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European Radiology
Published in: European Radiology 7/2017

01-07-2017 | Oncology

Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

Authors: Marco Dominietto, Michael Dobosz, Sandra Bürgi, Anja Renner, Gudrun Zahlmann, Werner Scheuer, Markus Rudin

Published in: European Radiology | Issue 7/2017

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Abstract

Objectives

This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity.

Methods

Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results.

Results

Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups.

Conclusions

Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time.

Key Points

• VEGF inhibition affects only the highly angiogenic region and small capillaries network
• VEGF inhibition is transient in time
• Tumour volume is not affected by anti-angiogenic treatment
• VEGF inhibition also influences the architecture of necrotic regions
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Metadata
Title
Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy
Authors
Marco Dominietto
Michael Dobosz
Sandra Bürgi
Anja Renner
Gudrun Zahlmann
Werner Scheuer
Markus Rudin
Publication date
01-07-2017
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 7/2017
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-016-4629-3

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