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

Autor: Li C; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., Rounds CC; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., Torres VC; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., He Y; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., Xu X; Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA., Papavasiliou G; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., Samkoe KS; Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA., Brankov JG; Electrical and Computer Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA., Tichauer KM; Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA. ktichaue@iit.edu.
Jazyk: angličtina
Zdroj: Annals of biomedical engineering [Ann Biomed Eng] 2024 Jun; Vol. 52 (6), pp. 1625-1637. Date of Electronic Publication: 2024 Feb 26.
DOI: 10.1007/s10439-024-03476-2
Abstrakt: Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k 3 ) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k 3 (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.
(© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)
Databáze: MEDLINE
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