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 pe...
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SAGE Publishing
2021-01-01
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| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2021/5540569 |
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| author | Solmaz AghaAmiri Jo Simien Alastair M. Thompson Julie Voss Sukhen C. Ghosh Servando Hernandez Vargas Sarah Kim Ali Azhdarinia Hop S. Tran Cao |
| author_facet | Solmaz AghaAmiri Jo Simien Alastair M. Thompson Julie Voss Sukhen C. Ghosh Servando Hernandez Vargas Sarah Kim Ali Azhdarinia Hop S. Tran Cao |
| author_sort | Solmaz AghaAmiri |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-74b901709eb247d592dd2599a37eb432 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-74b901709eb247d592dd2599a37eb4322025-02-03T10:12:45ZengSAGE PublishingMolecular Imaging1536-01212021-01-01202110.1155/2021/55405695540569Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast CancerSolmaz AghaAmiri0Jo Simien1Alastair M. Thompson2Julie Voss3Sukhen C. Ghosh4Servando Hernandez Vargas5Sarah Kim6Ali Azhdarinia7Hop S. Tran Cao8The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USAThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USADivision of Molecular and Clinical Medicine, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, UKThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USAThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USAThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USAThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USAThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USADepartment of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USABackground. 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.http://dx.doi.org/10.1155/2021/5540569 |
| spellingShingle | Solmaz AghaAmiri Jo Simien Alastair M. Thompson Julie Voss Sukhen C. Ghosh Servando Hernandez Vargas Sarah Kim Ali Azhdarinia Hop S. Tran Cao Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer Molecular Imaging |
| title | Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer |
| title_full | Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer |
| title_fullStr | Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer |
| title_full_unstemmed | Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer |
| title_short | Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer |
| title_sort | comparison of her2 targeted antibodies for fluorescence guided surgery in breast cancer |
| url | http://dx.doi.org/10.1155/2021/5540569 |
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