PT  - JOURNAL ARTICLE
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
TI  - <sup>124</sup>I-huA33 Antibody Uptake Is Driven by A33 Antigen Concentration in Tissues from Colorectal Cancer Patients Imaged by Immuno-PET
AID  - 10.2967/jnumed.111.095596
DP  - 2011 Dec 01
TA  - Journal of Nuclear Medicine
PG  - 1878--1885
VI  - 52
IP  - 12
4099  - http://jnm.snmjournals.org/content/52/12/1878.short
4100  - http://jnm.snmjournals.org/content/52/12/1878.full
SO  - J Nucl Med2011 Dec 01; 52
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.