TY - JOUR T1 - <sup>124</sup>I-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 SP - 1878 LP - 1885 DO - 10.2967/jnumed.111.095596 VL - 52 IS - 12 AU - Joseph A. O'Donoghue AU - Peter M. Smith-Jones AU - John L. Humm AU - Shutian Ruan AU - Daniel A. Pryma AU - Achim A. Jungbluth AU - Chaitanya R. Divgi AU - Jorge A. Carrasquillo AU - Neeta Pandit-Taskar AU - Yuman Fong AU - Vivian E. Strong AU - Nancy E. Kemeny AU - Lloyd J. Old AU - Steven M. Larson Y1 - 2011/12/01 UR - http://jnm.snmjournals.org/content/52/12/1878.abstract N2 - 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. ER -