Ultrasound Contrast Agents for Tumor Perfusion Imaging and as Drug Carriers Boriphat Methachan, Drexel University
Dynamic data on tumor vasculature are important for efficiency of diagnosis and cancer therapy. In this study, gas bubbles stabilized by surfactants were used as contrast agents in ultrasound imaging. Two agents were developed in our laboratory: 1) a perfluorocarbon gas bubble contrast agent, ST68, stabilized with Span60 and Tween 80 with a bubble population ranging from 1-4 micrometer diameter, and 2) SE61, with a Span60, d-α tocopheryl polyethylene glycol 1000 succinate, or TPGS shell and comprised of population of gas bubbles with a substantial number of nano-sized bubbles, has bubble sizes ranging from 100 nanometers to 3 micrometers. SE61 was developed to see if the smaller sized bubbles would yield better ultrasound imaging for tumor perfusion deeper into the tumor bed. In-vitro study showed both agents provide good echogenicity (return of ultrasound back to the collector). Power-Doppler ultrasound imaging was used in vivo to analyze the tumor perfusion for both agents in an animal (rat) study. Tumor coverage and time were plotted and analyzed by comparing parameters in wash-in and wash-out phases. The results showed that both agents gave good tumor coverage. However, SE61 provided better perfusion imaging than ST68. Subsequent experiments showed that Paclitaxel, a promising anti-tumor agent with poor water solubility, could intercalate into the bubble shell, resulting in the change in echogenicity and stability of the agents in the ultrasound beam. This study portends the better perfusion of the nanobubbles when used for tumor vasculature imaging and can be useful in our long-term goal as drug carriers for cancer therapy.