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

Miloslav Polasek, Yan Yang, Daniel T. Schühle, Mohammad A. Yaseen, Young R. Kim, Yu Sub Sung, Alexander R. Guimaraes, Peter Caravan

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13 Scopus citations

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.

Original languageEnglish (US)
Article number8114
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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    Polasek, M., Yang, Y., Schühle, D. T., Yaseen, M. A., Kim, Y. R., Sung, Y. S., Guimaraes, A. R., & Caravan, P. (2017). Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer. Scientific Reports, 7(1), [8114]. https://doi.org/10.1038/s41598-017-08838-6