124I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET

Abstract

The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients. Methods: Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide 124I ( 124IhuA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination. Results: PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of 124I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ∼0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ∼0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%. Conclusion: The in vivo biodistribution of 124I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions. Copyright © 2011 by the Society of Nuclear Medicine, Inc.