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99mTc-Hydrazinonicotinamide-chitosan-anti-vascular endothelial growth factor receptor 2 monoclonal antibody DC101.

Authors

Leung K.

Source

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2009 Sep 15 [updated 2009 Dec 24].

Excerpt

Vascular endothelial growth factor (VEGF) consists of at least six isoforms with various numbers of amino acids (121, 145, 165, 183, 189, and 206 amino acids) produced through alternative splicing (1). VEGF121, VEGF165, and VEGF189 are the forms secreted by most cell types and are active as homodimers linked by disulfide bonds. VEGF121 does not bind to heparin like the other VEGF species (2). VEGF is a potent angiogenic factor that induces proliferation, sprouting, migration, and tube formation of endothelial cells. There are three high-affinity tyrosine kinase VEGF receptors (VEGFRs) on endothelial cells (VEGFR-1, Flt-1; VEGFR-2, KDR/Flt-1; and VEGFR-3, Flt-4). Several types of non-endothelial cells such as hematopoietic stem cells, melanoma cells, monocytes, osteoblasts, and pancreatic β cells also express VEGFRs (1). VEGFRs have been found to be overexpressed in various tumor cells and tumor-associated endothelial cells (3). Inhibition of VEGFR function has been shown to inhibit pathological angiogenesis as well as tumor growth and metastasis (4, 5). Radiolabeled VEGF has been developed as a tracer for imaging solid tumors and angiogenesis in humans (6-8). Chitosan is a linear polysaccharide composed of D-glucosamine and N-acetylglucosamine subunits with numerous amine groups in D-glucosamine for ligand conjugation. A rat anti-VEGFR-2 monoclonal antibody (mAb), DC101, has been shown to inhibit angiogenesis with suppression of tumor growth and metastasis. Lee et al. (9) conjugated DC101 mAb to hydrazinonicotinamide (HYNIC)-chitosan for radiolabeling with 99mTc to form 99mTc-HYNIC-chitosan-DC101 for imaging VEGFR-2 expression under ischemic conditions.

PMID:
20641647
[PubMed]
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