{"id":4031,"date":"2022-10-19T12:05:08","date_gmt":"2022-10-19T10:05:08","guid":{"rendered":"https:\/\/www.m2olie.de\/?post_type=publications&#038;p=4031"},"modified":"2024-02-02T12:06:13","modified_gmt":"2024-02-02T11:06:13","slug":"synthesis-of-a-new-bifunctional-cross-bridged-chelating-agent-peptide-conjugation-and-comparison-of-68ga-labeling-and-complex-stability-characteristics-with-established-chelators","status":"publish","type":"publications","link":"https:\/\/www.m2olie.de\/en\/publications\/synthesis-of-a-new-bifunctional-cross-bridged-chelating-agent-peptide-conjugation-and-comparison-of-68ga-labeling-and-complex-stability-characteristics-with-established-chelators\/","title":{"rendered":"Synthesis of a new bifunctional cross-bridged chelating agent, peptide conjugation, and comparison of 68Ga-labeling and complex stability characteristics with established chelators"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Damerow H, W\u00e4ngler B, Schirrmacher R, Fricker G, W\u00e4ngler C* (2023) Synthesis of a new bifunctional cross-bridged chelating agent, peptide conjugation, and comparison of <sup>68<\/sup>Ga-labeling and complex stability characteristics with established chelators. <em>ChemMedChem 18(1)<\/em>, e202200495. <a rel=\"noreferrer noopener\" href=\"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full\/10.1002\/cmdc.202200495\" target=\"_blank\">DOI: 10.1002\/cmdc.202200495<\/a>.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"d95155353\">Graphical Abstract<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>The new backbone-modified<\/strong> bifunctional cross-bridged chelating agent CB-DO2A-GA was developed, introduced into the peptide Tyr<sup>3<\/sup>-octreotate and compared to the established chelators DOTA, NODA-GA and DOTA-GA in terms of <sup>68<\/sup>Ga-radiolabeling efficiency and kinetic inertness of the formed complexes.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><a href=\"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/cms\/asset\/a3c00e69-447c-4d6d-9dcb-793dbb2027f8\/cmdc202200495-toc-0001-m.jpg\" target=\"_blank\" rel=\"noreferrer noopener\"><img decoding=\"async\" src=\"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/cms\/asset\/186ada36-721e-418a-be16-7fc3db5026af\/cmdc202200495-toc-0001-m.png\" alt=\"Description unavailable\" title=\"Description unavailable\" \/><\/a><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"d95155400\">Abstract<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">[<sup>68<\/sup>Ga]Ga<sup>3+<\/sup> can be introduced into receptor-specific peptidic carriers <em>via<\/em> different chelators to obtain radiotracers for Positron Emission Tomography imaging and the chosen chelating agent considerably influences the <em>in\u2005vivo<\/em> pharmacokinetics of the corresponding radiopeptides. A chelator that should be a valuable alternative to established chelating agents for <sup>68<\/sup>Ga-radiolabeling of peptides would be a backbone-functionalized variant of the chelator CB-DO2A. Here, the bifunctional cross-bridged chelating agent CB-DO2A-GA was developed and compared to the established chelators DOTA, NODA-GA and DOTA-GA. For this purpose, CB-DO2A-GA(<em>t<\/em>Bu)<sub>2<\/sub> was introduced into the peptide Tyr<sup>3<\/sup>-octreotate (TATE) and in direct comparison to the corresponding DOTA-, NODA-GA-, and DOTA-GA-modified TATE analogs, CB-DO2A-GA-TATE required harsher reaction conditions for <sup>68<\/sup>Ga-incorporation. Regarding the hydrophilicity profile of the resulting radiopeptides, a decrease in hydrophilicity from [<sup>68<\/sup>Ga]Ga-DOTA-GA-TATE (log<sub><em>D<\/em>(7.4)<\/sub> of \u22124.11\u00b10.11) to [<sup>68<\/sup>Ga]Ga-CB-DO2A-GA-TATE (\u22123.02\u00b10.08) was observed. Assessing the stability against metabolic degradation and complex challenge, [<sup>68<\/sup>Ga]Ga-CB-DO2A-GA demonstrated a very high kinetic inertness, exceeding that of [<sup>68<\/sup>Ga]Ga-DOTA-GA. Therefore, CB-DO2A-GA is a valuable alternative to established chelating agents for <sup>68<\/sup>Ga-radiolabeling of peptides, especially when the formation of a very stable, positively charged <sup>68<\/sup>Ga-complex is pursued.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"featured_media":0,"comment_status":"open","ping_status":"closed","template":"","meta":{"footnotes":""},"categories":[],"class_list":["post-4031","publications","type-publications","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/4031","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/types\/publications"}],"replies":[{"embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/comments?post=4031"}],"version-history":[{"count":1,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/4031\/revisions"}],"predecessor-version":[{"id":4032,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/4031\/revisions\/4032"}],"wp:attachment":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/media?parent=4031"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/categories?post=4031"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}