Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW-nimotuzumab
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Wendy Bernhard1,*, Ayman El-Sayed1,*, Kris Barreto1, Carolina Gonzalez1, Wayne Hill1, Angel Casaco Parada2, Humphrey Fonge3,4,5 and C. Ronald Geyer1
1Department of Pathology, University of Saskatchewan, Saskatoon, Canada
2Center for Molecular Immunology, Havana, Cuba
3Department of Medical Imaging, University of Saskatchewan, Saskatoon, Canada
4Department of Medical Imaging, Royal University Hospital, Saskatoon, Canada
5Saskatchewan Centre for Cyclotron Sciences (SCCS), Fedoruk Centre, Saskatoon, Canada
*These authors contributed equally to this work
C. Ronald Geyer, email: [email protected]
Humphrey Fonge, email: [email protected]
Keywords: nimotuzumab; near infrared fluorescence imaging; image-guided surgery; epidermal growth factor receptor; IRDye800CW
Received: August 25, 2017 Accepted: October 27, 2017 Published: December 21, 2017
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies represent an attractive class of image-guided surgical probes because of their high specificity, tumor uptake, and low dissociation from tumor cells that express the antigen. In this study, we developed a NIR fluorescent dye-labeled nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent imaging, and ex vivo biodistribution. There was no difference in binding between nimotuzumab and IRDye800CW-nimotuzumab to EGFR-positive cells. In mice bearing EGFR-positive xenografts, IRDye800CW-nimotuzumab uptake peaked at 4 days post injection and slowly decreased thereafter with high levels of accumulation still observed at 28 days post injection. In EGFR-positive xenografts, IRDye800CW-nimotuzumab showed more than 2-fold higher uptake in tumors compared to IRDye800CW-cetuximab. In addition, liver uptake of IRDye800CW-nimotuzumab was two-fold lower than cetuximab. The lower liver uptake of IRDye800CW-nimotuzumab could have implications on the selected dose for clinical trials of the immunoconjugate. In summary, this study shows that nimotuzumab is a good candidate for NIR fluorescent imaging and image-guided surgery.
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