Document Detail


Detecting epidermal growth factor receptor tumor activity in vivo during cetuximab therapy of murine gliomas.
MedLine Citation:
PMID:  19796971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE AND OBJECTIVES: Noninvasive molecular imaging of glioma tumor receptor activity was assessed with diagnostic in vivo fluorescence monitoring during targeted therapy. The study goals were to assess the range of use for treatment monitoring and stratification of tumor types using epidermal growth factor (EGF) receptor (EGFR) status with administration of fluorescently labeled EGF and determine its utility for tumor detection compared to magnetic resonance imaging (MRI).
MATERIALS AND METHODS: EGFR+ and EGFR- glioma tumor lines (human glioma [U251-GFP] and rat gliosarcoma [9L-GFP], respectively) were used to assess these goals, having a 20-fold difference between their EGF uptakes.
RESULTS: Treatment with cetuximab in the EGFR+ tumor-bearing animals led to decreased EGF tumor uptake, whereas for the EGFR- tumors, no change in fluorescence signal followed treatment. This diagnostic difference in EGFR expression could be used to stratify the tumor-bearing animals into groups of potential responders and nonresponders, and receiver-operating characteristic curve analysis revealed an area under the curve (AUC) of 0.92 in separating these tumors. The nonlocalized growth pattern of U251-GFP tumors resulted in detection difficulty on standard MRI, but high EGFR expression made them detectable by fluorescence imaging (AUC = 1.0). The EGFR+ U251-GFP tumor-bearing animals could be noninvasively stratified into treated and untreated groups on the basis of fluorescence intensity difference (P = .035, AUC = 0.90).
CONCLUSIONS: EGFR expression was tracked in vivo with fluorescence and determined to be of use for the stratification of EGFR+ and EGFR- tumors, the detection of EGFR+ tumors, and monitoring of molecular therapy.
Authors:
Summer L Gibbs-Strauss; Kimberley S Samkoe; Julia A O'Hara; Scott C Davis; P Jack Hoopes; Tayyaba Hasan; Brian W Pogue
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-30
Journal Detail:
Title:  Academic radiology     Volume:  17     ISSN:  1878-4046     ISO Abbreviation:  Acad Radiol     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-08     Completed Date:  2010-02-24     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9440159     Medline TA:  Acad Radiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-17     Citation Subset:  IM    
Affiliation:
Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. sgibbs@bidmc.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / administration & dosage*
Brain Neoplasms / diagnosis*,  metabolism*
Cell Line, Tumor
Glioma / diagnosis*,  metabolism*
Humans
Male
Mice
Mice, Nude
Neoplasm Proteins / analysis
Rats
Receptor, Epidermal Growth Factor / metabolism*
Reproducibility of Results
Sensitivity and Specificity
Spectrometry, Fluorescence / methods*
Tumor Markers, Biological / analysis
Grant Support
ID/Acronym/Agency:
P01 CA084203-020003/CA/NCI NIH HHS; P01CA84203/CA/NCI NIH HHS; R01 CA109558-05/CA/NCI NIH HHS; R01CA109558/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Neoplasm Proteins; 0/Tumor Markers, Biological; 0/cetuximab; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor
Comments/Corrections
Comment In:
Acad Radiol. 2010 Jan;17(1):1-2   [PMID:  19969252 ]

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


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