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111In-Labeled anti-epidermal growth factor receptor human monoclonal antibody 048-006.


Chopra A.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2012 Oct 10 [updated 2012 Nov 08].


The epidermal growth factor receptor (EGFR) belongs to the ErbB oncogene family and has four subtypes: EGFR (also known as EGFR1), EGFR2, EGFR3, and EGFR4 (1). These receptors mediate their activity through a tyrosine kinase signal transduction pathway (the mechanism of action of the different EGFR receptors is described in brief by Pedersen et al. (2)), are known to promote the proliferation and differentiation of cells, and are involved in the development of several different types of cancers in humans (3). Because EGFR1 is overexpressed in colorectal and head and neck cancers, it is targeted in the clinic with monoclonal antibodies (mAbs) such as cetuximab (a human/mouse chimeric mAb) or panitumumab (a recombinant human mAb) for the treatment of these neoplasms. However, these mAbs cannot be used to treat cancers that bear a mutant KRAS oncogene because this gene is constitutively active and is regulated independently of the EGFR. In addition, immunohistochemical analysis of human tumors that did not harbor a KRAS mutation showed that the efficacy of cetuximab does not always correlate with the level of EGFR expression in the cancerous tissues (4). Also, this technique cannot be used to predict the therapeutic outcome for a patient (5). Therefore, it is important to develop a method that can be used to screen, evaluate, and select patients who can benefit most from the anti-EGFR therapy. Nine human mAb clones that targeted the EGFR were isolated from a phage-display mAb library with an organic solvent method (6). One of the clones, 048-006, was reported to exhibit an in vivo anti-tumor activity against A431 cell xenograft tumors in mice that was comparable to cetuximab. In an effort to develop an imaging agent that can be used to screen for patients who would benefit most from cetuximab (or panitumumab) immunotherapy, the in vitro characteristics of 048-006 were studied with human cell lines, and the biodistribution of 111In-labeled 048-006 ([111In]-048-006) was investigated in nude mice bearing xenograft tumors that expressed different levels of EGFR (5).

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