The choice of A33 antigen as the in vivo target of this initial study was based on the unique features of the antigen-antibody interaction. The expression of the A33 transmembrane glycoprotein is restricted to normal human bowel and colon (95%), gastric (95%), and pancreatic (50%) cancers. Upon binding of anti-A33 mAb, the resulting non-internalized antibody-antigen complex persists on the cell surface for several weeks. Such a lengthy membrane persistence time is rather unique among antibody-antigen complexes, and makes anti-A33 mAb particularly attractive for application to RIT. In contrast, turnover of A33-expressing cells in normal bowel is rapid, occurring every 5-6 days by exfoliation of mucosal cells into the bowel lumen.
Zanzonico P, Carrasquillo JA, Pandit-Taskar N, et al. Positron Emission Tomography (PET)-based Compartmental Modeling of 124I-A33 Antibody: Quantitative Characterization of Patient-specific Tumor Targeting in Colorectal Cancer. European journal of nuclear medicine and molecular imaging. 2015;42(11):1700-1706.