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Interstitial fluid pressure and associated lymph node metastasis revealed in tumors by dynamic contrast-enhanced MRI.
MedLine Citation:
PMID:  23027087     Owner:  NLM     Status:  In-Data-Review    
Elevated interstitial fluid pressure (IFP) in tumors can cause metastatic dissemination and treatment resistance, but its study poses a challenge because of a paucity of noninvasive imaging strategies. In this study, we address this issue by reporting the development of a noninvasive tool to assess tumor IFP and interstitial hypertension-induced lymph node metastasis. Using mouse xenograft models of several types of human cancer, we used gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as a contrast agent for dynamic contrast-enhanced MRI (DCE-MRI). Immediately after Gd-DTPA administration, a high-signal-intensity rim was observed in the tumor periphery, which moved outward with time. Assuming the velocity of Gd-DTPA to be equal to the fluid flow velocity, we used a simple model of peritumoral interstitial fluid flow to calculate the fluid flow velocity at the tumor surface (v(0)) based on the rim movement. Significant positive correlations were found between v(0) and IFP in all tumor xenografts. Moreover, the primary tumors of metastasis-positive mice displayed higher IFP and v(0) than the primary tumors of metastasis-negative mice. Findings were confirmed in cervical cancer patients with pelvic lymph node metastases, where we found v(0) to be higher compared with patients without lymph node involvement (P < 0.00001). Together, these findings establish that Gd-DTPA-based DCE-MRI can noninvasively visualize tumor IFP, and they reveal the potential for v(0) determined by this method to serve as a novel general biomarker of tumor aggressiveness. Cancer Res; 72(19); 4899-908. ©2012 AACR.
Tord Hompland; Christine Ellingsen; Kirsti Marie Ovrebø; Einar K Rofstad
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  72     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4899-908     Citation Subset:  IM    
Authors' Affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
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