MRI-coupled fluorescence tomography quantifies EGFR activity in brain tumors.
OBJECTIVE
This report demonstrates the diagnostic potential of magnetic resonance imaging (MRI)-coupled fluorescence molecular tomography (FMT) to determine epidermal growth factor receptor (EGFR) status in brain cancer.


METHODS
Two orthotopic glioma xenograft models were used in this study: one represented high EGFR expression and the other low expression. Nude mice were inoculated with cells from either one of the tumor lines or were used in a sham surgery control group. Animals were imaged using a unique MRI-FMT scanner 48 hours after intravenous injection of a near-infrared fluorophore bound to epidermal growth factor (EGF) ligand. Coronal images of fluorescence activity of the injected dye in the mouse brain were recovered using the MRI images as anatomical templates.


RESULTS
In vivo images of fluorescence activity showed significant differences between animal populations, an observation confirmed by receiver operating characteristic analysis that revealed 100% sensitivity and specificity between animal groups implanted with EGFR((+)) and EGFR((-)) tumor lines. Similar performance was observed between EGFR((+)) and sham surgery control animals.


CONCLUSIONS
This preclinical study suggests that MRI-FMT with fluorescent EGF provides excellent discrimination between tumors based on EGFR status. Reliable quantification of receptor status using minimally invasive techniques would be an important innovation for investigating new and existing cancer treatments that target these cellular mechanisms in research animals, and may be applied to identify receptor amplification in human brain cancer patients. This study represents the first systematic multianimal validation of receptor-specific imaging using MRI-guided fluorescence tomography.
Davis
Scott C
SC
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. Scott.C.Davis@Dartmouth.edu
Samkoe
Kimberley S
KS
O'Hara
Julia A
JA
Gibbs-Strauss
Summer L
SL
Payne
Hannah L
HL
Hoopes
P Jack
PJ
Paulsen
Keith D
KD
Pogue
Brian W
BW
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques; D013382:Subtraction Technique; D014018:Tissue Distribution; D041622:Tomography, Optical / Q000379:methods
D014408:Biomarkers, Tumor; C541485:EGFR protein, mouse; D066246:ErbB Receptors