124I-huA33 Antibody Uptake Is Driven by A33 Antigen Concentration in Tissues from Colorectal Cancer Patients Imaged by Immuno-PET
- 8 November 2011
- journal article
- clinical trial
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 52 (12), 1878-1885
- https://doi.org/10.2967/jnumed.111.095596
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 (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.This publication has 34 references indexed in Scilit:
- 124I-huA33 Antibody PET of Colorectal CancerJournal of Nuclear Medicine, 2011
- A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic CarcinomaCancer Research, 2008
- A33 antigen displays persistent surface expressionCancer Immunology, Immunotherapy, 2008
- In vitro and in vivo characterization of 177Lu-huA33: A radioimmunoconjugate against colorectal cancerNuclear Medicine and Biology, 2006
- In Vitro Characterization of 211At-Labeled Antibody A33—a Potential Therapeutic Agent Against Metastatic Colorectal CarcinomaCancer Biotherapy & Radiopharmaceuticals, 2005
- Phase I Trial of 131I-huA33 in Patients with Advanced Colorectal CarcinomaClinical Cancer Research, 2005
- Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphomaBlood, 2004
- Relevance of External Beam Dose–Response Relationships to Kidney Toxicity Associated with Radionuclide TherapyCancer Biotherapy & Radiopharmaceuticals, 2004
- Analysis of the Regulation of the A33 Antigen Gene Reveals Intestine-specific Mechanisms of Gene ExpressionPublished by Elsevier BV ,2002
- Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphenylglycolurilBiochemical and Biophysical Research Communications, 1978