In vivo molecular imaging to diagnose and subtype tumors through receptor-targeted optically labeled monoclonal...

Area of Science:

• Biomedical optics
• Molecular imaging
• Cancer diagnostics

Background:

• Cell surface receptor expression profiles can differentiate tumor types.
• Noninvasive molecular imaging offers potential for early cancer diagnosis.

Purpose of the Study:

• To develop and validate a multifilter spectrally resolved optical imaging technique for simultaneous, noninvasive differentiation of multiple tumor types based on distinct cell surface receptor expression.
• To assess the efficacy of using three fluorescently labeled antibodies targeting different receptors (EGFR subtypes and IL-2Ralpha) for in vivo tumor discrimination.

Main Methods:

• Utilized multifilter spectrally resolved optical imaging with three fluorescently labeled monoclonal antibodies (cetuximab-Cy5, trastuzumab-Cy7, daclizumab-AlexaFluor-700) targeting HER-1, HER-2, and IL-2Ralpha receptors, respectively.
• Administered a cocktail of these antibodies to mice bearing distinct tumor models (A431, NIH3T3/HER2(+), SP2/Tac) and performed optical fluorescence imaging after 24 hours using multiple filter sets (yellow, red, deep red).

Main Results:

• Spectrally resolved imaging successfully distinguished between the three tumor types based on their unique optical spectra.
• Employing three-filter sets significantly enhanced the signal-to-background ratio compared to a single-filter set by reducing background noise (P < .022).
• Improved signal-to-noise ratio facilitated better differentiation of the targeted receptors and their respective tumors.

Conclusions:

• Multifilter spectrally resolved optical imaging enables simultaneous in vivo diagnosis and differentiation of multiple tumor types.
• The use of multiple filter sets substantially reduces background signal, increasing the signal-to-noise ratio and potentially allowing resolution of more optical dyes within the near-infrared spectrum.