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Ultrasound Activatable Nanodroplets Targeted to EGFR for Molecular Imaging with High-Frequency Ultrasound

T Mitcham1,2*, D Nevozhay1 , S Lai1 , K Sokolov1,2,3 , R Bouchard1,2 , (1) University of Texas MD Anderson Cancer Center, Houston, TX, (2) MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, (3) University of Texas, Austin, TX


(Tuesday, 7/31/2018) 4:30 PM - 6:00 PM

Room: Room 207

Purpose: To assess feasibility of using high-frequency ultrasound (US) to activate and visualize EGFR-targeted perfluorocarbon (PFC)-based targeted activatable nanodroplets (TANs), demonstrating the potential of PFC-based TANs as a non-radioactive, molecular contrast agent that can be noninvasively visualized with high contrast and resolution using clinical high-frequency US.

Methods: PFC-based TANs are able to transition from a sub-US-resolution nanodroplet to a microbubble visible under high-frequency US upon activation by exposure to an US pulse of sufficient mechanical index (MI). To activate the TANs, Transmit Power, Gate, and Beamwidth settings were modulated in the VisualSonics Vevo 2100 system’s Nonlinear Contrast Mode at a 12.5-MHz transmit frequency. Once a TAN-activation protocol was optimized, enhancement of nonlinear contrast from regions of interest (ROIs) containing TANs were assessed in an in vitro environment. A phantom was designed with wells cast in gelatin to allow for gelatin-bound inclusions of bare PFC-based TANs, untagged EGFR(+) FaDu cancer cells, and FaDu cells incubated with either non-targeted or EGFR-targeted PFC-based TANs. 3D B-mode and nonlinear US scans were acquired with a 12.5-MHz transmit frequency for all target types before and after activation pulses. Contrast enhancement was assessed via a comparison of matched ROIs from pre-and post-activation imaging data.

Results: US-transmit parameter settings were optimized to consistently activate PFC-based TANs on the Vevo system. Using these parameters, EGFR-targeted TANs experienced a 23±3 dB contrast enhancement from its pre-activation baseline compared to just a 9±3 dB enhancement for the non-targeted sample, while untagged cells remained anechoic.

Conclusion: In addition to improved spatial resolution, which could be critical for superficial clinical targets, high-frequency ultrasound affords nonlinear imaging with a transmit frequency closer to resonance for 1-micrometer bubbles (i.e., the nominal post-activation diameter). This work demonstrates the potential for the use of PFC-based TANs as a molecular imaging contrast agents for high-frequency US.


Ultrasonics, Contrast Agent


IM- Ultrasound : Contrast imaging

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