Radiolabeled Monoclonal Antibodies Specific to the Extracellular Domain of Prostate-Specific Membrane Antigen: Preclinical Studies in Nude Mice Bearing LNCaP Human Prostate Tumor

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate can-cers. PSMA is also expressed on the tumor vascular endothe-lium of virtually all solid carcinomas and sarcomas but not on normal vascular endothelium. PSMA is currently the focus of several diagnostic and therapeutic strategies. We have previ-ously reported on the radiolabeling and in vitro binding proper-ties of monoclonal antibodies (mAbs) (J415, J533, and J591) that recognize and bind with high affinity to the extracellular domain of PSMA (PSMAext). This article reports on the in vivo behavior and tumor uptake of 131I- and 111In-labeled anti-PSMAext mAbs (J415, J533, and J591) and their potential utility for radioimmunotherapy. Methods: In nude mice bearing PSMA-positive human LNCaP tumors, the pharmacokinetics, biodistribution, and tumor uptake of these antibodies was com