Philipp Paprottka, Presenter: Nothing to Disclose

Clemens Christian Joachim Cyran MD, Abstract Co-Author: Research grant, Bayer AG

Bettina Schwarz MD, Abstract Co-Author: Nothing to Disclose

Steven Sourbron PhD, Abstract Co-Author: Nothing to Disclose

Olaf Dietrich PhD, Abstract Co-Author: Nothing to Disclose

Konstantin Nikolaou MD, Abstract Co-Author: Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group Speakers Bureau, Bayer AG

Christiane J Bruns MD, PhD, Abstract Co-Author: Nothing to Disclose

Jobst Von Einem, Abstract Co-Author: Nothing to Disclose

Bernd J. Wintersperger MD, Abstract Co-Author: Speakers Bureau, Bayer AG Speakers Bureau, Siemens AG

Maximilian F. Reiser MD, Abstract Co-Author: Nothing to Disclose

To investigate the effects of the multikinase inhibitor Sorafenib on subcutaneous prostate carcinomas in rats using dynamic, contrast-enhanced (DCE-) MRI with immunohistochemical validation.

Copenhagen rats, implanted with prostate carcinoma allografts (MLLB-2) were randomized to the treatment (n=8) or the control group (n=8). DCE-MRI enhanced with albumin-(Gd-DTPA)35 was performed at baseline and after one week. The treatment group received daily applications of Sorafenib (10mg/kg bodyweight). Kinetic analysis of signal intensity data yielded quantitative parameters of tumour endothelial permeability-surface area product (PS; ml/100ml/min) and tumour blood volume (Vb, %). Tumours were harvested on day 7 for immunohistochemical analysis of tumour vascularity, tumour cell proliferation and apoptosis.

In Sorafenib-treated tumours (n=8), PS (0.62±0.20 vs. 0.08±0.09ml/100ml/min; p<0.01) and Vb (5.1±1.0 vs. 0.56±0.48; p<0.01) decreased significantly from day0 to day7. Correspondingly, immunohistochemistry revealed significantly lower tumour vascularity in the therapy than in the control group (RECA-1 5.1±1.9 vs. 23.1±7.7, p<0.05). In Sorafenib-treated tumours, significantly more apoptotic cells (TUNEL 427±283 vs. 218±312, p<0.05) and significantly less proliferating cells (Ki-67 847±307 vs. 1692±469, p<0.05) were observed than in the control group.

In conclusion, a one-week treatment course of Sorafenib significantly inhibited tumour endothelial permeability and tumour vascularity in experimental prostate carcinomas quantified by DCE-MRI. Immunohistochemistry revealed corresponding anti-angiogenic, anti-proliferative and pro-apoptotic effects of Sorafenib in good correlation with non-invasive DCE-MRI.

DCE-MRI may become a reliable technique for monitoring early therapy response of tumours to anti-angiogenic therapy.

Paprottka, P, Cyran, C, Schwarz, B, Sourbron, S, Dietrich, O, Nikolaou, K, Bruns, C, Von Einem, J, Wintersperger, B, Reiser, M, In Vivo Monitoring of Sorafenib Therapy Effects on Experimental Prostate Carcinomas Using Dynamic Contrast-enhanced MRI with Immunohistochemical Correlations.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11005144.html