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 Guimaraes, Peter Caravan

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Molecular Imaging
Pancreatic Neoplasms
Fibrosis
Collagen
Neoplasms
Gadolinium
Collagen Type I
Pharmacokinetics
Area Under Curve
Pancreas
Adenocarcinoma
Biomarkers
Magnetic Resonance Imaging
Muscles
Injections

ASJC Scopus subject areas

  • General

Cite this

Polasek, M., Yang, Y., Schühle, D. T., Yaseen, M. A., Kim, Y. R., Sung, Y. S., ... 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

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; Caravan, Peter.

In: Scientific Reports, Vol. 7, No. 1, 8114, 01.12.2017.

Research output: Contribution to journalArticle

Polasek, M, Yang, Y, Schühle, DT, Yaseen, MA, Kim, YR, Sung, YS, Guimaraes, A & Caravan, P 2017, 'Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer', Scientific Reports, vol. 7, no. 1, 8114. https://doi.org/10.1038/s41598-017-08838-6
Polasek M, Yang Y, Schühle DT, Yaseen MA, Kim YR, Sung YS et al. Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer. Scientific Reports. 2017 Dec 1;7(1). 8114. https://doi.org/10.1038/s41598-017-08838-6
Polasek, Miloslav ; Yang, Yan ; Schühle, Daniel T. ; Yaseen, Mohammad A. ; Kim, Young R. ; Sung, Yu Sub ; Guimaraes, Alexander ; Caravan, Peter. / Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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