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

0479455 - ÚOCHB 2018 RIV GB eng J - Článek v odborném periodiku
Polášek, Miloslav - Yang, Y. - Schühle, D. T. - Yaseen, M. A. - Kim, Y. R. - Sung, Y. S. - Guimaraes, A. R. - Caravan, P.
Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer.
Scientific Reports. Roč. 7, Aug 14 (2017), č. článku 8114. ISSN 2045-2322. E-ISSN 2045-2322
Institucionální podpora: RVO:61388963
Klíčová slova: fibrosis * molecular imaging * pancreatic cancer
Obor OECD: Oncology
Impakt faktor: 4.122, rok: 2017
https://www.nature.com/articles/s41598-017-08838-6

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 (EP3533) 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 4.7T 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.
Trvalý link: http://hdl.handle.net/11104/0275447