Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
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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 jumbo pe?ete yüzü?ü 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 cadbury eclairs chocolate price 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.