Preclinical animal ultrasound microbubble contrast agent

1、 Product Introduction
1.1 Physical Structure
USphereTM bubble contrast agent 系Preclinical animal ultrasound microbubble contrast agent(For scientific research purposes only), after intravenous injection, it can enhance the ultrasound signal in the blood, achieving the purpose of enhancing cardiovascular disease diagnosis or tumor detection. This ultrasound contrast agent uses Octafluoropropane (Perflutren, C3F8) gas as the core gas and a single-layer membrane microbubble with phospholipids material as the shell layer. As shown in Figure 1, through the self-assembly ability of phospholipids, the phospholipid layer can form an effective protective film to slow down gas diffusion, prevent microbubbles from melting into larger bubbles, and maintain stable circulation in the body, enhancing contrast time. The phospholipid shell is usually composed of 2-3 types of phospholipids; The surface is modified with polyethylene glycol (PET) to avoid aggregation between phospholipid shells, and its biocompatibility is also improved.

1.2 Shell Composition
At present, the mainstream shell materials for ultrasound contrast agents are mainly phospholipids, which have the advantage of forming a good elastic single-layer membrane to protect microbubbles and generate stable vibrations during ultrasound emission, thereby exhibiting excellent acoustic properties and enhancing ultrasound imaging effects.
1.3 Gas composition analysis
Currently, most commercially available ultrasound contrast agents use perfluorocarbons. Compared to air, perfluorocarbons have a larger molecular weight, extremely low water solubility, and slow diffusion rate; Therefore, the theoretical energy barrier for perfluorocarbon compounds to penetrate phospholipid membranes is relatively high. Perfluorocarbons can effectively slow down the deflation rate of microbubbles, thereby enhancing the contrast time of microbubbles. The gas composition used by USphereTM is also perfluorocarbon.

2、 Comparison and Advantage Analysis of Competitive Products
Common commercial ultrasound contrast agents include OptisonTM (GE Healthcare) from the US and Definity ® （Lantheus Medical Imaging）、 European SonoVue TM (Braco) and Japanese Sonazoid TM (GE Healthcare). The comparison table of common commercial contrast agents is shown in Table 1.
Advantage 1: UsphereTM has a very excellent particle size distribution compared to other products (as shown in Figure 2), and its microbubble resonance frequency is more suitable for the current range of medical instruments, greatly improving the intensity of ultrasound signals. Secondly, a good particle size distribution can control the biological effects caused by stable cavitation and inertial cavitation, thereby reducing their potential risk in detecting cardiovascular diseases and enhancing their safety in drug delivery.
Advantage 2: The UspherTM series products have smaller particle sizes, providing more detailed imaging quality while still maintaining backscatter intensity in deep tissues.
Advantage 3: The concentration of microbubbles per unit volume of UspherTM can reach 2.5x1010Bubbles/mL, which is the highest concentration among similar products. Due to its small particle size and high concentration, angiography of the tumor site is more pronounced.
Advantage 4: UsphereTM has good stability and suspension characteristics (as shown in Figure 3), and can be used for certain acoustic studies (such as ultrasonic field scanning and fluid state analysis).
Advantage 5: The circulation time of UspherTM in vivo can reach 6-15 minutes (as shown in Figure 4), which is beneficial for in vivo experiments. After opening and activating, it can maintain high quality for three days, making it convenient for in vivo experiments. However, SonoVue TM, which currently has a high sales volume, only has a 6-hour usage time after opening.

Other extended applications include:
(1) Cardiovascular diagnosis
Assist in observing ventricular wall motion, diagnosing atrial or ventricular diaphragmatic defects, determining the degree and location of myocardial ischemia, assisting in the diagnosis of coronary heart disease, evaluating balloon dilation surgery, and tracking postoperative vascular reocclusion.
(2) Tumor diagnosis
Tumor blood perfusion (Figure 6) and tumor metastasis diagnosis, breast cancer detection.

Figure 7 Inject Tracer into Window Chamber Model and observe pharmacokinetics
Figure 7 Pharmacokinetic Analysis of Tracer in Mice Window Chamber Model

Figure 8: IVIS tracking of ultrasound driven drug release
Figure 8 Ultrasound driven drug (tracer) delivery and release in vivo

Figure 9: Tracer releases fluorescent substances driven by ultrasound in cells
Figure 9 Ultrasound driven drug (tracer) delivery and release in vitro