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

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

Blog Article

Abstract Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis velgen vff 12 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 15-1 shampoo 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.