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Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW-nimotuzumab

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 t...

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Detalles Bibliográficos
Autores principales: Bernhard, Wendy, El-Sayed, Ayman, Barreto, Kris, Gonzalez, Carolina, Hill, Wayne, Parada, Angel Casaco, Fonge, Humphrey, Geyer, C. Ronald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814206/
https://www.ncbi.nlm.nih.gov/pubmed/29464066
http://dx.doi.org/10.18632/oncotarget.23557
Descripción
Sumario: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.