In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies.

Abstract

PURPOSE:

Epidermal growth factor receptors (EGFR) play an important role in tumorigenesis and, therefore, have become targets for new molecular therapies. Here, we use a "cocktail" of optically labeled monoclonal antibodies directed against EGFR-1 (HER1) and EGFR-2 (HER2) to distinguish tumors by their cell surface expression profiles.

EXPERIMENTAL DESIGN:

In vivo imaging experiments were done in tumor-bearing mice following s.c. injection of A431 (overexpressing HER1), NIH3T3/HER2+ (overexpressing HER2), and Balb3T3/DsRed (non-expression control) cell lines. After tumor establishment, a cocktail of optically labeled antibodies: Cy5.5-labeled cetuximab (anti-HER1) and Cy7-labeled trastuzumab (anti-HER2) was i.v. injected. In vivo and ex vivo fluorescence imaging was done. For comparison with radionuclide imaging, experiments were undertaken using (111)Indium-labeled antibodies. Additionally, a "blinded" diagnostic study was done for mice bearing one tumor type.

RESULTS:

In vivo spectral fluorescent molecular imaging of 14 mice with three tumor types clearly differentiated tumors using the cocktail of optically labeled antibodies both in vivo and ex vivo. Twenty-four hours after injection, A431 and NIH3T3/HER2+ tumors were detected distinctly by their peak on Cy5.5 and Cy7 spectral images, respectively; radionuclide imaging was unable to clearly distinguish tumors at this time point. In blinded single tumor experiments, investigators were able to correctly diagnose a total of 40 tumors.

CONCLUSION:

An in vivo imaging technique using an antibody cocktail simultaneously differentiated two tumors expressing distinct EGFRs and enabled an accurate characterization of each subtype.

• Authors: Tristan Barrett, Yoshinori Koyama, Yukihiro Hama, Gregory Ravizzini, In Soo Shin, Beom-Su Jang, Chang H Paik, Yasuteru Urano, Peter L Choyke, Hisataka Kobayashi
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 22 Pt 1 Pg. 6639-48 (Nov 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17982120 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CY5.5 cyanine dye
• Carbocyanines
• Molecular Probes
• indotricarbocyanine
• EGFR protein, human
• ErbB Receptors
• Receptor, ErbB-2
• Trastuzumab
• Cetuximab

Topics

• Animals
• Antibodies, Monoclonal (chemistry)
• Antibodies, Monoclonal, Humanized
• Carbocyanines (analysis, chemistry)
• Cell Line, Tumor
• Cetuximab
• ErbB Receptors (analysis)
• Flow Cytometry
• Mice
• Mice, Inbred Strains
• Molecular Probes (analysis, chemistry)
• Neoplasms (diagnosis, diagnostic imaging)
• Radionuclide Imaging
• Receptor, ErbB-2 (analysis)
• Trastuzumab