Solmaz AghaAmiri, Jo Simien, Alastair M Thompson, Julie Voss, Sukhen C Ghosh, Servando Hernandez Vargas, Sarah Kim, Ali Azhdarinia, Hop S Tran Cao
{"title":"乳腺癌荧光引导手术中her2靶向抗体的比较","authors":"Solmaz AghaAmiri, Jo Simien, Alastair M Thompson, Julie Voss, Sukhen C Ghosh, Servando Hernandez Vargas, Sarah Kim, Ali Azhdarinia, Hop S Tran Cao","doi":"10.1155/2021/5540569","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).</p><p><strong>Methods: </strong>mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative <i>in vitro</i> assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with <sup>89</sup>Zr. <i>In vitro</i> binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for <i>in vivo</i> and <i>ex vivo</i> fluorescence imaging.</p><p><strong>Results: </strong><i>In vitro</i> findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. <i>In vivo</i> and <i>ex vivo</i> studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. <i>In vivo</i> HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.</p><p><strong>Conclusions: </strong>We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2021-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205604/pdf/","citationCount":"1","resultStr":"{\"title\":\"Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer.\",\"authors\":\"Solmaz AghaAmiri, Jo Simien, Alastair M Thompson, Julie Voss, Sukhen C Ghosh, Servando Hernandez Vargas, Sarah Kim, Ali Azhdarinia, Hop S Tran Cao\",\"doi\":\"10.1155/2021/5540569\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).</p><p><strong>Methods: </strong>mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative <i>in vitro</i> assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with <sup>89</sup>Zr. <i>In vitro</i> binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for <i>in vivo</i> and <i>ex vivo</i> fluorescence imaging.</p><p><strong>Results: </strong><i>In vitro</i> findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. <i>In vivo</i> and <i>ex vivo</i> studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. <i>In vivo</i> HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.</p><p><strong>Conclusions: </strong>We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.</p>\",\"PeriodicalId\":18855,\"journal\":{\"name\":\"Molecular Imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2021-02-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205604/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2021/5540569\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2021/5540569","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer.
Background: Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).
Methods: mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging.
Results: In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.
Conclusions: We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.
Molecular ImagingBiochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
期刊介绍:
Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.