title: In vivo monitoring of sorafenib therapy effects on experimental prostate carcinomas using dynamic contrast-enhanced MRI and macromolecular contrast media.
abstract: OBJECTIVE
  To investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with macromolecular contrast media (MMCM) to monitor the effects of the multikinase inhibitor sorafenib on subcutaneous prostate carcinomas in rats with immunohistochemical validation.
  
  
  METHODS
  Copenhagen rats, implanted with prostate carcinoma allografts, were randomized to the treatment group (n = 8) or the control group (n = 8). DCE-MRI with albumin-(Gd-DTPA)35 was performed at baseline and after 1 week using a clinical 3-Tesla system. The treatment group received sorafenib, 10 mg/kg body weight daily. Kinetic analysis yielded quantitative parameters of tumor endothelial permeability-surface area product (PS; ml/100 ml/min) and fractional blood volume (Vb, %). Tumors were harvested on day 7 for immunohistochemical analysis.
  
  
  RESULTS
  In sorafenib-treated tumors, PS (0.62 ± 0.20 vs 0.08 ± 0.09 ml/100 ml/min; P < 0.01) and Vb (5.1 ± 1.0 vs 0.56 ± 0.48%; P < 0.01) decreased significantly from day 0 to day 7. PS showed a highly significant inverse correlation with tumor cell apoptosis (TUNEL; r = -0.85, P < 0.001). Good, significant correlations of PS were also observed with tumor cell proliferation (Ki-67; r = 0.67, P < 0.01) and tumor vascularity (RECA-1; r = 0.72, P < 0.01). MRI-assayed fractional blood volume Vb showed a highly significant correlation with tumor vascularity (RECA-1; r = 0.87, P < 0.001) and tumor cell proliferation (Ki-67; r = 0.82, P < 0.01).
  
  
  CONCLUSIONS
  Results of DCE-MRI with MMCM demonstrated good, significant correlations with the immunohistochemically assessed antiangiogenic, antiproliferative, and proapoptotic effects of a 1-week, daily treatment course of sorafenib on experimental prostate carcinoma allografts.
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany; C.C. Cyran and B. Schwarz contributed equally to this research project, and share first authorship.
authors.forename: Clemens C
authors.initials: CC
authors.lastname: Cyran
authors.affiliation: Department of Surgery, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany; C.C. Cyran and B. Schwarz contributed equally to this research project, and share first authorship.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schwarz
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Paprottka
authors.affiliation: Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany; Division of Medical Physics, University of Leeds, Leeds, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Sourbron
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Jobst C
authors.initials: JC
authors.lastname: von Einem
authors.affiliation: Josef Lissner Laboratory for Biomedical Imaging, Department of Clinical Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dietrich
authors.affiliation: Department of Cardiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Rabea
authors.initials: R
authors.lastname: Hinkel
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Clevert
authors.affiliation: Department of Surgery, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Maximilian F
authors.initials: MF
authors.lastname: Reiser
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Nikolaou
authors.affiliation: Department of Clinical Radiology, Laboratory for Experimental Radiology, University of Munich Hospitals - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377 Munich, Germany; Department of Medical Imaging, University Health Network, University of Toronto, 585 University Avenue, Toronto ON M5G 2N2, Canada.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Wintersperger
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003287:Contrast Media; D007089:Image Enhancement; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D000077157:Sorafenib; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor