Room: Track 1
Purpose: Majority of tumors have an over-expression of cell surface receptor such as epidermal growth factor receptor (EGFR), which is often correlated to prognosis or how patients respond to targeted therapy. The ability to measure drug-target engagement can facilitate an understanding of drug pharmacokinetics, provide target cancer treatment monitoring, and lead to the development of new therapeutics. Previously, we showed that MRI-coupled paired agent fluorescence molecular tomography (MRI-PAFT) is capable of noninvasively quantifying drug-target engagement in vivo. However, the true potential of a MRI hybrid imaging system exists in simultaneous imaging of both MRI and optical system for functional correlations between the two modalities. Herein, this study aims at comparing MRI contrast agent uptake kinetics with paired agent fluorescence tomography readouts in tumor and normal tissue using dynamic MRI and PAFT.
Methods: The kinetics from the two modalities are extracted to quantify the concentration of epidermal growth factor receptor (EGFR) in orthotopic glioma models noninvasively. Additionally, a novel hyperspectral imaging macrotome system was developed and utilized to image fluorescence agents’ bio-distribution directly after the tomography for validation.
Results: Despite biological variations for drug uptake between samples, strong correlation is observed between Gd uptake kinetic and untargeted optical agent kinetic (R=0.95). Yet, no significant correlation exists between Gd uptake kinetic and receptor targeted optical agent kinetic (R=0.32). Receptor availability (RA) estimated using targeted and untargeted optical agents corresponds with RA calculated using targeted optical agent and Gd (R=0.94).
Conclusion: This result validates that fluorescence tomography measurements of the untargeted imaging agent mimics the behavior of a non-specific contrast agent measured with a clinical imaging modality. This similarity also creates the potential for a fusion imaging system where simultaneous acquisition of targeted imaging probe and MRI contrast agent can be combined to quantify target engagement.
Funding Support, Disclosures, and Conflict of Interest: KT and SCD are inventors on a patent application (#15/402,077) involving cross-modality paired-agent imaging. KSS received financial compensation from LI-COR Biosciences, Inc. for travel and consulting services.