plane) were separated in the 17<span class=\"etd-inline-math\">&alpha;</span>-substituted series (B6syn1,2 and B6anti1,2), a syn pair was isolated in the 21-substituted series (A4syn1,2), and a syn pair and the two individual anti diastereomers were separated in the 11<span class=\"etd-inline-math\">&beta;</span>-substituted series (C15syn1,2, C15anti1, and C15anti2). In competitive radiometric receptor binding assays, the 21-, and 17<span class=\"etd-inline-math\">&alpha;</span>-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11<span class=\"etd-inline-math\">&beta;</span>-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The 11<span class=\"etd-inline-math\">&beta;</span>-linked syn system was also prepared in Tc-99 labeled form (5). The two anti diastereomers (5anti1 and 5anti2) had affinities of 7% and 47%, and the syn pair (5syn1,2) had an affinity of 25% relative to R5020. The latter findings indicate that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. Tc-99m and Re-186 analogs of the 11<span class=\"etd-inline-math\">&beta;</span>-linked syn system were then prepared (6 and 7). In vitro studies of the Tc-99m and Re-186 systems showed that the conjugates bind with the metal-oxo core intact and that the specific to non-specific binding ratios for the Tc-99m and Re-186 analogs are 75/25 and 54/46, respectively. In vivo, conjugates 6 and 7 showed receptor mediated uptake in rat uterus but also high uptake in non-target tissues. The high lipophilicity of the chelates is presumed to be the reason for the large non-selective binding. Modified, less lipophilic systems, may be useful in vivo as receptor directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.","abstract_has_math":true,"creators":["DiZio, James Patrick"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T11:59:49Z","date_published":"2011-05-07T11:59:49Z","updated_at":"2026-07-22T22:25:12Z","subjects":["Chemistry, Organic","Chemistry, Pharmaceutical","Chemistry, Radiation"],"languages":["eng"],"rights":["Copyright 1991 DiZio, James Patrick"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI9210785","AAI9210785"],"render_values":[{"text":"(UMI)AAI9210785","href":null,"code":true},{"text":"AAI9210785","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/19195","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["DiZio, James Patrick"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T11:59:49Z","10000-01-01","1991"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic","Chemistry, Pharmaceutical","Chemistry, Radiation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1991 DiZio, James Patrick"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI9210785","AAI9210785","http://hdl.handle.net/2142/19195"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["In order to investigate the possibility of developing diagnostic imaging agents for steroid receptor-positive tumors that are labeled with the readily available radionuclide technetium-99m, three conjugate systems have been prepared in which a progestin is linked to a metal chelate system. These are bis-amino bis-thiol (BAT or N$\\sb2$S$\\sb2$) systems and are linked through carbon-21 of progesterone or the 17$\\alpha$- or 11$\\beta$-position of a nortestosterone type progestin. As a model for technetium-labeled complexes, all three chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomeric products in each of these systems, a syn pair and an anti pair (linker methylene vs. rhenium-oxo, relative to the N$\\sb2$S$\\sb2$ plane) were separated in the 17$\\alpha$-substituted series (B6syn1,2 and B6anti1,2), a syn pair was isolated in the 21-substituted series (A4syn1,2), and a syn pair and the two individual anti diastereomers were separated in the 11$\\beta$-substituted series (C15syn1,2, C15anti1, and C15anti2). In competitive radiometric receptor binding assays, the 21-, and 17$\\alpha$-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11$\\beta$-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The 11$\\beta$-linked syn system was also prepared in Tc-99 labeled form (5). The two anti diastereomers (5anti1 and 5anti2) had affinities of 7% and 47%, and the syn pair (5syn1,2) had an affinity of 25% relative to R5020. The latter findings indicate that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. Tc-99m and Re-186 analogs of the 11$\\beta$-linked syn system were then prepared (6 and 7). In vitro studies of the Tc-99m and Re-186 systems showed that the conjugates bind with the metal-oxo core intact and that the specific to non-specific binding ratios for the Tc-99m and Re-186 analogs are 75/25 and 54/46, respectively. In vivo, conjugates 6 and 7 showed receptor mediated uptake in rat uterus but also high uptake in non-target tissues. The high lipophilicity of the chelates is presumed to be the reason for the large non-selective binding. Modified, less lipophilic systems, may be useful in vivo as receptor directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.","Made available in DSpace on 2011-05-07T11:59:49Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9210785.pdf: 4647309 bytes, checksum: b78f1e5d5733345fa8e09aa0adeb7717 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:35:18Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:13:52-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Rhenium and technetium-labeled progestins, the development of receptor-directed agents for diagnostic imaging or therapy"]}]}],"canonical_facts":{"dc:creator":["DiZio, James Patrick"],"dc:date":["2011-05-07T11:59:49Z","10000-01-01","1991"],"dc:description":["In order to investigate the possibility of developing diagnostic imaging agents for steroid receptor-positive tumors that are labeled with the readily available radionuclide technetium-99m, three conjugate systems have been prepared in which a progestin is linked to a metal chelate system. These are bis-amino bis-thiol (BAT or N$\\sb2$S$\\sb2$) systems and are linked through carbon-21 of progesterone or the 17$\\alpha$- or 11$\\beta$-position of a nortestosterone type progestin. As a model for technetium-labeled complexes, all three chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomeric products in each of these systems, a syn pair and an anti pair (linker methylene vs. rhenium-oxo, relative to the N$\\sb2$S$\\sb2$ plane) were separated in the 17$\\alpha$-substituted series (B6syn1,2 and B6anti1,2), a syn pair was isolated in the 21-substituted series (A4syn1,2), and a syn pair and the two individual anti diastereomers were separated in the 11$\\beta$-substituted series (C15syn1,2, C15anti1, and C15anti2). In competitive radiometric receptor binding assays, the 21-, and 17$\\alpha$-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11$\\beta$-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The 11$\\beta$-linked syn system was also prepared in Tc-99 labeled form (5). The two anti diastereomers (5anti1 and 5anti2) had affinities of 7% and 47%, and the syn pair (5syn1,2) had an affinity of 25% relative to R5020. The latter findings indicate that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. Tc-99m and Re-186 analogs of the 11$\\beta$-linked syn system were then prepared (6 and 7). In vitro studies of the Tc-99m and Re-186 systems showed that the conjugates bind with the metal-oxo core intact and that the specific to non-specific binding ratios for the Tc-99m and Re-186 analogs are 75/25 and 54/46, respectively. In vivo, conjugates 6 and 7 showed receptor mediated uptake in rat uterus but also high uptake in non-target tissues. The high lipophilicity of the chelates is presumed to be the reason for the large non-selective binding. Modified, less lipophilic systems, may be useful in vivo as receptor directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.","Made available in DSpace on 2011-05-07T11:59:49Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9210785.pdf: 4647309 bytes, checksum: b78f1e5d5733345fa8e09aa0adeb7717 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:35:18Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:13:52-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["(UMI)AAI9210785","AAI9210785","http://hdl.handle.net/2142/19195"],"dc:language":["eng"],"dc:rights":["Copyright 1991 DiZio, James Patrick"],"dc:subject":["Chemistry, Organic","Chemistry, Pharmaceutical","Chemistry, Radiation"],"dc:title":["Rhenium and technetium-labeled progestins, the development of receptor-directed agents for diagnostic imaging or therapy"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:12Z"}