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89Zr-N-Succinyldesferal-anti-CD44v6 chimeric monoclonal antibody U36.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Mar 25 [updated 2010 Apr 22].


Extracellular matrix (ECM) adhesion molecules consist of a complex network of fibronectins, collagens, chondroitins, laminins, glycoproteins, heparin sulfate, tenascins, and proteoglycans that surround connective tissue cells, and they are mainly secreted by fibroblasts, chondroblasts, and osteoblasts (1). Cell substrate adhesion molecules are considered essential regulators of cell migration, differentiation, and tissue integrity and remodeling. These molecules play a role in inflammation, but they also participate in the process of invasion and metastasis of malignant cells in the host tissue (2). Invasive tumor cells adhere to the ECM, which provides a matrix environment for permeation of tumor cells through the basal lamina and underlying interstitial stroma of the connective tissue. Overexpression of matrix metalloproteinases by tumor cells allows intravasation of tumor cells into the circulatory system after degrading the basement membrane and ECM (3). The splice variant v6 of the cell membrane glycoprotein CD44 (CD44v6) is expressed only in a few normal epithelial tissues (e.g., thyroid and prostate gland). CD44 binds to ECM and is associated with cell adhesion, lymphocyte activation, and tumor cell metastases (4, 5). Elevated levels of CD44v6 have been found in epithelial tumors, which are associated with a poor prognosis for cancer patients (5). Anti-CD44v6 chimeric (mouse/human) monoclonal antibody (cMAb) U36 was found not bind to follicles or C cells from normal human thyroid (6). CD44v6 is generally highly expressed in thyroid carcinoma (7). 124I-cMAb U36 was developed for imaging of CD44v6 expression in thyroid carcinoma and other epithelial tumors (8, 9). However, production of 124I is too expensive for routine clinical application. Verel et al. (10) explored the use of 89Zr positron emitter (half-life, 3.27 days) to radiolabel cMAb U36. 89Zr was conjugated to a bifunctional derivative of desferrioxamine B (Df) to cMAB U36 for positron emission tomography (PET) imaging of CD44v6 expression in tumors. 89Zr-N-Succinyldesferal-cMAb U36 (89Zr-N-SucDf-cMAb U36) has been studied in tumor-bearing mice and humans (11, 12).

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