Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)

Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine...

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Autores principales: McKnight, Brooke N., Kuda-Wedagedara, Akhila N. W., Sevak, Kuntal K., Abdel-Atti, Dalya, Wiesend, Wendy N., Ku, Anson, Selvakumar, Dakshnamurthy, Carlin, Sean D., Lewis, Jason S., Viola-Villegas, Nerissa T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998059/
https://www.ncbi.nlm.nih.gov/pubmed/29899472
http://dx.doi.org/10.1038/s41598-018-27454-6
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author McKnight, Brooke N.
Kuda-Wedagedara, Akhila N. W.
Sevak, Kuntal K.
Abdel-Atti, Dalya
Wiesend, Wendy N.
Ku, Anson
Selvakumar, Dakshnamurthy
Carlin, Sean D.
Lewis, Jason S.
Viola-Villegas, Nerissa T.
author_facet McKnight, Brooke N.
Kuda-Wedagedara, Akhila N. W.
Sevak, Kuntal K.
Abdel-Atti, Dalya
Wiesend, Wendy N.
Ku, Anson
Selvakumar, Dakshnamurthy
Carlin, Sean D.
Lewis, Jason S.
Viola-Villegas, Nerissa T.
author_sort McKnight, Brooke N.
collection PubMed
description Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine kinases attractive targets. MEHD7945A or duligotuzumab is a single immunotherapy agent that dually targets both molecular signatures. In this study, a positron emission tomography (PET) companion diagnostic to MEHD7945A is reported and evaluated in pancreatic cancer. Tumor accretion and whole body pharmacokinetics of (89)Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined.
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spelling pubmed-59980592018-06-21 Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab) McKnight, Brooke N. Kuda-Wedagedara, Akhila N. W. Sevak, Kuntal K. Abdel-Atti, Dalya Wiesend, Wendy N. Ku, Anson Selvakumar, Dakshnamurthy Carlin, Sean D. Lewis, Jason S. Viola-Villegas, Nerissa T. Sci Rep Article Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine kinases attractive targets. MEHD7945A or duligotuzumab is a single immunotherapy agent that dually targets both molecular signatures. In this study, a positron emission tomography (PET) companion diagnostic to MEHD7945A is reported and evaluated in pancreatic cancer. Tumor accretion and whole body pharmacokinetics of (89)Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined. Nature Publishing Group UK 2018-06-13 /pmc/articles/PMC5998059/ /pubmed/29899472 http://dx.doi.org/10.1038/s41598-018-27454-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
McKnight, Brooke N.
Kuda-Wedagedara, Akhila N. W.
Sevak, Kuntal K.
Abdel-Atti, Dalya
Wiesend, Wendy N.
Ku, Anson
Selvakumar, Dakshnamurthy
Carlin, Sean D.
Lewis, Jason S.
Viola-Villegas, Nerissa T.
Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title_full Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title_fullStr Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title_full_unstemmed Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title_short Imaging EGFR and HER3 through (89)Zr-labeled MEHD7945A (Duligotuzumab)
title_sort imaging egfr and her3 through (89)zr-labeled mehd7945a (duligotuzumab)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998059/
https://www.ncbi.nlm.nih.gov/pubmed/29899472
http://dx.doi.org/10.1038/s41598-018-27454-6
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