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


Dominietto, Marco; Dobosz, Michael; Bürgi, Sandra; Renner, Anja; Zahlmann, Gudrun; Scheuer, Werner; Rudin, Markus (2017). Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy. European Radiology, 27(7):2894-2902.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Language:English
Date:July 2017
Deposited On:27 Mar 2018 14:27
Last Modified:13 Apr 2018 11:48
Publisher:Springer
ISSN:0938-7994
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s00330-016-4629-3
PubMed ID:27830379

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