Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Hoeink, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Persigehl, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Kwiecien, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Balthasar, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mesters, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Berdel, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindel, Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bremer, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwoeppe, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language FACTOR FUSION PROTEINS; TREATMENT RESPONSE; ANTIANGIOGENIC THERAPY; TREATMENT EFFICACY; ANGIOGENESIS; INHIBITION; DELIVERY; GROWTH Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14041