Abstract: Tumors can be selectively targeted via compounds provided herein according to the formula, or a pharmaceutically acceptable salt thereof, wherein RA and RB are as defined herein. Tumors can be imaged or targeted for therapeutic treatment using compounds described herein where at least one RA or at least one RB group comprises a imaging agent, a therapeutic agent, or a member of a specific binding pair which can be associated with a secondary imaging agent, such as a microbubble for ultrasonic imaging.

Abstract: Highly specific measurements of flow in vessels, such as the coronary artery, can be obtained by processing cubic fundamental information. By showing flow in vessels with a high degree of contrast-to-tissue specificity, ultrasound based 3D contrast agent based coronary artery angiograms may be possible. Measurement and display of the velocity of agent from the cubic fundamental signal is provided simultaneously with display of cubic fundamental energy, such as providing a display map indexed by both energy and velocity. High pulse repetition frequency (PRF) for cubic fundamental detection in conjunction with long velocity measurement intervals may increase low velocity sensitivity and measurement precision. Pulsed wave (PW) Doppler may be improved by using a cubic fundamental sensitive pulse sequence.

Abstract: The present invention includes a construct that comprises at least one microbubble encapsulated within the aqueous core of a microcapsule. The present invention also includes a pharmaceutical composition comprising a construct comprising at least one microbubble encapsulated within the aqueous core of a microcapsule. The present invention further includes a method of imaging a tissue or organ in a subject, a method of delivering a therapeutic cargo to a tissue or organ in a subject, and a method of treating a disease or disorder in a subject.

Abstract: The invention is directed to injectable suspensions of gas-filled microvesicles, as well as methods of preparing and using the same, especially as ultrasound contrast agents.

Abstract: A composition is provided accompanying nanoparticles having diameters in the range of about 100 to 800 nanometers with hollow cores and outer shells with mechanical properties such that they rupture on exposure to predetermined ultrasound energy. The composition is useful for identifying sentinel lymph nodes.

Abstract: The imaging system can comprise a plurality of elongated rails, a scanhead assembly, and a small animal mount assembly. The scanhead assembly is selectively mounted onto a first rail and is constructed and arranged for movement in a linear bi-directional manner along the longitudinal axis of the first rail. The small-animal mount assembly is selectively mounted onto a second rail and is constructed and arranged for movement in a linear bi-directional manner along the longitudinal axis of the second rail. The second rail being mounted relative to the first rail such that the longitudinal axis of the second rail is at an angle to the longitudinal axis of the first rail. The imaging system can also comprise a needle injection assembly that is selectively mounted onto the third rail and is constructed and arranged for movement in a linear bi-directional manner along the longitudinal axis of the third rail.

Abstract: In one aspect of the disclosed subject matter, a method for isolating target microbubbles having a predetermined size range from polydisperse microbubbles is disclosed. The method includes applying a first centrifugal field having a first field strength to a suspension comprising the polydisperse microbubbles for a first duration of time, thereby forming a first infranatant comprising at least a portion of target microbubbles and a first supernatant cake comprising microbubbles having a greater size than the target microbubbles; removing the first supernatant cake; applying a second centrifugal field having a second field strength to the first infranatant for a second duration of time, the second field strength being greater than the first field strength, thereby forming a second supernatant cake comprising at least a portion of the target microbubbles and second infranatant comprising microbubbles having a smaller size than the target microbubbles; and isolating the second supernatant cake.

Abstract: Methods and compositions for using tumor targeting compounds bound to microbubbles to facilitate drug delivery and diagnostic imaging at tumor sites.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-1 receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.

Abstract: Injectable aqueous suspension of microbubbles filled with a biocompatible gas and a method of preparation thereof. At least 10% of the total volume of gas contained in the microbubbles is contained in microbubbles with a diameter of 1.5 ?m or less. The microbubbles can be obtained by preparing an emulsion comprising an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and then reconstituted in an aqueous suspension of gas-filled microbubbles.

Abstract: This invention provides an ultrasonic phantom that can respond to different ultrasonic intensities. Such ultrasonic phantom comprises a gel comprising a low-boiling compound in the form of droplets sealed therein. The invention also provides an assay technique using such phantom. This invention enables regulation of components of droplets, droplet size, and the ultrasonic intensity at which droplets are vaporized upon mixing of droplets with different sizes. This enables visualization of whether or not ultrasound beams that exceed relevant different ultrasonic intensities have been applied.

Abstract: Clinical studies have been conducted and specific dosage formulations developed using polymeric microparticles having incorporated therein perfluorocarbon gases that provide significantly enhanced images of long duration. The dosage formulation includes microparticles formed of a biocompatible polymer, preferably including a lipid incorporated therein, and containing a perfluorocarbon that is a gas at body temperature. The microparticles are provided to a patient in an amount effective to enhance ultrasound imaging in the ventricular chambers for more than 5 minutes or in the mycocardium for more than a minute, in a dose ranging from 0.025 to 8.0 mg microparticles/kg body weight. Preferably the dose ranges from 0.05 to 4.0 mg microparticles/kg body weight. The dosage formulation typically is provided in a vial.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: A composition is provided accompanying nonoparticles having diameters in the range of about 100 to 800 nanometers with hollow cores and outer shells with mechanical properties such that they rupture on exposure to predetermined ultrasound energy. The composition is useful for identifying sentinel lymph nodes.

Abstract: Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component—MAC), thereby modifying the physico-chemical properties thereof. Said MAC comprises a targeting ligand a diagnostic agent or any combination thereof. Optionally a bioactive agent can further be associated to the MAC. The assembly of the invention can be formed from gas-filled microbubbles or microballoons and a MAC having preferably nanometric dimensions, e.g. a micelle, and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.

Abstract: The invention provides compositions and methods for therapeutic and diagnostic applications.

Abstract: Methods for producing echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive compounds as well as targeted imaging and delivery to selected tissues and cells are provided. Compositions containing these echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive agents are also provided.

Abstract: Renal extraction fraction (EF) is determined through use of computed tomography (CT) measurements of arterial blood before and after injection of a radiographic contrast agent into the blood and CT measurements of renal vein blood after injection of the radiographic contrast agent.

Abstract: Ultrasound contrast agents comprising microbubbles of biocompatible gas, e.g. a sulphur halide or a perfluorocarbon, stabilized by opsonisable amphiphilic material, e.g. a membrane-forming lipid such as a phospholipid, especially a negatively charged phospholipid such as a phosphatidylserine, may exhibit prolonged contrast-generating residence time in the liver following intravenous administration.

Abstract: A method for cleaning articles using a surfactant which is effective in the formation of stable microbubbles is provided. The surfactant for microbubble formation contains a (poly)oxyalkylene adduct (A) of an active hydrogen atom-containing compound (a) represented by formula (1) Z-[(AO)n—H]p??(1) wherein Z is the residue of an active hydrogen-containing compound (a) with a valence of P resulting from removal of the active hydrogen atom or atoms; A is an alkylene group containing 1 to 8 carbon atoms; n is an integer of 1 to 400; and p is an integer of 1 to 100. The foaming power of a 0.02% by weight aqueous solution of the (poly)oxyalkylene adduct (A) as measured at 20° C. by the Ross Miles test is not higher than 50 mm.

Abstract: A system and method for determining bubble shell properties using optical scattering. One or more ultrasound contrast agent (UCA) bubbles is placed in an imaging volume and illuminated with a laser. The UCA is exposed to pressure variations (e.g., using pulses of imaging or therapeutic ultrasound), while optical scattering data are collected and processed. The scattering intensity is related to the radius of the UCA. Thus, changes in the radius due to varying pressure conditions results in variations in the scattering intensity. The collected data are processed to provide a radius versus time (RT) relationship. The RT relationship is fit to one or more conventional dynamic models. The fitted empirical data can be used to determine one or more UCA parameters, such as shear modulus and shell viscosity.

Abstract: An apparatus having an echogenic coating of a polymer with hollow spaces present in the polymer. In order to achieve an echogenicity that supplies largely isotropic ultrasonic echo images, the hollow spaces should be microhollow spheres embedded in the polymer.

Abstract: Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

Abstract: The invention relates to a method for the preparation of particles comprising a gas core and shell which particles are suitable for use as contrast agent and as part of a therapeutic composition, especially for drug delivery. These particles show a surprisingly high activation level on provision of ultrasound energy.

Abstract: Compositions and methods for detecting various disorders with targeted microbubbles are disclosed. Specifically, microbubbles comprising glycoprotein Ib (GPIb), ligands for VCAM-1, and ligands for P-selectin such as PSGL-1 are disclosed. Also disclosed are methods for using targeted microbubbles to detect cardiovascular disease comprising administering the disclosed microbubbles to a subject and detecting the microbubbles in the vasculature using ultrasound.

Abstract: An ultrasound imaging system transmits a broad beam of ultrasound into tissues that are perfused with blood containing microbubbles. The ultrasound has an intensity that is sufficient to destroy the microbubbles in the tissues. A plurality of ultrasound imaging beams are then transmitted into the tissues over a sufficient period to allow the tissues to re-perfuse, and reflections from the transmitted imaging beams are processed to provide a perfusion image. The transmitted microbubble-destroying ultrasound may be in the form of a single beam or a plurality of beams that insonify a substantially larger area than the area insonified by the transmitted imaging beams. As a result, the microbubbles are all destroyed at substantially the same time, and the imaging ultrasound is transmitted only into regions of the tissues from which ultrasound reflections will be received.

Abstract: Fibrin-binding peptides having high binding affinity and excellent physical characteristics compared to previously known fibrin-binding peptides are provided. These fibrin-binding peptides may be conjugated to a detectable label or a therapeutic agent and used to detect and facilitate treatment of pathological conditions associated with the presence of fibrin such as thrombic, angiogenic and neoplastic conditions. These peptides may be used in imaging processes such as MRI, ultrasound and nuclear medicine imaging (e.g. PET, scintigraphic imaging., etc.). The peptides may also be used therapeutically. The present invention also provides processes and methods for making and using such peptides and conjugates thereof.

Abstract: A method of making PVA microbubbles including a functionalisation step in which PVA polymeric chains are functionalised at their ends with aldehyde groups, and a subsequent cross-linking step, in which in an air-aqueous solution emulsion with a pH between 4.5 and 5.5 the previously functionalised PVA polymeric chains cross-link by means of an acetalisation reaction, thereby forming the microbubbles. The microbubbles produced are subsequently subjected to a lyophilising step, a filling step in which medicinal gas is introduced and a restoration step of the microbubbles by adding an aqueous solution.

Abstract: This invention addresses the clinical problem of how to optimize biological cell based therapies, such as stem cell therapy. Currently, cell therapies administered by intravenous, intra-arterial, and/or direct tissue injection are limited by the lack of clinically available imaging methods to detect the in vivo fate of the administered cells. There are many efforts underway to develop imaging strategies for stem cells in vivo, including radionuclide and MRI-based approaches. However, these approaches are limited by potential safety issues (e.g. radioactive exposure of stem cells, toxicity of iron particles used for MRI) and difficulty in serial tracking due to complex instrumentation and/or the requirement for repetitive radiation exposure.

Abstract: This invention provides a gas bubble-generating agent that can be used as a contrast medium or a blocking agent in vivo. Such gas bubble-generating agent is produced by a method for producing a gas bubble-generating agent comprising the following steps of: (a) preparing a mixed solution of an amphiphilic substance, an amphiphilic substance comprising a water-soluble polymer chemically bound thereto, a hardly water-soluble substance having a boiling point of lower than 60° C. at atmospheric pressure, and a physiologically acceptable isotonic solution; (b) pressurizing the mixed solution; and (c) centrifuging the mixed solution after the step of pressurization, wherein a molar concentration of the amphiphilic substance in the mixed solution prepared in step (a) is 10 times or more higher than that of the amphiphilic substance comprising a water-soluble polymer chemically bound thereto.

Abstract: Disclosed herein is a method of acoustically delivering a therapeutic composition to a subject pre-diagnosed with a tumor. The method comprises the steps of: parenterally administering the composition from a site remote from a tumor location; and exposing the parenterally administering site to ultrasound waves to target the delivery of the composition. The therapeutic composition comprises an effective amount of a polypeptide or a plasmid nucleic acid encoding the polypeptide, the polypeptide or the nucleic acid is suspended in a dispersed medium; and an effective amount of an microbubble contrast agent; wherein the polypeptide is an angiogenesis inhibitor, and the therapeutic composition is capable of reducing the size of the tumor without the risk of inducing viral vector-induced immunogenicity in the subject.

Abstract: The present invention comprises methods and devices for providing contrast medium for sonography of structures such as ducts and cavities. The invention provides for creation of detectable acoustic variations between two generated phases of a gas and a liquid to make a contrast medium. Sonography is the primary means of imaging but other conventional detection means may also be employed with the present invention.

Abstract: The present invention discloses a method for forming a nano-bubble. The forming method is different from the oil-water emulsion reaction in the prior art. The method comprises: taking an inorganic particle as a nucleus and performing a polymer coating process to coat at least one first polymer on the surface of the nucleus to form an organic/inorganic composite particle; then removing the nucleus of the organic/inorganic composite particle by way of the dissolution of a first solvent to form an impregnated nano-particle; performing a freeze-drying process to remove the first solvent to have the impregnated nano-particle form a hollow nano-particle; and finally dissolving the hollow nano-particle in a second solvent to form the nano-bubble.

Abstract: New targeting or therapeutic compounds which can be incorporated into a composition of gas-filled microvesicles. The invention further relates to gas-filled microvesicles for diagnostic and/or therapeutic use comprising said compounds and to their method of use. The new compounds are compounds of formula M-S-T, wherein: M represents a component capable of associating with an envelope of a gas-filled microvesicle; T represents a component comprising a targeting ligand or a therapeutic agent; and S represents a component comprising at least two bissulfone groups.

Abstract: The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.

Abstract: A method for generating colonography images for colorectal screening of a patient. The patient is administered an amount of radiopaque stool marker which will enable stool present in the patient's colon to be distinguished from soft tissue. The patient's colon is imaged after the stool marker has been administered to generate colonography images. Preparation of the colon is simulated by processing the colonography images to remove marked stool before the images are observed during a diagnosis session.

Abstract: Image enhancing contrast agents for use in diagnostic and/or therapeutic methods, particularly in the form of gas-filled microvesicles, with enhanced stability. The gas-filled microvesicles are stabilized by a layer of amphiphilic material and comprise from 0.15% to 1.0% by moles of a lipid bearing a hydrophilic polymer. The lipid bearing a hydrophilic polymer is preferably a phospholipid linked to polyethyleneglycol.

Abstract: Method and apparatus for continuous infusion to a subject of dispersions in which the dispersed phase is susceptible to flotation or sedimentation. The dispersion is controllably delivered from an upper or lower extremity of an essentially vertically positioned delivery vessel, e.g. syringe 2, and is then admixed with flushing medium, e.g. from infusion minibag 8, prior to administration to the subject. Vertical positioning of the delivery device maximises the distance through which flotation or sedimentation may occur, thereby substantially reducing the effects of separation over a given period of time compared to use of a corresponding horizontal delivery vessel such as a syringe placed in a conventional syringe driver.

Abstract: An apparatus and method for treating subcutaneous tissues using acoustic waves in the range of low acoustic pressure ultrasound waves is disclosed. The method includes injections of enhancing agents, wherein disruption of subcutaneous tissues and subcutaneous cavitational bioeffects are produced by ultrasound waves having a power that will not produce tissue cavitation in the absence of the enhancing agents. The apparatus and method of use is useful for treatment of subcutaneous abnormalities including cellulite, lipomas, and tumors.

Abstract: An ultrasonically active microparticle is taught that includes a porous interior particle having hydrophobic pores, a gas in the hydrophobic pores and a hydrophilic exterior shell surrounding the interior particle forming an ultrasonically active microparticle and allowing the microparticle to be suspended in an aqueous solution.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: In some aspects, there are provided compositions and kits including annexin coupled to ultrasound contrast particles as well as methods utilizing these particles for diagnosis and treatment of pathological conditions characterized by apoptosis.

Abstract: Disclosed is a method of making gas bubbles in a liquid, the bubbles having substantially uniform size suitable for responding to ultrasound or other diagnostic tools. Gas (P2) is forced through one or more pores or nozzles, into the liquid (P1), the nozzles or pores being of substantially uniform diameter, the flow of the gas being controlled to thereby cause the formation of substantially monodisperse gas bubbles in the liquid. Moreover, an apparatus is disclosed for making a suspension of gas bubbles in a liquid of a size suitable for responding to ultrasound or other diagnostic tools. Said apparatus comprises means for forcing a gas through an array of nozzles or pores into the liquid, the nozzles or pores being of substantially uniform diameter, and first means for controlling; a flow parameter of the gas so that gas is suspended as substantially monodisperse gas bubbles in the liquid.

Abstract: A method of making a suspension of particles in a first fluid of a size suitable for responding to ultrasound, by forcing a second fluid (2) through an array of pores (30) into the first fluid (1), the pores being of substantially uniform diameter, and the pressure of the second fluid and a flow rate of the first fluid across the pores being arranged so that shear forces at the pores cause the second fluid to be suspended as substantially monodisperse particles in the first fluid. This can enable a more monodisperse suspension. The array of pores can be an etched silicon array. The suspension can be used as a contrast agent, or can be an emulsion to make droplets of a precursor material, which can be formed into capsules with a core and a shell. A liquid core can be converted to a gas to provide hollow shells.

Abstract: The invention concerns a medicine for treatment of prostate cancer and a corresponding treatment method. The medicine can be supplied to a prostate tumor through the bloodstream, contains an active component and a binding component as well as ultrasound microbubbles. The binding component includes coupling molecules that specifically bind to a determined target molecule formed in the endothelium of tumor-associated blood vessels and that is typical of the tumor or the tumor stage. The active component contains at least one chemotherapeutic substance. The coupling molecules are bound to the outside of the microbubbles and active substance molecules are likewise bound to the outside of the microbubbles or are enclosed by the microbubbles.

Abstract: Microparticles are provided comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microparticles contain a gas, liquid or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The microparticles are capable of passing through the capillary systems of a subject.

Abstract: A contrast agent for ultrasound examination of the prostate has contrast-intensifying particles on an exterior of which at least one binding molecule is present that specifically binds to CEACAM-1. In a method for ultrasound examination of the prostate, such a contrast agent is administered to the patient and a sonography of the prostate is subsequently implemented.

Abstract: Provided are a preparation process of a diagnostic or therapeutic agent having a step of adding, to a first fine emulsion having a particle size of 0.5 ?m or less prepared by applying a predetermined pressure to a first mixture containing a first hydrophobic compound, an emulsifying agent, and an aqueous phase, a second hydrophobic compound compatible with the first hydrophobic compound, thereby preparing a second mixture; and a step of stirring and shaking the second mixture in a hermetically sealed state, thereby embedding the second hydrophobic compound in the first fine emulsion to prepare a second fine emulsion having a particle size of 0.5 ?m or less; a diagnostic or therapeutic agent prepared by the process; and an apparatus for carrying out the process.

Abstract: Apparatus and methods are disclosed for the detection and imaging of ultrasonic harmonic contrast agents. The harmonic echo effect is detected through alternate polarity acquisition of harmonic contrast agent effects, which provides the benefits of suppressing the harmonic components of the transmitted signal while eliminating clutter.