In vivo quantification of tumor receptor binding potential with dual-reporter molecular imaging.
OBJECTIVE
Receptor availability represents a key component of current cancer management. However, no approaches have been adopted to do this clinically, and the current standard of care is invasive tissue biopsy. A dual-reporter methodology capable of quantifying available receptor binding potential of tumors in vivo within a clinically relevant time scale is presented.


METHODS
To test the methodology, a fluorescence imaging-based adaptation was validated against ex vivo and in vitro measures of epidermal growth factor receptor (EGFR) binding potential in four tumor lines in mice, each line expected to express a different level of EGFR.


RESULTS
A strong correlation was observed between in vivo and ex vivo measures of binding potential for all tumor lines (r = 0.99, p < 0.01, slope = 1.80 ± 0.48, and intercept = -0.58 ± 0.84) and between in vivo and in vitro for the three lines expressing the least amount of EGFR (r = 0.99, p < 0.01, slope = 0.64 ± 0.32, and intercept = 0.47 ± 0.51).


CONCLUSIONS
By providing a fast and robust measure of receptor density in tumors, the presented methodology has powerful implications for improving choices in cancer intervention, evaluation, and monitoring, and can be scaled to the clinic with an imaging modality like SPECT.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. Kenneth.Tichauer@dartmouth.edu
Kenneth M
KM
Tichauer
Kimberley S
KS
Samkoe
Kristian J
KJ
Sexton
Shannon K
SK
Hextrum
Harold H
HH
Yang
W Spencer
WS
Klubben
Jason R
JR
Gunn
Tayyaba
T
Hasan
Brian W
BW
Pogue
D000818:Animals; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results
D015335:Molecular Probes; D066246:ErbB Receptors