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Preclinical assessment and pilot study using anti-CEA monoclonal antibody 1B2 for colorectal carcinoma imaging
Akihiko Takeda1, Hideaki Shimada, Shin-ichi Okazumi
1Department of Academic Surgery Graduate School of Medicine, Chiba University, Chiba, Japan. aktake@saitama-med.ac.jp
Background/Aims:
Preclinical assessment of radio-labeled monoclonal antibodies is essential to the understanding of target-specific tumor localization. The purpose of this study is to prepare for fundamental evaluation of antibodies and to validate the clinical usefulness of the candidate considered useful for practice through preclinical assessment.
Methodology:
The immunoreactivity and affinity constant of three kinds of monoclonal antibody (1A4, 1B2, 4H11: CEA-specific) were evaluated with the method of cell binding assay. Tumor localization and biodisrtibution were performed in tumor-bearing athymic mice. Five patients of colorectal cancer underwent radioimmunodetection with 99mTc. Histological analysis was performed to evaluate the tumor localization of injected antibody.
Results:
The immunoreactive fraction value of 1B2 is the highest than the other antibodies. The difference between the antibody affinities among three antibodies although were rather small. In an animal model, 1B2 obtained more highly tumor targeting and cleared more rapidly from the blood than the other two antibodies did. Pilot study using 1B2 was successful in all cases without background imaging. Visualization of tumor sites surgically removed revealed positive CEA and IgG immunostaining.
Conclusion:
The preparation for preclinical assessment of the characteristic parameters is practically valuable for clinical application of radiolabeled antibodies.
