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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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Autores principales: AghaAmiri, Solmaz, Simien, Jo, Thompson, Alastair M., Voss, Julie, Ghosh, Sukhen C., Hernandez Vargas, Servando, Kim, Sarah, Azhdarinia, Ali, Tran Cao, Hop S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205604/
https://www.ncbi.nlm.nih.gov/pubmed/34194285
http://dx.doi.org/10.1155/2021/5540569
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author AghaAmiri, Solmaz
Simien, Jo
Thompson, Alastair M.
Voss, Julie
Ghosh, Sukhen C.
Hernandez Vargas, Servando
Kim, Sarah
Azhdarinia, Ali
Tran Cao, Hop S.
author_facet AghaAmiri, Solmaz
Simien, Jo
Thompson, Alastair M.
Voss, Julie
Ghosh, Sukhen C.
Hernandez Vargas, Servando
Kim, Sarah
Azhdarinia, Ali
Tran Cao, Hop S.
author_sort AghaAmiri, Solmaz
collection PubMed
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 (89)Zr. 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.
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spelling pubmed-82056042021-06-29 Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer AghaAmiri, Solmaz Simien, Jo Thompson, Alastair M. Voss, Julie Ghosh, Sukhen C. Hernandez Vargas, Servando Kim, Sarah Azhdarinia, Ali Tran Cao, Hop S. Mol Imaging Research Article 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 (89)Zr. 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. Hindawi 2021-02-02 /pmc/articles/PMC8205604/ /pubmed/34194285 http://dx.doi.org/10.1155/2021/5540569 Text en Copyright © 2021 Solmaz AghaAmiri et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
AghaAmiri, Solmaz
Simien, Jo
Thompson, Alastair M.
Voss, Julie
Ghosh, Sukhen C.
Hernandez Vargas, Servando
Kim, Sarah
Azhdarinia, Ali
Tran Cao, Hop S.
Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205604/
https://www.ncbi.nlm.nih.gov/pubmed/34194285
http://dx.doi.org/10.1155/2021/5540569
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