I-Anti-PSCA 2B3 minibody

Prostate stem-cell antigen (PSCA) is a cell-surface protein (123 amino acids) that is expressed in normal prostate tissue and overexpressed in prostate cancer tissues (1). PSCA expression is detected in >80% of patients with local disease including high expression in bone metastases (2). Elevated levels of PSCA are correlated with increased tumor stage, grade, and androgen independence (3). PSCA overexpression is also observed in bladder and pancreatic cancers (4). The anti-PSCA murine monoclonal antibody (mAb) 1G8 has been shown to have anti-tumor activity (5). A humanized version of the 1G8 mAb (hu1G8) has been radiolabeled as I-hu1G8 for tumor imaging in mice (6). However, it took 1 week to observe an enhanced target/background ratio with positron emission tomography because of the slow kinetics of the mAb. A hu1G8 minibody fragment (2B3) (a dimer of scFvs-C3 with a linker composed of 18 amino acids; molecular weight,80 kDa) has been developed and labeled as I-2B3 minibody for tumor targeting studies (7).