Hoeink, Anna, Persigehl, Thorsten, Kwiecien, Robert, Balthasar, Martin, Mesters, Rolf, Berdel, Wolfgang, Heindel, Walter, Bremer, Christoph and Schwoeppe, Christian (2019). Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR. Oncol. Lett., 17 (1). S. 270 - 281. ATHENS: SPANDIDOS PUBL LTD. ISSN 1792-1082
Full text not available from this repository.Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-140412 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.3892/ol.2018.9638 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Oncol. Lett. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 17 | ||||||||||||||||||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 270 - 281 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2019 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | SPANDIDOS PUBL LTD | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | ATHENS | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1792-1082 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/14041 |
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