Document Detail


Molecular imaging of fibrin in a breast cancer xenograft mouse model.
MedLine Citation:
PMID:  22960948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE AND OBJECTIVES: Fibrin deposition has been indicated within the stroma of a majority of solid tumors. Here we assess the feasibility of using the established fibrin-specific probe EP-2104R for noninvasive imaging of fibrin in the context of breast cancer.
METHODS: EP-2104R, untargeted gadopentetate dimeglumine (Gd-DTPA), and a newly synthesized nonfibrin binding control linear peptide (CLP) were compared using steady-state and dynamic contrast-enhanced magnetic resonance imaging in a breast cancer xenograft mouse model at 9.4 T.
RESULTS: EP-2104R transiently enhanced both tumor core and tumor periphery, but only the enhancement in the tumor periphery persisted even 90 minutes after EP-2104R administration. However, untargeted Gd-DTPA and CLP are not retained in the tumor periphery. The half-life of EP-2104R in the tumor periphery (103 ± 18 minutes) is significantly longer (P < 0.05) than that of either Gd-DTPA (29.6 ± 2.4 minutes) or CLP (42.4 ± 1.5 minutes), but the rate of clearance is similar for all the 3 probes from the tumor core. The presence of high concentrations of fibrin in the tumor periphery was corroborated using immunohistochemistry with a fibrin-specific antibody.
CONCLUSIONS: The persistent enhancement observed in the tumor periphery with EP-2104R is likely a result of its fibrin-specific binding rather than its size and demonstrates the feasibility of EP-2104R for molecular imaging of fibrin in tumor stroma.
Authors:
Ritika Uppal; Zdravka Medarova; Christian T Farrar; Guangping Dai; Anna Moore; Peter Caravan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Investigative radiology     Volume:  47     ISSN:  1536-0210     ISO Abbreviation:  Invest Radiol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2013-02-06     Revised Date:  2013-05-15    
Medline Journal Info:
Nlm Unique ID:  0045377     Medline TA:  Invest Radiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-8     Citation Subset:  IM    
Affiliation:
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / diagnosis,  pathology
Animals
Breast Neoplasms / diagnosis*,  pathology
Disease Models, Animal
Feasibility Studies
Female
Fibrin*
Gadolinium / diagnostic use*
Gadolinium DTPA / diagnostic use*
Mice
Molecular Imaging*
Peptides / diagnostic use*
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
P41RR14075/RR/NCRR NIH HHS; R01 EB009062/EB/NIBIB NIH HHS; R01 HL109448/HL/NHLBI NIH HHS; R01EB009062/EB/NIBIB NIH HHS; R01HL109448/HL/NHLBI NIH HHS; S10RR025563/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/EP-2104R; 0/Peptides; 7440-54-2/Gadolinium; 80529-93-7/Gadolinium DTPA; 9001-31-4/Fibrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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