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: A method for identifying a molecule that binds an irradiated tumor in a subject and molecules identified thereby. In some embodiments, the method includes the steps of (a) exposing a tumor to ionizing radiation; (b) administering to a subject a library of diverse molecules; and (c) isolating from the tumor one or more molecules of the library of diverse molecules, whereby a molecule that binds an irradiated tumor is identified. Also provided are targeting ligands that bind an irradiated tumor and therapeutic and diagnostic methods that employ the disclosed targeting ligands.

Abstract: Use of pregnancy-associated plasma protein-A as a marker for inflammatory conditions, and in particular, for acute coronary syndromes is described.

Abstract: The presently disclosed subject matter provides ligands for detecting and imaging cancer cells and tumors, and for guided delivery of an active agent to cancer cells and tumors. In some embodiments the ligands comprise an antibody fragment, wherein the antibody fragment comprises a VHH domain. In some embodiments a composition is provided for targeting of cancer cells or tumors. Also provided are methods for delivery of a composition to a target tissue or tumor in a subject. Also provided are methods for imaging a target tissue or tumor in a subject. In some embodiments methods for treating a tumor in a subject are provided. Also provided are methods for diagnosing a tumor in a subject.

Abstract: The present invention relates to a CD9-specific human antibody, more precisely a CD9-specific human antibody composed of human derived CD9-specific complementarity determining region (CDR) and framework region (FR). The human antibody of the present invention recognizes CD9 extracellular loop 2 domain (CD9-ECL2) as an epitope and thereby strongly binding thereto. The human antibody of the present invention also has CD9 antigen neutralizing effect and at the same time inhibiting effect on tumor cell lines. Therefore, it can be effectively used for the prevention and treatment of cancer overexpressing CD9.

Abstract: Nano-particles are molded in nano-scale molds fabricated from non-wetting, low surface energy polymeric materials. The nano-particles can include pharmaceutical compositions, taggants, contrast agents, biologic drugs, drug compositions, organic materials, and the like. The molds can be virtually any shape and less than 10 micron in cross-sectional diameter.

Abstract: Dye conjugates of template-fixed ?-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 14 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, or Pro or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties, and are useful for cancer therapy; diagnostic imaging; for detection of tumors and other abnormalities; for photoacoustic tumor imaging, detection and therapy; and for sonofluorescence tumor imaging, detection and therapy. The various dyes forming part of these conjugates are useful over the range of 300-1200 nm, the exact range being dependent upon the particular dye. These dye conjugates of ?-hairpin peptidomimetic can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

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: The present invention provides a substantially non-lytic, non-cytotoxic anchor peptide that is capable of stably inserting into lipid membranes. In particular, the invention provides nanoparticles comprising stably inserted anchor peptides, which may be conjugated to a variety of different cargo complexes.

Abstract: Methods and compositions are described for targeting therapeutic and diagnostic molecules to particular types of cells using targeting antibodies or other targeting moeities.

Abstract: Ghrelin analogues having high affinity for a target receptor in diseased cells are provided, as well as methods of diagnosis and treatment utilizing such analogues.

Abstract: The present teachings relate to echogenic coatings and medical devices coated with an echogenic coating. The echogenic coating can be prepared from a composition comprising a polymer and an effervescent agent in one or more anhydrous solvents.

Abstract: The present invention provides polypeptides, peptide dimers, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD<1 ?M), and dimer and multimeric constructs comprising these polypeptides, particularly contrast agents. Also provided are methods for monitoring and evaluating the therapeutic effectiveness of treatment protocols for diseases associated with angiogenesis or endothelial cell hyperproliferation, such as cancer, using contrast agents of the invention.

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

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

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

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: The invention relates to a method for targeting an imaging agent to cells of an animal to detect localized infections. More particularly, localized infections are detected by targeting imaging agents to inflammatory cells having receptors for a vitamin by using vitamin-imaging agent conjugates.

Abstract: Methods and compositions are described for targeting therapeutic and diagnostic molecules to particular types of cells using targeting antibodies or other targeting moeities.

Abstract: The present invention relates to a method of synthesizing acoustically active biodegradable hollow spheres with a size below 1 micron. By using water soluble organic solvents and pegylated polymers, direct precipitation of these spheres is facilitated leading to a fast and convenient preparation route.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different.

Abstract: A drug delivery balloon (10) has a drug thereon in the form of crystalline particles (12), the drug having a predetermined size distribution. Optionally marker particles (14, 16) are also provided. A texturized coating (18), a cap layer (20) and/or other methods may be used to increase particle loading capacity of the balloon.

Abstract: The invention relates to new compounds for cancer therapy or diagnosis and more specifically to the use of a non-toxic B subunit of Shiga toxin mutant as a vector for diagnostic products or drugs in over-expressing Gb3 receptor cells, such compounds having the following formula: STxB-Z(n)-Cys-Y(m)-T wherein STxB is the Shiga Toxin B subunit or a functional equivalent thereof, Z(n) wherein n is 0 or 1 and when n is 1, Z is an amino-acid residue devoid of sulfhydryl group, or is a polypeptide, Cys is the amino-acid residue for Cysteine, T is a molecule linked by a covalent bound to the S part of Cys, selected in a group comprising: agents for in vivo diagnosis, cytotoxic agents, prodrugs, or enzymes for the conversion of a prodrug to a drug, Y(m) wherein m is 0 or 1 and when m is 1, Y is a linker between T and Cys, said linker being either cleavable or not cleavable for the release of T after the internalization of the hybrid compound into said cells.

Abstract: The present invention is directed to novel compositions and methods utilizing delivery agents comprising protein cages, medical imaging agents and therapeutic agents.

Abstract: The invention encompasses particles comprising metal atoms, methods of making the particles, and methods for using the particles. In particular, the particles may be used to image biological tissues or to deliver a bioactive agent.

Abstract: The invention provides compositions and method for delivering a therapeutic or diagnostic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically or diagnostically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic or diagnostic agent coupled to a Procaspase 8 polypeptide and a pharmaceutically acceptable carrier.

Abstract: Methods and compositions for diagnosis, prognosis and monitoring of ovarian cancer and lung cancer are provided. Assays that detect NHERF-I (or one or more markers related thereto) and NHERF-I-containing complexes are used to assign a diagnosis to a subject being assessed for the presence of ovarian or lung cancer; assign a prognostic risk to a subject suffering from ovarian or lung cancer; or monitor the course of ovarian or lung cancer treatment in a subject.

Abstract: A polypeptide or multimeric polypeptide construct having the ability to bind to cMet or a complex comprising cMet and HGF, and methods for use are disclosed.

Abstract: Disclosed are novel peptides that are useful, for example, for detecting target proteins having a ?-sheet secondary structure which may be associated with a disease, and for diagnosing and treating such a disease. Related methods and kits also are disclosed.

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 discloses methods and materials for delivering a cargo compound into a cancer cell. Delivery of the cargo compound is accomplished by the use of protein transduction domains derived from cupredoxins. The invention further discloses methods for treating cancer and diagnosing cancer.

Abstract: The present invention describes polymer nanoparticles with a cationic surface potential, in which both hydrophobic and hydrophilic pharmaceutically active substances can be encapsulated. The hydrophilic and thus water-soluble substances are encapsulated in the particle core by co-precipitation through ionic complexing with a charged polymer. Both therapeutic agents and diagnostic agents can be used as pharmaceutically active substances for encapsulation. The cationic particle surface permits stable, electrostatic surface modification with partially oppositely charged compounds, which can contain target-specific ligands for improving passive and active targeting.

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: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury.

Abstract: Methods of imaging a living host using Raman nanoparticles; methods of generating a true image of a living host having been administered Raman nanoparticles; methods of multiplex imaging of a living host using a plurality of Raman nanoparticles; methods of generating multimodality images by combining Raman images with other functional/anatomical images; labeled Raman nanoparticles; and the like, are provided.

Abstract: The present invention is directed to a method for preparing an anhydrous 18F-radiolabeled fluorinating agent by a nucleophilic reaction of a hydrated 18F-radiolabeled fluoride ion source with an unsaturated carrier compound; treating the 18F-radiolabeled carrier compound to produce a non-aqueous mixture of the 18F-radiolabeled carrier compound in a solvent; and reacting the 18F-radiolabeled carrier compound with a nucleophilic composition in a nucleophilic reaction to produce an anhydrous 18F-radiolabeled fluorinating agent. The present invention is also directed to an anhydrous 18F-radiolabeled fluorinating agent comprising the formula [QnM]x+(18F?)x. Additionally, the present invention is directed to an 18F-radiolabeled fluorinated radiopharmaceutical or an 18F-radiolabeled fluorinated radiotracer prepared by reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate.

Abstract: The present invention relates to endothelial cell-specific genes and encoded polypeptides and materials and uses thereof in the imaging, diagnosis and treatment of conditions involving the vascular endothelium.

Abstract: The present invention relates to biodegradable biocompatible polyketals, methods for their preparation, and methods for treating animals by administration of biodegradable biocompatible polyketals. In one aspect, a method for forming the biodegradable biocompatible polyketals comprises combining a glycol-specific oxidizing agent with a polysaccharide to form an aldehyde intermediate, which is combined with a reducing agent to form the biodegradable biocompatible polyketal. The resultant biodegradable biocompatible polyketals can be chemically modified to incorporate additional hydrophilic moieties. A method for treating animals includes the administration of the biodegradable biocompatible polyketal in which biologically active compounds or diagnostic labels can be disposed. The present invention also relates to chiral polyketals, methods for their preparation, and methods for use in chromatographic applications, specifically in chiral separations.

Abstract: A hydrogel coupling device for the transmission of ultrasound therethrough having a predetermined shape and comprising a hydrogen bonded composition comprising PVA, one or both of PVP and PEG, and the balance water. The predetermined shapes are formed and are then exposed to (a) one or more freeze/thaw cycles, (b) one or more dehydration/re-hydration cycles, or (c) one or more freeze/thaw cycles and one or more dehydration/re-hydration cycles. The shapes may further be irradiated with high energy radiation followed by heat treating.

Abstract: We describe a method for opening the blood-brain barrier (BBB) using ultrasound and preformed microbubbles. With this method, diagnostic or therapeutic agents may be administered to the brain. This method can open a focal region of the BBB and administer agents in a targeted fashion or the method can open large regions (or the entirety) of the brain for more global administration of agents. In one embodiment, the method can be used to administer contrast agents (e.g., agents that increase or decrease the magnetic resonance imaging signal) to the brain and thereby improve the quality or information content of imaging data. In another embodiment, a standard clinical diagnostic ultrasound scanner can be used to open specific regions of the BBB and administer diagnostic or therapeutic agents. Importantly, this invention can open the BBB in a non-destructive/non-invasive fashion, allowing the subject to be awake and suffer no detectable side effects.

Abstract: A system may include a means for administering a therapeutic agent to a subject; a means for administering a first pharmaceutically-acceptable taggant to the subject at least substantially concurrent with the therapeutic agent, the first pharmaceutically-acceptable taggant having a pharmacokinetic profile; and a means for administering a second pharmaceutically-acceptable taggant to the subject with the first pharmaceutically-acceptable taggant, the second pharmaceutically-acceptable taggant having a pharmacokinetic profile different from the pharmacokinetic profile of the first pharmaceutically-acceptable taggant.

Abstract: A system may include a means for administering a therapeutic agent to a subject; a means for administering a first pharmaceutically-acceptable taggant to the subject at least substantially concurrent with the therapeutic agent, the first pharmaceutically-acceptable taggant having a pharmacokinetic profile; and a means for administering a second pharmaceutically-acceptable taggant to the subject with the first pharmaceutically-acceptable taggant, the second pharmaceutically-acceptable taggant having a pharmacokinetic profile different from the pharmacokinetic profile of the first pharmaceutically-acceptable taggant.

Abstract: Nanoparticle-coated medical devices, nanoparticle-containing formulations and methods of using for treating a vascular disease are disclosed. The medical device includes a coating that comprises a plurality of nanoparticles, wherein the nanoparticles comprise one or more bioactive agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles and further comprise one or more contrast enhancing agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles.

Abstract: The invention provides PRSS23, which is associated with cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of PRSS23 as well as pharmaceutical compositions comprising such compounds. The invention also provides PRSS23 as a biomarker for diseases such as cardiovascular diseases, hematological diseases, neurological diseases, cancer, endocrinological diseases, and urological diseases.

Abstract: Gas-filled microvesicles comprising a boundary envelope containing a gas, wherein said microvesicles comprise: —a first component, bound to said envelope, having binding affinity for an Fc-region of an antibody; and—a second component comprising a Fc-region of an antibody, bound to said first component through said Fc-region, said second component comprising a targeting ligand or a therapeutic agent. Aqueous suspensions of said microvesicles are particularly useful in contrast enhanced ultrasound imaging.

Abstract: A method for detecting abnormal biological tissue includes administering a vasoactive agent and determining the rate of blood flow in a tissue of interest.

Abstract: The present invention relates to a method for preventing and/or treating visceral adiposity and/or to alter body fat distribution by administering a certain nutritional composition to a human subject with the age between 0 and 48 months, and preventing the occurrence of diseases later in life.

Abstract: Disclosed are pharmaceutical compounds comprising a cell-specific targeting moiety, an anti-cell proliferation moiety, and a chelator moiety. Also disclosed are methods for treating a subject with a hyperproliferative disease, methods for diagnosing presence of a hyperproliferative disease in a subject, and methods for detecting a therapeutic response in a subject that employ the pharmaceutical compounds of the present invention.

Abstract: The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages.