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- W2412297658 abstract "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 G1 (IgG1) monoclonal antibody (mAb) against the extracellular domain of recombinant HER2 (11), was labeled as 111In-trastuzumab (12-14). C225, an anti-EGFR (HER1), mouse-human chimeric, IgG1 mAb, also known as erbitux and cetuximab, was labeled as 99mTc-EC-C225 (15, 16) for imaging EGFR expression on solid tumors with the use of single-photon emission computed tomography (SPECT). However, the pharmacokinetics of the intact radiolabeled mAb, with high liver uptake and slow blood elimination, are generally not ideal for imaging (17, 18). Smaller antibody fragments, such as scFv, Fab, or F(ab')2, have better imaging pharmacokinetics because they are rapidly excreted by the kidneys. Nanobodies are the smallest intact antigen-binding fragments (15 kDa) isolated from heavy-chain camelid antibodies, and they exhibit efficient and specific tumor targeting (19-21). Nanobody 7D12 was labeled with 99mTc at its C-terminus hexahistidine tail as a SPECT agent for imaging EGFR expression in tumors in mice (22). For use with positron emission tomography (PET), nanobody 7D12 was conjugated with the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) and labeled with 68Ga (t1/2, 67.7 min) to form 68Ga-Df-Bz-NCS-7D12 for imaging HER1 expression in tumors (23)." @default.
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- W2412297658 date "2012-06-07" @default.
- W2412297658 modified "2023-09-23" @default.
- W2412297658 title "68Ga-Desferrioxamine p-isothiocyanatobenzyl-anti-EGFR nanobody 7D12" @default.
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