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Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR

Truncated tissue factor (tTF)-NGR consists of the extracellular domain of the human TF and the binding motif NGR. tTF-NGR activates blood coagulation within the tumour vasculature following binding to CD13, and is overexpressed in the endothelial cells of tumour vessels, resulting in tumour vessel i...

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Autores principales: Höink, Anna, Persigehl, Thorsten, Kwiecien, Robert, Balthasar, Martin, Mesters, Rolf, Berdel, Wolfgang, Heindel, Walter, Bremer, Christoph, Schwöppe, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313167/
https://www.ncbi.nlm.nih.gov/pubmed/30655764
http://dx.doi.org/10.3892/ol.2018.9638
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author Höink, Anna
Persigehl, Thorsten
Kwiecien, Robert
Balthasar, Martin
Mesters, Rolf
Berdel, Wolfgang
Heindel, Walter
Bremer, Christoph
Schwöppe, Christian
author_facet Höink, Anna
Persigehl, Thorsten
Kwiecien, Robert
Balthasar, Martin
Mesters, Rolf
Berdel, Wolfgang
Heindel, Walter
Bremer, Christoph
Schwöppe, Christian
author_sort Höink, Anna
collection PubMed
description Truncated tissue factor (tTF)-NGR consists of the extracellular domain of the human TF and the binding motif NGR. tTF-NGR activates blood coagulation within the tumour vasculature following binding to CD13, and is overexpressed in the endothelial cells of tumour vessels, resulting in tumour vessel infarction and subsequent retardation/regression of tumour growth. The aim of the present study was to investigate gadofosveset-based real-time dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in evaluating the initial therapeutic effects of the anti-vascular tTF-NGR approach. DCE-MRI (3.0 T) was performed in human U87-glioblastoma tumour-bearing nude mice. During a dynamic T1w GE-sequence, a gadolinium-based blood pool contrast agent (gadofosveset) was injected via a tail vein catheter. Following the maximum contrast intensity inside the tumour being obtained, tTF-NGR was injected (controls received NaCl) and the contrast behaviour of the tumour was monitored by ROI analysis. The slope difference of signal intensities between controls and the tTF-NGR group was investigated, as well as the differences between the average area under the curve (AUC) of the two groups. The association between intensity, group (control vs. tTF-NGR group) and time was analysed by fitting a linear mixed model. Following the injection of tTF-NGR, the signal intensity inside the tumours exhibited a statistically significantly stronger average slope decrease compared with the signal intensity of the tumours in the NaCl group. Furthermore, the initial average AUC values of mice treated with tTF-NGR were 5.7% lower than the average AUC of the control animals (P<0.05). Gadofosveset-enhanced MRI enables the visualization of the initial tumour response to anti-vascular treatment in real-time. Considering the clinical application of tTF-NGR, this method may provide a simple alternative parameter for monitoring the tumour response to vascular disrupting agents and certain vascular targeting agents in humans.
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spelling pubmed-63131672019-01-17 Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR Höink, Anna Persigehl, Thorsten Kwiecien, Robert Balthasar, Martin Mesters, Rolf Berdel, Wolfgang Heindel, Walter Bremer, Christoph Schwöppe, Christian Oncol Lett Articles Truncated tissue factor (tTF)-NGR consists of the extracellular domain of the human TF and the binding motif NGR. tTF-NGR activates blood coagulation within the tumour vasculature following binding to CD13, and is overexpressed in the endothelial cells of tumour vessels, resulting in tumour vessel infarction and subsequent retardation/regression of tumour growth. The aim of the present study was to investigate gadofosveset-based real-time dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in evaluating the initial therapeutic effects of the anti-vascular tTF-NGR approach. DCE-MRI (3.0 T) was performed in human U87-glioblastoma tumour-bearing nude mice. During a dynamic T1w GE-sequence, a gadolinium-based blood pool contrast agent (gadofosveset) was injected via a tail vein catheter. Following the maximum contrast intensity inside the tumour being obtained, tTF-NGR was injected (controls received NaCl) and the contrast behaviour of the tumour was monitored by ROI analysis. The slope difference of signal intensities between controls and the tTF-NGR group was investigated, as well as the differences between the average area under the curve (AUC) of the two groups. The association between intensity, group (control vs. tTF-NGR group) and time was analysed by fitting a linear mixed model. Following the injection of tTF-NGR, the signal intensity inside the tumours exhibited a statistically significantly stronger average slope decrease compared with the signal intensity of the tumours in the NaCl group. Furthermore, the initial average AUC values of mice treated with tTF-NGR were 5.7% lower than the average AUC of the control animals (P<0.05). Gadofosveset-enhanced MRI enables the visualization of the initial tumour response to anti-vascular treatment in real-time. Considering the clinical application of tTF-NGR, this method may provide a simple alternative parameter for monitoring the tumour response to vascular disrupting agents and certain vascular targeting agents in humans. D.A. Spandidos 2019-01 2018-10-29 /pmc/articles/PMC6313167/ /pubmed/30655764 http://dx.doi.org/10.3892/ol.2018.9638 Text en Copyright: © Höink et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Höink, Anna
Persigehl, Thorsten
Kwiecien, Robert
Balthasar, Martin
Mesters, Rolf
Berdel, Wolfgang
Heindel, Walter
Bremer, Christoph
Schwöppe, Christian
Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title_full Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title_fullStr Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title_full_unstemmed Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title_short Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR
title_sort gadofosveset-enhanced mri as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor ttf-ngr
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313167/
https://www.ncbi.nlm.nih.gov/pubmed/30655764
http://dx.doi.org/10.3892/ol.2018.9638
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