RGD Reference Report - Perfusion MRI for monitoring the effect of sorafenib on experimental prostate carcinoma: a validation study. - Rat Genome Database

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Perfusion MRI for monitoring the effect of sorafenib on experimental prostate carcinoma: a validation study.

Authors: Cyran, CC  Paprottka, PM  Schwarz, B  Sourbron, S  Ingrisch, M  Von Einem, J  Pietsch, H  Dietrich, O  Hinkel, R  Bruns, CJ  Reiser, MF  Wintersperger, BJ  Nikolaou, K 
Citation: Cyran CC, etal., AJR Am J Roentgenol. 2012 Feb;198(2):384-91.
RGD ID: 6483545
Pubmed: PMID:22268182   (View Abstract at PubMed)
DOI: DOI:10.2214/AJR.11.6951   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate carcinoma  ISOMki67 (Rattus norvegicus)6483545; 6483545 RGD 
prostate carcinoma  IDA 6483545 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mki67  (marker of proliferation Ki-67)

Genes (Mus musculus)
Mki67  (antigen identified by monoclonal antibody Ki 67)

Genes (Homo sapiens)
MKI67  (marker of proliferation Ki-67)


Additional Information