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Perfusion MRI for monitoring the effect of sorafenib on experimental prostate carcinoma: a validation study.
MedLine Citation:
PMID:  22268182     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVE: The purpose of this study was to investigate with immunohistochemical validation whether dynamic contrast-enhanced MRI with small-molecule contrast medium is useful for monitoring the effects of the multikinase inhibitor sorafenib on prostate carcinomas in rats.
MATERIALS AND METHODS: Copenhagen rats (n = 20) into which prostate carcinoma (MAT-Ly-Lu-B2) had been implanted subcutaneously were imaged on the day of implantation and 7 days later with 3-T dynamic gadobutrol-enhanced MRI. The therapy group (n = 10) received daily administration of 10 mg/kg body weight sorafenib. Quantitative measurements of tumor perfusion, tumor vascularity, and permeability-surface area product were calculated with a two-compartment model. Dynamic contrast-enhanced MRI values were correlated with immunohistochemical results for validation.
RESULTS: Tumor perfusion in sorafenib-treated prostate carcinoma declined significantly from day 0 to day 7 (47.9 ± 36.8 mL/100 mL/min to 24.4 ± 18.6 mL/100 mL/min; p < 0.05). No significant effect on permeability-surface area product was observed in either the therapy or the control group (p > 0.05). Tumor vascularity decreased significantly (p < 0.05) from day 0 to day 7 under sorafenib treatment (15.6% ± 11.4% to 5.4% ± 2.1%). Immunohistochemical analysis revealed significantly lower tumor vascularity in the therapy than in the control group (rat endothelial cell antigen 1, 74.4 ± 16.9 cells vs 197 ± 75.4 cells; p < 0.05). In sorafenib-treated tumors, significantly more apoptotic cells (terminal deoxynucleotidyl transferase-mediated nick end labeling, 6923 ± 3761 vs 3167 ± 1500; p < 0.05) and significantly fewer proliferating cells (Ki-67, 10,198 ± 3064 vs 15,003 ± 3674; p < 0.05) were observed than in the control group. Modest but significant correlations were observed between tumor perfusion and immunohistochemical tumor cell apoptosis (r = -0.56; p < 0.05) and between tumor perfusion and immunohistochemical tumor vascularity (r = 0.56; p < 0.05).
CONCLUSION: Tumor perfusion quantified with gadobutrol-enhanced dynamic contrast-enhanced MRI can be used as a noninvasive surrogate parameter for monitoring the antiangiogenic, antiproliferative, and proapoptotic effects of sorafenib on prostate carcinoma allografts as validated with immunohistochemical analysis.
Authors:
Clemens C Cyran; Philipp M Paprottka; Bettina Schwarz; Steven Sourbron; Michael Ingrisch; Jobst von Einem; Hubertus Pietsch; Olaf Dietrich; Rabea Hinkel; Christiane J Bruns; Maximilian F Reiser; Bernd J Wintersperger; Konstantin Nikolaou
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  AJR. American journal of roentgenology     Volume:  198     ISSN:  1546-3141     ISO Abbreviation:  AJR Am J Roentgenol     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7708173     Medline TA:  AJR Am J Roentgenol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  384-91     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Radiology, Center for Experimental Radiology, University Hospitals Munich, Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
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