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• W160248964 abstract "Colorectal cancer (CRC) is the second most common neoplastic condition detected in the men and women of the United States. In 2008 it is estimated that ~150,000 individuals will be diagnosed with this disease and that it will result in the death of nearly one third of the patients (1). Most of the patients who have this cancer die because it metastasizes to the liver, and early screening of the neoplasm would help devise a suitable and favorable treatment for the patient (2). The United States Food and Drug Administration has approved radioimmunoscintigraphic agents that are based on monoclonal antibodies for the imaging of colorectal cancers, but these agents have limitations because of incomplete penetration in tumors as a result of their large molecular size and prolonged blood circulation (3, 4). A smaller IgG1-derived Fab’ fragment derived from a murine antibody has been shown to have better tumor penetration, more rapid blood clearance, reduced accumulation in nontarget tissue, and high clinical utility because the Fab’ fragment was reported to have superior imaging properties compared to the conventional diagnostic modalities (5). This indicates that a smaller radiopharmaceutical is a superior diagnostic agent with suitable pharmacodynamic properties. In addition, it has been shown that radiolabeled peptides are extremely useful for the imaging and radiotherapy of neuroendocrine and pulmonary tumors (6, 7). Among the various labeled peptides, the Escherichia coli heat-stable enterotoxin (STh) has been used to image colorectal cancers (8, 9).The STh is known to target guanylate cyclase C (GC-C), a type I transmembrane glycoprotein that is known to be the target that was expressed on intestinal brush border membranes and the human colon cancer T-84 cell line. The glycoprotein is expressed in very low amounts on the extraintestinal tissues and is expressed primarily on the primary and metastatic colon cancer tissues, therefore making it a unique marker for colorectal cancer tumors (10). Peptides such as the STh and uroguanylin have been shown to inhibit the growth of colorectal cancer cells and are efficacious in the treatment of this cancer in animal models (11-13). The enterotoxin has been shown to behave like an agonist for the GC-C receptor, resulting in activation of the guanylyl cyclase that increased the intracellular concentrations of guanosine 3,5-cyclic monophosphate, which directly influenced the fluid and electrolyte balance in the cells (14, 15). Several studies are available in which 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives of STh have been evaluated for in vitro and in vivo activities in mice bearing xenograft tumors (8, 9, 16, 17). These studies are presented in this chapter." @default.
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• W160248964 date "2008-06-10" @default.
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• W160248964 title "[111In]-Labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-heat-stable human Escherichia coli enterotoxin" @default.
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