A newly emerging technique of assessing receptor occupancy (RO)^1,2 via dynamic monitoring through paired agent imaging (PAI)^3,4 could be a valuable tool for individual drug dosing strategies. In previous work (submitted for publication), there was an unexpected increase of signal in the targeted fluorophore channel upon introduction of a blocking agent, of which was likely accounted for through binding potential calculations using an untargeted probe and a reference tissue.^5,6 We explore this phenomenon using a compartmental model and system of ODEs, as well as verify PAI’s ability to approximate RO dynamically. A 12-compartment model was designed that contained 6 compartments describing the kinetics of a targeted and untargeted fluorescent probe, alongside 6 compartments to allow for the introduction of a blocking agent at 300 minutes. Simulation parameters were informed via fluorescence studies of homogenized tissues before and after administration of a blocking agent, and results were compared with in vivo animal blocking studies. The peak in targeted fluorophore fluorescence post-blocking could be described by incorporating a “peripheral” tissues compartment, separate from that of the tumor and reference tissue compartments. This compartment was designed to mimic the blood flow, size, tissue extravasation, as well as EGFR concentration seen in the liver, yielding similar curves to those seen in vivo. Further, a deconvolution approach to binding potential calculations⁷ was found to approximate true RO +/- 10% error within 30 min of administering the blocking agent using varying values of extravasation rate, K₁, in the “other” compartment as well as differing concentrations of available receptors in both the “other” and “tumor” compartments.

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