Tumor targeting with radiolabeled antibodies in a human carcinoembryonic antigen transgenic mouse model

Area of Science:

• Immunology
• Oncology
• Biomedical Engineering

Background:

• Carcinoembryonic antigen (CEA) is a tumor marker relevant for cancer detection and therapy.
• Developing targeted radioimmunodetection and radioimmunotherapy requires effective delivery agents.
• Mouse models are crucial for evaluating the efficacy and specificity of such agents.

Purpose of the Study:

• To evaluate the biodistribution and tumor targeting of a radioiodinated monoclonal antibody (MAb), T84.66, in mice transgenic for the CEA gene.
• To assess the specificity of antibody uptake in both antigen-positive and antigen-negative tumors.
• To validate the utility of the CEA transgenic mouse model for preclinical studies.

Main Methods:

• Utilized mice genetically engineered to express the carcinoembryonic antigen (CEA).
• Administered a radioiodinated monoclonal antibody (MAb), T84.66, and tracked its biodistribution and tumor uptake.
• Assessed antibody specificity by comparing uptake in CEA-transfected tumors versus antigen-negative parental tumors and human tumor xenografts.
• Evaluated antibody localization in normal tissues of both transgenic and non-transgenic mice.

Main Results:

• High CEA-expressing tumors showed significant uptake (%ID/g approaching 30% at 48 hr).
• Tumor uptake was 5-8-fold higher in antigen-positive tumors compared to antigen-negative ones.
• Immunoscintigraphy successfully visualized only antigen-positive tumors.
• Specific localization was observed in the large bowel of transgenic mice, indicating targeting of antigen-positive normal tissues.
• No circulating antigen-radio-antibody complexes were detected, and blood clearance was similar between groups.

Conclusions:

• The CEA transgenic mouse model accurately reflects tumor targeting and biodistribution of radioiodinated MAbs.
• This model demonstrates specific tumor localization related to the level of CEA expression.
• The findings support the use of this transgenic model for developing novel radio-immunodetection and treatment strategies for CEA-expressing carcinomas.