Aidan A Bender, Connor K Holiski, Mary Embree, Heather M Hennkens, John R Klaehn, Ellie Lundgreen, Andrew G Roberts, Peter R Zalupski, Tara Mastren
{"title":"Pursuing theranostics: a multimodal architecture approach.","authors":"Aidan A Bender, Connor K Holiski, Mary Embree, Heather M Hennkens, John R Klaehn, Ellie Lundgreen, Andrew G Roberts, Peter R Zalupski, Tara Mastren","doi":"10.1039/d4sd00221k","DOIUrl":null,"url":null,"abstract":"<p><p>Theranostics is a field of nuclear medicine which uses the same targeting vector and chelating system for both a diagnostic and therapeutic radionuclide, allowing for uniformity in imaging and treatment. This growing field requires the development of more flexible chelate systems that permit novel targeting strategies. Toward this end, a multimodal architecture has been realized, making use of a phosphazene-based core and click chemistry to achieve a flexible and customizable scaffold. The six arm phosphazene-based core can scaffold six DTPA chelating motifs or a mixed set of 3 : 3 DTPA : DFO chelates resulting in two multimodal compounds, pDbDt and pDbDtDf, respectively. Terbium complexes displayed strong luminescence, supporting that the structures act as an organic antenna for luminescence. Metal displacement titration studies confirmed the desired structures as well as the capability for heterometallic labeling of the structures. These structures were found to have high thermal and biological stability <i>in vitro</i>. Radiolabeling of each compound resulted in high molar activity labeling of each compound: 169 MBq nmol<sup>-1</sup>: [<sup>161</sup>Tb]Tb-pDbDt, 170 MBq nmol<sup>-1</sup>: [<sup>89</sup>Zr]Zr-pDbDtDf, and the mixed radiolabeling illustrated chelation of both radionuclides in a 1 : 1 ratio. This multimodal architecture is promising as a heterometallic structure for coupling of both a diagnostic and a therapeutic radionuclide with a highly customizable core structure.</p>","PeriodicalId":74786,"journal":{"name":"Sensors & diagnostics","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528688/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sensors & diagnostics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1039/d4sd00221k","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Theranostics is a field of nuclear medicine which uses the same targeting vector and chelating system for both a diagnostic and therapeutic radionuclide, allowing for uniformity in imaging and treatment. This growing field requires the development of more flexible chelate systems that permit novel targeting strategies. Toward this end, a multimodal architecture has been realized, making use of a phosphazene-based core and click chemistry to achieve a flexible and customizable scaffold. The six arm phosphazene-based core can scaffold six DTPA chelating motifs or a mixed set of 3 : 3 DTPA : DFO chelates resulting in two multimodal compounds, pDbDt and pDbDtDf, respectively. Terbium complexes displayed strong luminescence, supporting that the structures act as an organic antenna for luminescence. Metal displacement titration studies confirmed the desired structures as well as the capability for heterometallic labeling of the structures. These structures were found to have high thermal and biological stability in vitro. Radiolabeling of each compound resulted in high molar activity labeling of each compound: 169 MBq nmol-1: [161Tb]Tb-pDbDt, 170 MBq nmol-1: [89Zr]Zr-pDbDtDf, and the mixed radiolabeling illustrated chelation of both radionuclides in a 1 : 1 ratio. This multimodal architecture is promising as a heterometallic structure for coupling of both a diagnostic and a therapeutic radionuclide with a highly customizable core structure.