RT Journal Article SR Electronic T1 124I-huA33 Antibody Uptake Is Driven by A33 Antigen Concentration in Tissues from Colorectal Cancer Patients Imaged by Immuno-PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1878 OP 1885 DO 10.2967/jnumed.111.095596 VO 52 IS 12 A1 Joseph A. O'Donoghue A1 Peter M. Smith-Jones A1 John L. Humm A1 Shutian Ruan A1 Daniel A. Pryma A1 Achim A. Jungbluth A1 Chaitanya R. Divgi A1 Jorge A. Carrasquillo A1 Neeta Pandit-Taskar A1 Yuman Fong A1 Vivian E. Strong A1 Nancy E. Kemeny A1 Lloyd J. Old A1 Steven M. Larson YR 2011 UL http://jnm.snmjournals.org/content/52/12/1878.abstract AB 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 (124I-huA33) 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.