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

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

Authors:	O'Donoghue, J. A.; Smith-Jones, P. M.; Humm, J. L.; Ruan, S.; Pryma, D. A.; Jungbluth, A. A.; Divgi, C. R.; Carrasquillo, J. A.; Pandit-Taskar, N.; Fong, Y.; Strong, V. E.; Kemeny, N. E.; Old, L. J.; Larson, S. M.
Article Title:	(124)I-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.
Keywords:	colorectal cancer; radioimmunotherapy; 124i; immuno-pet; hua33
Journal Title:	Journal of Nuclear Medicine
Volume:	52
Issue:	12
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2011-12-01
Start Page:	1878
End Page:	1885
Language:	English
DOI:	10.2967/jnumed.111.095596
PROVIDER:	scopus
PUBMED:	22068895
PMCID:	PMC3394180
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-83755168354&partnerID=40&md5=612db6cca1bbc759ca391c7c5cf365da
Notes:	--- - "Export Date: 1 February 2012" - "CODEN: JNMEA" - "Source: Scopus"