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• W2399851803 abstract "The hepatocyte growth factor (HGF) is the only known ligand of the mesenchymal-epithelial transition factor (c-Met) (also known as the HGF receptor) that has an important function, including cell development, proliferation, scattering, migration, and angiogenesis, all of which are necessary for the survival and repair of tissues (1). c-Met is known to mediate its activity through an intracellular tyrosine kinase (TK) that activates different signal transduction pathways, leading to initiation of the various cell processes (2). Also, deregulation of c-Met activity due to paracrine/autocrine activation, overexpression, or a mutation promotes the development of a neoplastic cell phenotype (2). Overexpression of c-Met and HGF has been associated with a poor prognosis and survival of the patient (3), suggesting that the c-Met receptor may be a suitable target for the detection of cancers at an early stage, which could help in the development of an appropriate treatment regimen to improve patient prognosis (4). c-Met is the target of several drugs under evaluation in clinical trials approved by the United States Food and Drug Administration. Investigators recently generated a monoclonal antibody (mAb) that inhibits the HGF–c-Met interaction and identified the active mAb epitope peptide as KSLSRHDHIHHH, which was designated as the c-Met binding peptide (cMBP) (5). The cMBP and its derivatives (containing either a tri-amino acid linker, Gly-Gly-Gly (GGG), or an aliphatic carbon linker, 8-aminooctanoic acid (AOC)) were labeled with 125I to generate 125I-cMBP, 125I-cMBP-GGG, and 125I-cMBP-AOC, and these agents were used to detect c-Met TK-positive tumor xenografts in mice (6). From this study the investigators concluded that although 125I-cMBP-GGG was a suitable imaging agent for the c-Met–positive tumors, the imaging signal could probably be improved by either changing the linker or by using a different nuclide or source of signal (such as an optical imaging agent).In an attempt to generate a c-Met–positive tumor imaging agent superior to the 125I- cMBP-GGG, investigators conjugated a near-infrared (NIR) fluorescent dye, cyanine 5.5 (Cy5.5), to cMBP-GGG and cMBP-AOC to obtain cMBP-GGG-Cy5.5 and cMBP-AOC-Cy5.5 (4). The Cy5.5-conjugated cMBP derivatives were then evaluated for the NIR imaging of c-Met–positive xenograft tumors in a mouse model. This chapter describes the characterization of only cMBP-GGG-Cy5.5. The other c-Met imaging agents (125I-cMBP, 125I-cMBP-GGG, 125I-cMBP-AOC, and cMBP-AOC-Cy5.5) are described in separate MICAD chapters (7-10)." @default.
• W2399851803 created "2016-06-24" @default.
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• W2399851803 date "2009-09-10" @default.
• W2399851803 modified "2023-09-27" @default.
• W2399851803 title "Mesenchymal-epithelial transition factor binding peptide-Gly-Gly-Gly conjugated to Cy5.5" @default.
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