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89Zr-Desferrioxamine B-7E11 anti-prostate-specific membrane antigen monoclonal antibody.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2011 Nov 22 [updated 2012 Feb 23].


Prostate-specific membrane antigen (PSMA) is a cell-surface glycoprotein with a molecular weight of ~100 kDa. It is a unique, type II, transmembrane-bound glycoprotein that is overexpressed on prostate tumor cells and in the neovasculature of most solid prostate tumors, but not in the vasculature of normal tissues (1, 2). PSMA has also been detected in other tissues such as the kidneys, the proximal small intestine, and the salivary glands (2). PSMA has been found to have N-acetyl α-linked acidic dipeptidase (NAALADase) or glutamate carboxypeptidase II activity (3). PSMA may play an important role in the progression of prostate cancer and glutamatergic neurotransmission, as well as in the absorption of folate (4). In the central nervous system, PSMA metabolizes N-acetyl-aspartyl-glutamate, and in the proximal small intestine it removes γ-linked glutamates from poly-γ-glutamate folate and folate hydrolase (2). This unique expression of PSMA makes it an important biomarker as well as a large extracellular target of imaging agents (5, 6). PSMA can be used as a biomarker for the detection of prostate cancer with imaging agents. 7E11, a monoclonal antibody against the cytoplasmic domain of PSMA, has been found to be specific to prostate tumor tissues in humans (7). Tumors often contain dying or necrotic cells with permeable membranes, allowing the binding of antibodies to the intracellular epitope of PSMA. The antibody conjugate (capromab pendetide or CYT-365) was radiolabeled with 111In. 111In-Capromomab pendetide was approved by the United States Food and Drug Administration in 1996 for the detection of prostate carcinoma and soft tissue metastases in prostate cancer patients (8). However, the results obtained with this antibody are not entirely reliable (9). In addition, this antibody has limited access to tumors and may produce low signal/noise ratios because the target is the intracellular domain of PSMA (10). Newer monoclonal antibodies (e.g., J591) against the extracellular domain of PSMA are being developed for imaging and immunotherapy of prostate cancer (11, 12). Ruggiero et al. (13) conjugated 7E11 with desferrioxamine B (DFO) and radiolabeled the product with 89Zr to form 89Zr-DFO-7E11 for positron emission tomography (PET) imaging of PSMA expression as a marker for dead or dying prostate tumor cells.

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