Dynamic Tracking of In Vivo Receptor Availability in Tumor Using Paired-Agent Imaging

Area of Science:

• Biomedical imaging
• Molecular imaging
• Cancer research

Background:

• Quantitative assessment of receptor availability (RA) is crucial for drug development and clinical practice.
• Head and neck cancer (HNC) models require dynamic tracking of receptor availability for therapeutic assessment.

Purpose of the Study:

• To evaluate paired-agent imaging (PAI) for dynamic quantification of epidermal growth factor receptor (EGFR) availability in HNC models.
• To assess the impact of imaging agent dose and EGFR blocking on RA estimation.

Main Methods:

• Xenograft HNC tumor-bearing mice were coadministered varying doses of ABY-029 and IRDye 700DX.
• Fluorescence imaging was performed, followed by administration of Z03115 (test), human EGF (positive control), or PBS (vehicle).
• Kinetic fluorescence and PAI curves were analyzed to determine RA changes.

Main Results:

• PAI demonstrated a decrease in RA upon EGFR blocking, consistent with expectations.
• Direct fluorescence measurements of the imaging agent alone showed non-quantifiable increases and could not reliably assess RA.
• No significant difference in preblocking RA was observed across different ABY-029 doses.

Conclusions:

• PAI enables dynamic and accurate monitoring of receptor availability in individual animals, irrespective of imaging agent dose.
• PAI is a robust imaging strategy for optimizing drug dosing in pharmaceutical development and enabling patient-specific molecular therapeutics.