Optical molecular imaging of epidermal growth factor receptor expression to improve detection of oral neoplasia.
BACKGROUND
The development of noninvasive molecular imaging approaches has the potential to improve management of cancer.


METHODS
In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647) conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined.


RESULTS
The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 microm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging.


CONCLUSIONS
Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.
Nitin
Nitin
N
Southwest Research Institute, San Antonio, TX, USA.
Rosbach
Kelsey J
KJ
El-Naggar
Adel
A
Williams
Michelle
M
Gillenwater
Ann
A
Richards-Kortum
Rebecca R
RR
D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D003952:Diagnostic Imaging / Q000379:methods*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C067297:8-aminohexylamino cAMP; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D066246:ErbB Receptors