Clemens Christian Joachim Cyran MD, Presenter: Research grant, Bayer AG

Philipp Paprottka, Abstract Co-Author: Nothing to Disclose

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

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

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

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

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

Michael Ingrisch, Abstract Co-Author: Nothing to Disclose

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

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

To investigate DCE-CT for monitoring the effects of the tyrosine kinase inhibitor sorafenib on experimental prostate carcinomas in rats by quantitative measurements of functional parameters of tumor microcirculation with immunohistochemical validation.

Prostate carcinoma allografts (MLLB-2) implanted subcutaneously in male Copenhagen rats (n=16) were imaged at baseline and after a one-week treatment course of Sorafenib by DCE-CT (200mAs, 80kv, TA=90s) with Iopromide. The treatment group (n=8) received daily applications of Sorafenib (10mg/kg bodyweight). Quantitative parameters of tumor perfusion (ml/100ml/min), tumor vascularity (%) and extraction flow (ml/100ml/min) were calculated using a 2-compartment kinetic uptake model. Functional DCE-CT parameters were correlated with immunohistochemistry.

Sorafenib significantly suppressed tumor perfusion (25.1±9.8 to 9.5±6.0ml/100ml/min, p<0.05), tumor vascularity (15.6 ± 11.4 to 5.4±2.1%; p<0.01) and extraction flow (8.7±4.5 to 2.7±2.5ml/100ml/min; p<0.01) in prostate carcinoma allografts over the treatment course of one week. Immunohistochemistry revealed significantly lower tumor vascularity in the therapy than in the control group (RECA-1 176.9 ±22.3 vs. 298.9±48.0, p<0.05). In Sorafenib-treated tumors, significantly more apoptotic cells (TUNEL 6,976±3,303 vs. 3,722±1,445, p<0.05) and significantly less proliferating cells (Ki-67 7,605±3,120 vs. 17,557±1446, p<0.05) were observed than in the control group. DCE-CT tumor perfusion correlated significantly with immunohistochemical tumor vascularity (RECA-1; r=0.43, p<0.05), tumor cell proliferation (Ki-67, r = 0.53, p<0.05) and tumor cell apoptosis (TUNEL; r=-0,54, p<0.05). DCE-CT tumor vascularity correlated significantly with immunohistochemical tumor cell apoptosis (TUNEL; r=-0.51, p<0.05), tumor cell proliferation (Ki-67; r=0.68, p<0.01) and tumor vascularity (RECA-1; r=0.41, p<0.05).

Sorafenib significantly suppressed tumor perfusion, tumor vascularity and extraction flow quantified by DCE-CT in experimental prostate carcinomas in rats with significant correlations to the anti-angiogenic, anti-proliferative and pro-apoptotic effects observed by immunohistochemistry.

Quantitative parameters of tumor microcirculation assayed by DCE-CT may be applicable as non-invasive imaging biomarkers of prostate carcinoma therapy response to Sorafenib.

Cyran, C, Paprottka, P, Schwarz, B, Reiser, M, Wintersperger, B, Nikolaou, K, Sourbron, S, Ingrisch, M, Dietrich, O, Bruns, C, Dynamic, Contrast-enhanced (DCE-) CT Imaging Biomarkers for Monitoring Sorafenib Effect on Experimental Prostate Carcinomas in Rats: A Validation Study.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11001383.html