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111In-CHX-A''-DTPA-anti-mindin/RG-1 monoclonal antibody 19G9.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2009 Nov 16 [updated 2009 Dec 03].


Extracellular matrix (ECM) adhesion proteins 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 and atherogenesis, 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 and other proteases by tumor cells allows intravasation of tumor cells into the circulatory system after degrading the basement membrane and ECM (3). Mindins are members of the mindin/F-spondin family of secreted ECM proteins (4). A human mindin homolog, mindin/RG-1, is expressed selectively in prostate tissues, and its expression level is elevated in some prostate tumors (5). Mindin/RG-1 protein expression is maintained in >80% of prostate cancers metastatic to bone or lymph nodes as well as in locally recurrent tumors in androgen-unresponsive patients. Furthermore, mindin/RG-1 expression in other normal tissues is lower than that expressed in the prostate. The fully humanized monoclonal antibody (mAb) 19G9 was generated against the mindin/RG-1 protein. Conjugation of mAb 19G9 with the bifunctional chelator [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans(S,S)-cyclohexane-1,2-diethylene triamine-pentaacetic acid (CHX-A''-DTPA) produced CHX-A''-DTPA-19G9, which was used for 111In labeling (5). 111In-CHX-A''-DTPA-19G9 has been evaluated in nude mice bearing human LNCaP tumor xenografts (5, 6).

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