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

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

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

Rabea Hinkel MD, Abstract Co-Author: Nothing to Disclose

To investigate the effects of Sorafenib on experimental prostate carcinomas using functional parameters of tumor microcirculation quantified by dynamic contrast-enhanced (DCE-) MRI with immunohistochemical validation.

Copenhagen rats (n=20) implanted with subcutaneous prostate carcinomas (MLLB-2) were imaged on day0 and day7 using DCE-MRI at 3T enhanced with Gadobutrol. The treatment group (n=10) received daily applications of 10mg/kg bodyweight Sorafenib. Quantitative measurements of tumor perfusion (ml/100ml/min), vascularity (%) and permeability-surface area product (ml/100ml/min) were calculated based on a 2-compartment kinetic model. Tumors were excised on day7 to undergo immunohistochemical staining for tumor vascularity (RECA-1), proliferation (Ki-67) and apoptosis (TUNEL).

Tumor perfusion in Sorafenib-treated prostate carcinomas declined significantly from day0 to day7 (47.9±36.8 vs. 24.4±18.6ml/100ml/min, p0.05). Tumor vascularity decreased significantly under Sorafenib treatment from day0 to day7 (15.6±11.4 to 5.4±2.1%, p<0.05) with no significant change noted in the control group (12.9±3.3 to 10.3±7.3%). Immunohistochemistry revealed significantly lower tumor vascularity in the therapy than in the control group (RECA-1 74.4 ±16.9 vs. 197±75.4, p<0.05). In Sorafenib-treated tumors, significantly more apoptotic cells (TUNEL 6,923±3,761 vs. 3,167±1,500, p<0.05) and significantly less proliferating cells (Ki-67 10,198±3,064 vs. 15,003±3,674, p<0.05) were observed than in the control group. Modest but significant (p<0.05) correlations were observed between tumor perfusion and TUNEL (r=-0.56) as well as RECA-1 (r=0.56) stainings.

Tumor perfusion quantified by DCE-MRI can be applied as non-invasive surrogate parameter for monitoring the anti-angiogenic, anti-proliferative and pro-apoptotic effects of Sorafenib on prostate carcinomas as validated by immunohistochemistry. Modest but significant correlations were observed between tumor perfusion and immunohistochemical tumor cell apoptosis as well as tumor vascularity.

DCE-MRI can be applied to generate functional parameters of tumor microcirculation to monitor anti-angiogenic, anti-proliferative and pro-apoptotic effects of Sorafenib on prostate carcinomas in rats.

Cyran, C, Paprottka, P, Schwarz, B, Reiser, M, Wintersperger, B, Nikolaou, K, Von Einem, J, Sourbron, S, Ingrisch, M, Dietrich, O, Hinkel, R, Dynamic Contrast-enhanced (DCE)-MRI with Gadobutrol for Monitoring Sorafenib Effect on Experimental Prostate Carcinomas: 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/2011/11034196.html