Quantitating antibody uptake in vivo: conditional dependence on antigen expression levels

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Antibodies are crucial cancer therapeutics and imaging agents.
• Discrepancies exist regarding the impact of antigen expression levels on antibody tumor uptake.

Purpose of the Study:

• To investigate the effect of antigen expression level on the tumoral uptake of high-affinity antibodies in vivo.
• To validate a mathematical model predicting antibody uptake.

Main Methods:

• In vivo imaging of fluorescent antibodies in a mouse xenograft model with varying antigen expression.
• Utilized a mathematical model to analyze antibody-tumor interactions.

Main Results:

• Under subsaturating conditions, antibody uptake is limited by vascular delivery, not antigen expression.
• At saturating doses, antibody uptake correlates with the number of available antigen binding sites.
• Smaller micrometastases showed higher antibody targeting than larger tumors.

Conclusions:

• Antibody uptake is dependent on antigen expression for saturating doses and on delivery for subsaturating doses.
• Understanding the balance between biomarker expression and transport is critical for quantitative imaging.
• The predictive model supports the design of more effective antibody-based cancer therapies and imaging probes.