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Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (...

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Autores principales: Polasek, Miloslav, Yang, Yan, Schühle, Daniel T., Yaseen, Mohammad A., Kim, Young R., Sung, Yu Sub, Guimaraes, Alexander R., Caravan, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556073/
https://www.ncbi.nlm.nih.gov/pubmed/28808290
http://dx.doi.org/10.1038/s41598-017-08838-6
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author Polasek, Miloslav
Yang, Yan
Schühle, Daniel T.
Yaseen, Mohammad A.
Kim, Young R.
Sung, Yu Sub
Guimaraes, Alexander R.
Caravan, Peter
author_facet Polasek, Miloslav
Yang, Yan
Schühle, Daniel T.
Yaseen, Mohammad A.
Kim, Young R.
Sung, Yu Sub
Guimaraes, Alexander R.
Caravan, Peter
author_sort Polasek, Miloslav
collection PubMed
description Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4.7 T before, during and up to 60 min after i.v. injection of EP-3533, or of its non-binding isomer EP-3612. Ex-vivo quantification of gadolinium showed significantly higher uptake of EP-3533 compared to EP-3612 in tumours, but not in surrounding tissue (blood, muscle). Uptake of EP-3533 visualized in T1-weighted MRI correlated well with spatial distribution of collagen determined by second harmonic generation imaging. Differences in the tumour pharmacokinetic profiles of EP-3533 and EP-3612 were utilized to distinguish specific binding to tumour collagen from non-specific uptake. A model-free pharmacokinetic measurement based on area under the curve was identified as a robust imaging biomarker of fibrosis. Collagen-targeted molecular MRI with EP-3533 represents a new tool for non-invasive visualization and quantification of fibrosis in tumour tissue.
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spelling pubmed-55560732017-08-16 Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer Polasek, Miloslav Yang, Yan Schühle, Daniel T. Yaseen, Mohammad A. Kim, Young R. Sung, Yu Sub Guimaraes, Alexander R. Caravan, Peter Sci Rep Article Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4.7 T before, during and up to 60 min after i.v. injection of EP-3533, or of its non-binding isomer EP-3612. Ex-vivo quantification of gadolinium showed significantly higher uptake of EP-3533 compared to EP-3612 in tumours, but not in surrounding tissue (blood, muscle). Uptake of EP-3533 visualized in T1-weighted MRI correlated well with spatial distribution of collagen determined by second harmonic generation imaging. Differences in the tumour pharmacokinetic profiles of EP-3533 and EP-3612 were utilized to distinguish specific binding to tumour collagen from non-specific uptake. A model-free pharmacokinetic measurement based on area under the curve was identified as a robust imaging biomarker of fibrosis. Collagen-targeted molecular MRI with EP-3533 represents a new tool for non-invasive visualization and quantification of fibrosis in tumour tissue. Nature Publishing Group UK 2017-08-14 /pmc/articles/PMC5556073/ /pubmed/28808290 http://dx.doi.org/10.1038/s41598-017-08838-6 Text en © The Author(s) 2017 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
Polasek, Miloslav
Yang, Yan
Schühle, Daniel T.
Yaseen, Mohammad A.
Kim, Young R.
Sung, Yu Sub
Guimaraes, Alexander R.
Caravan, Peter
Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title_full Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title_fullStr Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title_full_unstemmed Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title_short Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
title_sort molecular mr imaging of fibrosis in a mouse model of pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556073/
https://www.ncbi.nlm.nih.gov/pubmed/28808290
http://dx.doi.org/10.1038/s41598-017-08838-6
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