Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging.
In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n=6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal in the tumor correlated significantly with a validated marker of receptor density (P<0.05, r=0.93). Dual-reporter imaging can improve sensitivity and specificity over conventional fluorescence imaging in applications such as fluorescence-guided surgery and directly approximates the receptor status of the tumor, a measure that could be used to inform choices of biological therapies.
Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755, USA. kenneth.tichauer@dartmouth.edu
Kenneth M
KM
Tichauer
Kimberley S
KS
Samkoe
Kristian J
KJ
Sexton
Jason R
JR
Gunn
Tayyaba
T
Hasan
Brian W
BW
Pogue
D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D066246:ErbB Receptors / Q000378:metabolism*; D017930:Genes, Reporter; D006439:Hemodynamics; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology*; D011509:Proteoglycans / Q000737:chemistry; D012372:ROC Curve; D051381:Rats; D013997:Time Factors
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D066246:ErbB Receptors