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Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor
Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermor...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493605/ https://www.ncbi.nlm.nih.gov/pubmed/23144978 http://dx.doi.org/10.1371/journal.pone.0048803 |
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author | Cohen, Gadi Lecht, Shimon Arien-Zakay, Hadar Ettinger, Keren Amsalem, Orit Oron-Herman, Mor Yavin, Eylon Prus, Diana Benita, Simon Nissan, Aviram Lazarovici, Philip |
author_facet | Cohen, Gadi Lecht, Shimon Arien-Zakay, Hadar Ettinger, Keren Amsalem, Orit Oron-Herman, Mor Yavin, Eylon Prus, Diana Benita, Simon Nissan, Aviram Lazarovici, Philip |
author_sort | Cohen, Gadi |
collection | PubMed |
description | Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues. |
format | Online Article Text |
id | pubmed-3493605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34936052012-11-09 Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor Cohen, Gadi Lecht, Shimon Arien-Zakay, Hadar Ettinger, Keren Amsalem, Orit Oron-Herman, Mor Yavin, Eylon Prus, Diana Benita, Simon Nissan, Aviram Lazarovici, Philip PLoS One Research Article Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues. Public Library of Science 2012-11-08 /pmc/articles/PMC3493605/ /pubmed/23144978 http://dx.doi.org/10.1371/journal.pone.0048803 Text en © 2012 Cohen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Cohen, Gadi Lecht, Shimon Arien-Zakay, Hadar Ettinger, Keren Amsalem, Orit Oron-Herman, Mor Yavin, Eylon Prus, Diana Benita, Simon Nissan, Aviram Lazarovici, Philip Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title | Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title_full | Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title_fullStr | Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title_full_unstemmed | Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title_short | Bio-Imaging of Colorectal Cancer Models Using Near Infrared Labeled Epidermal Growth Factor |
title_sort | bio-imaging of colorectal cancer models using near infrared labeled epidermal growth factor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493605/ https://www.ncbi.nlm.nih.gov/pubmed/23144978 http://dx.doi.org/10.1371/journal.pone.0048803 |
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