Development of near-infrared paired-agent imaging for in vivo quantification of drug receptor occupancy in tumor

Yichen Feng; Kenneth M. Tichauer; Kimberley S. Samkoe

doi:10.1117/12.2650968

14 March 2023 Development of near-infrared paired-agent imaging for in vivo quantification of drug receptor occupancy in tumor

Yichen Feng, Kenneth M. Tichauer, Kimberley S. Samkoe

Author Affiliations +

Proceedings Volume 12357, Visualizing and Quantifying Drug Distribution in Tissue VII; 1235709 (2023) https://doi.org/10.1117/12.2650968
Event: SPIE BiOS, 2023, San Francisco, California, United States

Abstract

Receptor occupancy (RO) correlates the dose of drug administered to the percentage of receptors occupied by the drug compound, which helps decide dosing of drug candidates entering clinical trials, and tailor drug dosage for individualized therapies. However, in vivo measurement of RO in solid tumor is hindered by both tissue properties and technical limitations. Here we present the progress of developing a near-infrared, paired-agent imaging (PAI) approach for real-time measurement of anti-tumor drug RO in vivo. In this study, xenograft murine model with orthotopic tumor implant was imaged using a pair of imaging agent: ABY-029, an affibody-dye conjugate, targeting epidermal growth factor receptor (EGFR), together with IRDye 680LT, a pharmacokinetically similar probe devoid of EGFR specificity. Concentration of tumor EGFR free of drug binding was quantified by binding potential (BP), a parameter calculated from fluorescence signals of the agent pair. We demonstrated that BP was decreased by subsequent administration of drug homolog, indicating drug-EGFR engagement in the tumor. The results demonstrated the ability of PAI to reflect displacement of EGFR-bound ABY-029 by anti-EGFR drug molecules, and the potential to be applied for in vivo RO measurement.

Conference Presentation

Citation Download Citation

Yichen Feng, Kenneth M. Tichauer, and Kimberley S. Samkoe "Development of near-infrared paired-agent imaging for in vivo quantification of drug receptor occupancy in tumor", Proc. SPIE 12357, Visualizing and Quantifying Drug Distribution in Tissue VII, 1235709 (14 March 2023); https://doi.org/10.1117/12.2650968

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