Optical molecular imaging of epidermal growth factor receptor expression to improve detection of oral neoplasia

Neoplasia. 2009 Jun;11(6):542-51. doi: 10.1593/neo.09188.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / chemistry
  • Cyclic AMP / pharmacokinetics
  • Diagnostic Imaging / methods*
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / pharmacokinetics
  • ErbB Receptors / metabolism*
  • Humans
  • Microscopy, Confocal / methods
  • Microscopy, Fluorescence / methods
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity


  • 8-aminohexylamino cAMP
  • Epidermal Growth Factor
  • Cyclic AMP
  • ErbB Receptors