Submicron ultrasound contrast agents are gas-filled, double-walled microspheres with a diameter smaller than 1 μm that rupture when exposed to ultrasound energy at megahertz frequencies. These agents differ from traditional ultrasound contrast microbubbles in that the submicron bubbles may serve as extravascular agents. They are small enough to travel through the lymphatic system and to be extravasated from tumor neovasculature. The detection of these agents is limited by their hard shell, which requires high-pressure ultrasound insonation for shell rupture and excitation of the gas bubble. After shell rupture, the gas diffuses rapidly from submicron sized agents. The optimal processing of each echo is important.

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From POINT Biomedical Corp
BiSphere™ is a technology for drug delivery applications by ultrasound. BiSpheres™ consists of microparticles comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microbubbles contains a filling gas, liquid, or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The contrast agent particles are capable of passing through the capillary systems of a subject. The drug-loaded biSpheres™ would be administered intravenously and freely circulate throughout the body, while the drug encapsulated within would remain biologically unavailable. The drug would only be released when the biSpheres become flooded when passing through an externally directed ultrasound field.
The use of biSpheres™ to transport agents to specific sites within the body is expected to substantially increase local efficacy while decreasing systemic side effects or adverse reactions. The biSpheres™ may also serve to protect labile agents from metabolism or degradation. The noninvasive release of a protected, encapsulated agent can be controlled by ultrasound imaging to a depth of 20-30 cm from the skin surface.
The flexibility in size control in the biSphere™ technology has enabled the construction of submicron ultrasound contrast agents suitable for lymphatic imaging, with a diameter in the submicron range. This agent, while much smaller in size than CardioSphere®, is based on the BiSphere configuration: a shell within a shell enclosing a gas. The inner layer, made from a biodegradable polymer, provides the physical structure and controls the acoustic response. The outer layer functions as the biological interface. Each of these layers has been independently tailored to fulfill the specific requirements for lymphatic imaging.

From POINT Biomedical Corp
M1091 is a nitrogen-filled submicron ultrasound contrast agent with a bilayered shell composed of a biodegradable polymer and a human serum albumin outer coating. This agent under development consists of microbubbles that have a peak volumetric diameter of 0.57 μm, and a mean initial diameter of 800 nm, with more than 93% having a diameter smaller than 1 μm. Manipulations in the manufacturing process can generate structures varying in size and wall thickness.
M1091 and M1134 are two agents made of the same polymer with the same relative wall thickness, differing only in the microbubble diameter.

From POINT Biomedical Corp
M1134 is a nitrogen-filled submicron ultrasound contrast agent under development with a bilayered shell composed of a biodegradable polymer and a human serum albumin outer coating. The microbubbles have initial diameters from 500 nm to 1.3 μm, with more than 50% having a diameter smaller than a micron.
M1134 can be used in targeted contrast imaging by entering the lymphatic system after injection into the interstitium and accumulation at lymph nodes.
M1134 and M1091 are two agents made of the same polymer with the same relative wall thickness, differing only in the microbubble diameter.