Quantifying receptor occupancy of molecular therapy in vivo (Conference Presentation)

The heterogeneous nature of cancer and universal therapeutic dosing strategies for patients can lead to variation in responders, especially for molecular targeted therapeutics. However, this variation is hard to measure in an individualized, dynamic manner and the relationship between receptor occupancy and patient response is not well developed. We propose the use of fluorescence paired-agent imaging (PAI) to monitor drug-receptor interactions in vivo in individual patients. Paired-agent imaging quantifies in vivo receptor availability by overcoming the confounding factors observed with single agents by isolating the signals of receptor-targeted and perfusion agents co-administered at microdose levels. In non-treated patients, the concentration of receptors available for binding represents the maximum number of therapeutic agent binding sites. We hypothesized that we could calculate the receptor occupancy in real-time by monitoring the dose-dependent decrease in receptor availability using PAI. Results of in vivo animal and kinetic modeling strategies will be presented to demonstrate the ability to calculated receptor occupancy in real-time.