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

Abstract 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 c...

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Autores principales:	Miloslav Polasek, Yan Yang, Daniel T. Schühle, Mohammad A. Yaseen, Young R. Kim, Yu Sub Sung, Alexander R. Guimaraes, Peter Caravan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3d6d4e3ab7149cd8ad953c61bcdbb76
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spelling	oai:doaj.org-article:d3d6d4e3ab7149cd8ad953c61bcdbb762021-12-02T12:32:45ZMolecular MR imaging of fibrosis in a mouse model of pancreatic cancer10.1038/s41598-017-08838-62045-2322https://doaj.org/article/d3d6d4e3ab7149cd8ad953c61bcdbb762017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08838-6https://doaj.org/toc/2045-2322Abstract 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.Miloslav PolasekYan YangDaniel T. SchühleMohammad A. YaseenYoung R. KimYu Sub SungAlexander R. GuimaraesPeter CaravanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miloslav Polasek Yan Yang Daniel T. Schühle Mohammad A. Yaseen Young R. Kim Yu Sub Sung Alexander R. Guimaraes Peter Caravan Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
description	Abstract 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.
format	article
author	Miloslav Polasek Yan Yang Daniel T. Schühle Mohammad A. Yaseen Young R. Kim Yu Sub Sung Alexander R. Guimaraes Peter Caravan
author_facet	Miloslav Polasek Yan Yang Daniel T. Schühle Mohammad A. Yaseen Young R. Kim Yu Sub Sung Alexander R. Guimaraes Peter Caravan
author_sort	Miloslav Polasek
title	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_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_sort	molecular mr imaging of fibrosis in a mouse model of pancreatic cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d3d6d4e3ab7149cd8ad953c61bcdbb76
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Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

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