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Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe
HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabele...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812989/ https://www.ncbi.nlm.nih.gov/pubmed/29445216 http://dx.doi.org/10.1038/s41598-018-21283-3 |
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author | Honarvar, Hadis Calce, Enrica Doti, Nunzianna Langella, Emma Orlova, Anna Buijs, Jos D’Amato, Valentina Bianco, Roberto Saviano, Michele Tolmachev, Vladimir De Luca, Stefania |
author_facet | Honarvar, Hadis Calce, Enrica Doti, Nunzianna Langella, Emma Orlova, Anna Buijs, Jos D’Amato, Valentina Bianco, Roberto Saviano, Michele Tolmachev, Vladimir De Luca, Stefania |
author_sort | Honarvar, Hadis |
collection | PubMed |
description | HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies. In this study, we evaluated a potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab portion. Its cellular uptake was investigated by mass spectrometry analysis of the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA chelator was conjugated to N-terminus of A9. (111)In-labeled A9 demonstrated nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution profile in NMRI mice. This study suggests that the peptide A9 represents a good lead candidate for development of molecular probe, to be used for imaging purposes and for the delivery of cytotoxic agents. |
format | Online Article Text |
id | pubmed-5812989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58129892018-02-21 Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe Honarvar, Hadis Calce, Enrica Doti, Nunzianna Langella, Emma Orlova, Anna Buijs, Jos D’Amato, Valentina Bianco, Roberto Saviano, Michele Tolmachev, Vladimir De Luca, Stefania Sci Rep Article HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies. In this study, we evaluated a potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab portion. Its cellular uptake was investigated by mass spectrometry analysis of the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA chelator was conjugated to N-terminus of A9. (111)In-labeled A9 demonstrated nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution profile in NMRI mice. This study suggests that the peptide A9 represents a good lead candidate for development of molecular probe, to be used for imaging purposes and for the delivery of cytotoxic agents. Nature Publishing Group UK 2018-02-14 /pmc/articles/PMC5812989/ /pubmed/29445216 http://dx.doi.org/10.1038/s41598-018-21283-3 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 Honarvar, Hadis Calce, Enrica Doti, Nunzianna Langella, Emma Orlova, Anna Buijs, Jos D’Amato, Valentina Bianco, Roberto Saviano, Michele Tolmachev, Vladimir De Luca, Stefania Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title | Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title_full | Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title_fullStr | Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title_full_unstemmed | Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title_short | Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe |
title_sort | evaluation of her2-specific peptide ligand for its employment as radiolabeled imaging probe |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812989/ https://www.ncbi.nlm.nih.gov/pubmed/29445216 http://dx.doi.org/10.1038/s41598-018-21283-3 |
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