SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

Abstract

The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations—SonoVue®, Sonazoid™, and Optison™—were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh–Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.

Delivery of Anticancer Drugs Using Microbubble-Assisted Ultrasound in a 3D Spheroid Model

“…Surprisingly, the increase in MB concentration did not affect the permeabilization efficiency of spheroids (Figure A,B). The data available in the literature showed that the permeabilization of cells and tissues is dependent on the MB concentration. − In the near future, the influence of a wider range of MB concentrations as well as the type of MBs ( i.e. , soft- vs hard-shelled MBs, bare vs targeted MBs, poly- vs monodisperse MBs, etc. )…”

Differentiation Between Granulomatous Lobular Mastitis and Breast Cancer Using Quantitative Parameters on Contrast-Enhanced Ultrasound

“…Sonovue was the most widely used UCA in previous studies, but its mechanical properties limit its use with high-frequency linear array probes for breast scanning and its capacity for long-term imaging. In our study, Sonovue imaging could only last 4 minutes, limiting access to high-quality imaging parameters compared to the more stable Optison or Sonazoid (28). External perfusion software, such as VueBox (Bracco, Italy), with integrated motion correction, allows for a more detailed evaluation of micro vascularization in terms of wash-in and wash-out kinetics because cine loops for up to 2min can be evaluated and more parameters are determined (29).…”

Diagnostic performance of contrast‐enhanced ultrasound in diagnosing hepatic artery occlusion after liver transplantation: A systematic review and meta‐analysis

“…Study population characteristics included number of patients, age, gender, number of liver transplantation, type of transplant, and follow up duration. Abstracted data included contrast agents (SonoVue‐sulfur hexafluoride lipid shells, Levovist‐lipid/galactose shell, and Optison‐octafluoropropane protein shells), 17, 18 indication for CEUS, diagnostic criteria for CEUS, reference standard, prevalence of HAO, prevalence of HAS, prevalence of HAT, sensitivity, specificity, true positive, false positive, false negative, and true negative. This information was either obtained directly from the study or calculated using other information.…”