Y-CHX-A''-Diethylenetriamine pentaacetic acid-cetuximab

Epidermal growth factor (EGF) is a 53-amino acid cytokine (6.2 kDa) that is secreted by ectodermic cells, monocytes, kidneys, and duodenal glands (1). EGF stimulates growth of epidermal and epithelial cells. EGF and at least seven other growth factors and their transmembrane receptor kinases play important roles in cell proliferation, survival, adhesion, migration, and differentiation. The EGF receptor (EGFR) family consists of four transmembrane receptors, including EGFR (HER1/erbB-1), HER2 (erbB-2/neu), HER3 (erbB-3), and HER4 (erbB-4) (2). HER1, HER3, and HER4 comprise three major functional domains: an extracellular ligand-binding domain, a hydrophobic transmembrane domain, and a cytoplasmic tyrosine kinase domain. No ligand has been clearly identified for HER2; however, HER2 can be activated as a result of ligand binding to other HER receptors with the formation of receptor homodimers and/or heterodimers (3). HER1 as well as HER2 are overexpressed on many solid tumor cells such as breast, non–small-cell lung, head and neck, and colon cancers (4-6). The high levels of HER1 and HER2 expression on cancer cells are associated with a poor prognosis (7-10). Trastuzumab, a humanized immunoglobulin G (IgG) monoclonal antibody against the extracellular domain of recombinant HER2 (11), was labeled as In-trastuzumab (12-14). C225, an anti-EGFR (HER1), mouse-human chimeric, monoclonal IgG antibody, also known as erbitux and cetuximab, was labeled as Tc-EC-C225 (15, 16) for imaging EGFR expression on solid tumors using single-photon emission computed tomography (SPECT). For evaluation as a positron emission tomography (PET) imaging agent for EGFR, Y has been attached to cetuximab CHX-A''-diethylenetriamine pentaacetic acid (CHX-A''-DTPA) to form Y-CHX-A''-DTPA-cetuximab (17).