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Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF-NGR using multi-modal imaging.

Abstract：

:The fusion protein tTF-NGR consists of the extracellular domain of the thrombogenic human tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA (NGR), a ligand of the surface protein CD13 (aminopeptidase N), upregulated on endothelial cells of tumor vessels. tTF-NGR preferentially activates blood coagulation within tumor vasculature, resulting in tumor vessel infarction and subsequent tumor growth retardation/regression. The anti-vascular mechanism of the tTF-NGR therapy approach was verified by quantifying the reduced tumor blood-perfusion with contrast-enhanced ultrasound, the reduced relative tumor blood volume by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging, and by in vivo-evaluation of hemorrhagic bleeding with fluorescent biomarkers (AngioSense(680)) in fluorescence reflectance imaging. The accumulation of tTF-NGR within the tumor was proven by visualizing the distribution of the iodine-123-labelled protein by single-photon emission computed tomography. Use of these multi-modal vascular and molecular imaging tools helped to assess the therapeutic effect even at real time and to detect non-responding tumors directly after the first tTF-NGR treatment. This emphasizes the importance of imaging within clinical studies with tTF-NGR. The imaging techniques as used here have applicability within a wider scope of therapeutic regimes interfering with tumor vasculature. Some even are useful to obtain predictive biosignals in personalized cancer treatment.

journal_name

Angiogenesis

journal_title

Angiogenesis

authors

Persigehl T,Ring J,Bremer C,Heindel W,Holtmeier R,Stypmann J,Claesener M,Hermann S,Schäfers M,Zerbst C,Schliemann C,Mesters RM,Berdel WE,Schwöppe C

doi

10.1007/s10456-013-9391-4

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

235-46

issue

1

eissn

0969-6970

issn

1573-7209

journal_volume

17

pub_type

杂志文章

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