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Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

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Quantifying Imaging Agent Binding and Dissociation in 3-D Cancer Spheroid Tissue Culture Using Paired-Agent

Chengyue Li¹, Cody C Rounds¹, Veronica C Torres¹

¹Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA.

Annals of Biomedical Engineering

|February 27, 2024

Summary

This summary is machine-generated.

A new method quantifies drug and imaging agent binding kinetics in 3D cancer models. This approach accurately predicts agent behavior based on receptor concentration, aiding cancer diagnosis and drug development.

Keywords:

Drug affinity Epidermal growth factor receptor Fluorescence Tracer kinetic modeling

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Area of Science:

Biomedical imaging
Cancer research
Pharmacokinetics

Background:

Binding kinetics are crucial for cancer diagnosis and therapeutics.
Existing methods lack consideration for the 3D biological tissue environment.
A novel methodology is needed to accurately quantify binding in complex biological systems.

Purpose of the Study:

To develop and validate a new methodology for assaying agent binding and dissociation in 3D tissue culture.
To quantify the binding kinetics of an epidermal growth factor receptor (EGFR)-targeted agent (ABY-029) in various cancer cell lines.
To establish a correlation between binding kinetics and receptor concentration.

Main Methods:

Utilized paired-agent molecular imaging principles in 3D tissue culture.
Measured the uptake of ABY-029 and a control agent in 3D cancer spheroids.
Applied a compartment model to kinetic data to estimate binding and dissociation rate constants.

Main Results:

A significant correlation was found between the apparent association rate constant (k3) and receptor concentration (r=0.99, p<0.05).
Effective k3 values differed significantly between cell lines with varying EGFR expression levels (p<0.05).
The model demonstrated a binding affinity profile comparable to gold-standard methods.

Conclusions:

The developed low-cost methodology accurately quantifies imaging agent and drug binding affinity in 3D tumor spheroid models.
This method can guide the timing of molecular imaging in surgery and inform drug development strategies.
The findings highlight the importance of 3D environments in assessing binding kinetics for clinical applications.