Zr-Desferrioxamine B-J591 anti-prostate-specific membrane antigen monoclonal antibody

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 was found to have -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 -acetyl-aspartyl-glutamate, and in the proximal small intestine it removes γ-linked glutamates from poly-γ-glutamate folate and folate hydrolase (2). PSMA can be used as a marker for the detection of metastatic cancers with imaging agents. Although a commercially available monoclonal antibody (In-labeled Capromomab pendetide (In-CYT-356)) is in clinical use for the detection of prostate cancer, the results obtained with this antibody are not entirely reliable (5). 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 (6, 7). J591, a monoclonal antibody against the extracellular domain of PSMA, has been humanized, and the humanized J591 was conjugated with desferrioxamine B (DFO) and radiolabeled with Zr to form Zr-DFO-J591 for imaging PSMA expression in prostate tumors (8). Zr-DFO-J591 exhibited high specific binding and tumor/muscle contrast in positron emission tomography (PET) imaging in PSMA-positive prostate tumors in nude mice.