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Monitoring Anti-Angiogenic Therapy in Colorectal Cancer Murine Model using Dynamic Contrast-Enhanced MRI - Comparing Pixel-by-Pixel with Region of Interest Analysis.
MedLine Citation:
PMID:  22905809     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Sorafenib is a multi-kinase inhibitor that blocks cell proliferation and angiogenesis. It is currently approved for advanced hepatocellular and renal cell carcinomas in humans, where its major mechanism of action is thought to be through inhibition of vascular endothelial growth factor and platelet-derived growth factor receptors. The purpose of this study was to determine whether pixel-by-pixel analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is better able to capture the heterogeneous response of Sorafenib in a murine model of colorectal tumor xenografts (as compared with region of interest analysis). MRI was performed on a 9.4T pre-clinical scanner on the initial treatment day. Then either vehicle or drug were gavaged daily (3 days) up to the final image. Four days later, the mice were again imaged. The two-compartment model and reference tissue method of DCE-MRI were used to analyze the data. The results demonstrated that the contrast agent distribution rate constant (K(trans)) were significantly reduced (p < 0.005) at day-4 of Sorafenib treatment. In addition, the K(trans) of nearby muscle was also reduced after Sorafenib treatment. The pixel-by-pixel analysis (compared to region of interest analysis) was better able to capture the heterogeneity of the tumor and the decrease in K(trans) four days after treatment. For both methods, the volume of the extravascular extracellular space did not change significantly after treatment. These results confirm that parameters such as K(trans), could provide a non-invasive biomarker to assess the response to anti-angiogenic therapies such as Sorafenib, but that the heterogeneity of response across a tumor requires a more detailed analysis than has typically been undertaken.
Authors:
C R Haney; X Fan; E Markiewicz; D Mustafi; G S Karczmar; W M Stadler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-10
Journal Detail:
Title:  Technology in cancer research & treatment     Volume:  -     ISSN:  1533-0338     ISO Abbreviation:  Technol. Cancer Res. Treat.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140941     Medline TA:  Technol Cancer Res Treat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Radiology, MC 2026, The University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637. chaney@uchicago.edu.
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