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127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

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Dynamic contrast-enhanced MRI monitoring proofs inhibition of tumor growth and angiogenesis in experimental prostate carcinomas by sorafenib

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  • E. Bettina Schwarz - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München, Deutschland
  • Clemens C. Cyran - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München, Deutschland
  • Philipp Paprottka - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Steven Sourbron - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Jobst von Einem - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Rabea Hinkel - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Bernd J. Wintersberger - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Konstantin Nikolau - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Maximilian F. Reiser - Universitätsklinikum der LMU, München-Großhadern, Institut für klinische Radiologie, München, Deutschland
  • Christiane J. Bruns - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München, Deutschland

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch246

doi: 10.3205/10dgch246, urn:nbn:de:0183-10dgch2462

Published: May 17, 2010

© 2010 Schwarz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: The oral multikinase inhibitor sorafenib has been approved for the treatment of advanced HCC and metastatic RCC. Up to now, there is no data on its potential anti-angiogenic and anti-proliferative effects on other tumor entities. Our aim was to investigate the anti-angiogenic effects of sorafenib on experimental prostate carcinomas in rats by dynamic contrast-enhanced MRI assays of endothelial permeability and tumor vascularity.

Materials and methods: 16 Copenhagen rats were implanted with s.c. prostate carcinoma allografts (6*106 MLLB-2 cells in matrigel). The animals were imaged at baseline and after a one-week treatment course of sorafenib via gavage by dynamic MRI at 3.0T following enhancement with the macromolecular contrast agent albumin-(Gd-DTPA). Quantitative MRI estimates of tumor microvessel permeability (transfer constant, 10-3 min-1) and tumor vascular richness (blood volume; %) were calculated based on a 2-compartment kinetic model. ICH stainings for HE, CD31, RECA-1, Ki67 and TUNEL were done.

Results: Endothelial permeability and blood volume in the tumors was significantly suppressed by Sorafenib over the treatment course of one week. The transfer constant in sorafenib-treated tumors (n=8) yielded a significant decrease in endothelial permeability from baseline to day 7 (TCbaseline= 0.62 ± 0.20 to TCday7=0.08 ± 0.09; p<0.01). The blood volume in sorafenib-treated tumors decreased significantly over the treatment course (BV baseline= 5.1 ± 1.0 to BV day7= 0.56 ± 0.48; p<0.01).

Conclusion: Sorafenib significantly reduced endothelial permeability and tumor vascularity in our model as assayed by dynamic MRI enhanced with macromolecular contrast media. Results indicate a significant anti-angiogenic and anti-proliferative effect of sorafenib in our model. Dynamic MRI enhanced with macromolecular contrast media could prove valuable for monitoring the anti-angiogenic effects of this adjuvant chemotherapy on an individual patient basis.