Abstract: Novel methods of synthesis of chelator-targeting ligand conjugates, compositions comprising such conjugates, and therapeutic and diagnostic applications of such conjugates are disclosed. The compositions include chelator-targeting ligand conjugates optionally chelated to one or more metal ions. Methods of synthesizing these compositions in high purity are also presented. Also disclosed are methods of imaging, treating and diagnosing disease in a subject using these novel compositions, such as methods of imaging a tumor within a subject and methods of diagnosing myocardial ischemia.

Abstract: The present invention relates to the use of polymers as contrast agents for ultrasounds. The idea is to have a molecular imprint in the polymer that is specific for a given molecule or analyte. When that molecule binds to the polymer it induces a conformational change that results in an increase in the ultrasound signal, referred to as a target-bound state. The method can also be used for example for quantitative measurements of analytes.

Abstract: The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

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: Agents and methods for imaging a cell and/or a portion of tissue characterized by fibrosis, as well as to agents and methods for determining and/or diagnosing fibrotic diseases are disclosed herein. Also disclosed herein are polymer conjugates that can include a detectable label, a retinoid and a polymer. The polymer conjugates can be used to image a portion of tissue, deliver a detectable label to a portion of tissue or a cell and/or diagnosis a condition or disease.

Abstract: The present invention discloses methods and materials for delivering a cargo compound into a brain cancer cell and/or across the blood-brain barrier. Delivery of the cargo compound is accomplished by the use of protein transport peptides derived from Neisseria outer membrane proteins, such as Laz. The invention also provides synthetic transit peptides comprised of the pentapeptide AAEAP. The invention further discloses methods for treating cancer, and specifically brain cancer, as well as other brain-related conditions. Further, the invention provides methods of imaging and diagnosing cancer, particular brain cancer.

Abstract: A method for generating stable encapsulated bubbles and dried encapsulated bubbles comprises introducing an inner stream of a gas into a liquid-filled chamber from an exit orifice of a capillary tube; introducing a middle stream of a water immiscible liquid into the exit orifice; and introducing an outer stream of an aqueous liquid to the exit orifice, to form compound bubbles. The encapsulated bubbles are formed after converting the middle phase of compound bubbles into a shell. The stable encapsulated bubbles or the stable dried encapsulated bubbles can be used in drug delivery and for enhancing ultrasound imaging.

Abstract: Disclosed are humanized antibodies that bind specifically to TNF superfamily member 15 (TNFSF15), also known as TL1A. Methods of making and using the anti-TL1A antibodies are also described. The humanized antibodies may be antagonists and may used to treat or diagnose conditions associated with TL1A function.

Abstract: An ultrasound contrast agent composed of at least one kind of low-boiling water-insoluble substance (with a boiling point lower than 37° C.) and at least one kind of high-boiling water-insoluble substance (with a boiling point higher than 37° C.). The former vaporizes to absorb ultrasonic energy upon application of ultrasound, thereby causing the latter to vaporize secondarily, with the resulting bubbles producing an echo image. It is less liable to bumping and hence safe.

Abstract: The present invention relates to the detection of traumatic brain injury by detecting A? protein aggregates associated with traumatic brain injury. These A? protein aggregates are detected using peptide and peptide mimic probes that preferentially associate with A? protein aggregates associated with traumatic brain injury.

Abstract: The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

Abstract: Compositions and methods for dual imaging and for dual chemotherapy and radiotherapy are disclosed. More particularly, the invention concerns compounds comprising the structure X1—Y—X2, wherein Y comprises two or more carbohydrate residues covalently attached to one another, X1 and X2 are diagnostic or therapeutic moieties covalently attached to Y, provided that when Y does not comprise a glucosamine residue, X1 and X2 are diagnostic moieties. The present invention also concerns methods of synthesis of these compounds, application of such compounds for dual imaging and treatment of hyperproliferative disease, and kits for preparing a radiolabeled therapeutic or diagnostic compound.

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: Provided is a particle-stabilized ultrasound contrast agentn (UCA) and methods of preparing same. Also provided is a method for preparing a lyoprotected UCA, a freeze-dried lyoprotected UCA, and a reconstituted freeze-dried lyoprotected UCA.

Abstract: The disclosure provides, in part, a method for quantifying cell numbers in vivo. The disclosure comprises a method of quantifying labeled cells by nuclear magnetic resonance techniques and a computer method for the same.

Abstract: The present invention provides compositions and methods useful for diagnostic and imaging techniques for detecting and localizing the biomarker Plectin-1. The present invention provides multimeric peptide ligand complexes for targeting Plectin-1, such as the multimeric peptide ligand complex having the formula (?AKTLLPTPGGS(PEG5000))4 KKKKDOTA?A-NH2, to which imaging agents and/or therapeutic agents can be conjugated.

Abstract: The present invention relates to Her3 specific antibodies, preferably fully human or humanized antibodies and antigen-binding portions thereof. Nucleic acid molecules encoding the Her3 antibodies as well as methods of use thereof are also disclosed. Also included are pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for treatment and diagnosis of pathological hyperproliferative oncogenic disorders associated with aberrant expression of Her3 or Her2 including aberrant activation of each of these receptors.

Abstract: Nanocarriers and methods of preparation and use of nanocarriers are presented. In some embodiments, a nanocarrier composition comprises an organic liquid comprising a plurality of nanoparticles dispersed therein; and a coating material disposed around the exterior surface of the organic liquid. Biological tissue may be imaged or treated by coming into contact with a nanocarrier composition, and, at least in some embodiments, irradiated.

Abstract: PSMA ligands, compositions, and methods therefore are disclosed where the ligand is a peptide having the sequence X1X2CVEVX3QNSCX4X5 where X1-X5 are independently a natural or non-natural amino acid or a peptide having the sequence CALCEFLG [SEQ ID NO: 1]. Especially preferred aspects include diagnostic reagents for detection and/or quantification of PSMA in a sample, therapeutic reagents, and diagnostic imaging reagents.

Abstract: Compositions comprising a tripeptide having the sequence XC1C2; wherein X is any amino acid such that XC1C2 is capable of binding a metal in a square planar orientation or square pyramidal orientation or both; and wherein C1 and C2 are the same or different; and wherein C1 and C2 individually are chosen from a cysteine and a cysteine-like nonnatural amino acid, as well as metal-XC1C2 complexes and methods for forming such complexes.

Abstract: Compositions comprising a tripeptide having the sequence XC1C2; wherein X is any amino acid such that XC1C2 is capable of binding a metal in a square planar orientation or square pyramidal orientation or both; and wherein C1 and C2 are the same or different; and wherein C1 and C2 individually are chosen from a cysteine and a cysteine-like nonnatural amino acid, as well as metal-XC1C2 complexes and methods for forming such complexes.

Abstract: The present invention includes arginase enzyme inhibitors, compositions comprising these arginase inhibitors, and methods of treating or diagnosing conditions characterized either by abnormally high arginase activity or abnormally low nitric oxide levels in a mammal, comprising administering compositions of the invention to the mammal.

Abstract: Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A—X—B—C)n—M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

Abstract: The invention features sincalide formulations that include an effective amount of sincalide, a bulking agent/tonicity adjuster, a stabilizer, a surfactant, a chelator, and a buffer. The invention also features kits and methods for preparing improved sincalide formulations as well as methods for treating, preventing, and diagnosing gall bladder-related disorders using sincalide formulations.

Abstract: The present invention describes processes for the preparation of a lipid blend and a uniform filterable phospholipid suspension containing the lipid blend, such suspension being useful as an ultrasound contrast agent.

Abstract: The invention relates to an emulsion that can be activated by ultrasounds, comprising, in an emulsion in an aqueous solution, microparticles having a diameter of less than 10 ?m and containing an active agent and a gaseous precursor in a liquid form, encapsulated by a first emulsifier. The microparticles contain nanoparticles smaller than 1 ?m, in an emulsion in the gaseous precursor, each nanoparticle comprising an inner liquid that contains the active agent and is encapsulated by a second emulsifier.

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: 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: The disclosure provides, in part, fluorocarbon imaging reagents and formulations for the ex vivo labeling of cells. Labeled cells may be detected in vivo or ex vivo by a nuclear magnetic resonance technique, such as magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS). The disclosure additionally provides methods for using the imaging reagents in a variety of clinical procedures.

Abstract: A skin marker for providing a reference point for a plurality of different medical imaging procedures, said marker incorporating one or more substances having one or more of radiance and/or hydration and/or radiopaque and/or radio luminescent and/or radioactive properties for detection by X-ray and/or Computer Tomography (CT) and/or MRI and/or Ultrasonic scanning processes and/or Positron Emission Tomography (PET), and one or more markings recognisable by an optical imaging process such as 3D surface scanning.

Abstract: Disclosed is a method for monitoring early treatment response of a cancer treatment comprising measuring by magnetic resonance spectroscopy (MRS), for example, proton MRS, the amount of Choline present in the endomembranes of the cancerous tissue before and after treatment; the treatment comprises administration of a cytotoxic therapy, whereby a decrease in the amount of Choline after treatment is indicative of a positive response. The decrease in the amount of Choline represents the decrease in the internal cell membrane as a result of down regulation of the organelles and their secretory granules and their transport vesicles. Disclosed also is a method for determining effectiveness of a cytotoxic treatment of cancer. In addition, a method for monitoring protein translation related to the cytotoxic treatment of cancer is disclosed.

Abstract: Methods and suspensions are provided that are useful for preparing readily reconstitutable, dry compositions of micro- or nanospheres. The dry compositions find use in diagnostic applications such as ultrasonic imaging. The suspension includes as key ingredients one or both of t-butyl alcohol and/or an amorphous sugar (or mixture of amorphous sugar) in specified amounts that reduce aggregation of the particles comprising the suspension.

Abstract: The invention is directed to analogs of LHRH-II and, more generally, to analogs of the LHRH family in which modifications have been made that confer enhanced binding affinity for LHRH receptors and/or improved metabolic stability. The invention is further directed to methods of targeted therapy and targeted imaging in patients with sex-hormone-related cancers or other LHRH-mediated diseases.

Abstract: Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an alkene or alkyne dienohile.

Abstract: Disclosed are SPARC and albumin binding peptides for the targeting of disease sites, such as tumors, with therapeutic and diagnostic agents In particular, compositions comprising SPARC binding peptide—Antibody Fc domain fusion proteins and methods of their use are disclosed.

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: The present invention relates to methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using a benzofuran compound or its radioisotope derivatives. In one embodiment a method of myelin detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the benzofuran compound, or a derivative of the compound, and determining myelination in the subject by detecting binding in the sample. In one embodiment, the invention provides a method of imaging myelinated tissue in a surgical field of mammalian tissue comprising the steps of contacting the surgical site with the benzofuran compound or a radioisotope derivative of the compound, and detecting binding in the surgical site.

Abstract: The present invention describes processes for the preparation of a lipid blend and a uniform filterable phospholipid suspension containing the lipid blend, such suspension being useful as an ultrasound contrast agent.

Abstract: This disclosure generally relates to methods useful for improving, for example, blood vessel density and/or blood vessel patency to a tissue by administration of a hedgehog pathway inhibitor. In certain embodiments, the hedgehog pathway inhibitor is administered with an agent to improve the delivery of the agent to the tissue. In certain embodiments, the tissue comprises tumor tissue.

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 invention provides compositions and methods 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 an albumin binding peptide and a pharmaceutically acceptable carrier.

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: A nano-capsule construct for imaging and therapeutic uses and method for production are provided. One nano-probe embodiment based on genome-depleted plant brome mosaic virus (BMV) whose interior is doped with indocyanine green (ICG), an FDA-approved near infrared fluorescent dye, is used to illustrate the invention. The material encapsulated in viral shell components may be coated with functionalized coatings such as branched, dendritic polymer coatings to improve longevity and distribution in the body as well as antibody conjugation for increased target specificity. The constructs can also be coated with ferromagnetic iron oxide nanoparticles, enabling the ICG-containing capsules to be used as nano-probes with the capability of being detected in both optical and magnetic resonance imaging. The capsules may be produced by purifying a plant or animal viruses and disassembling the viruses to provide virus shell components.

Abstract: L-cells may be introduced in the gastrointestinal tract. L-cells are used in the digestive process to produce a more efficient and lasting means of regulating feelings of satiation in a patient. Desired metabolic effects may be achieved by manipulating L-cells via delivery sites, frequency of delivery, or type of biological substance delivered.

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 application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

Abstract: One aspect of the present invention relates to a method of ultrasonography, utilizing a gel comprising a reverse phase polymer which facilitates the transmission of high-frequency sound waves. Further, the inherent properties of the reverse phase polymer result in increased adhesion at higher temperatures, thereby helping to maintain the desired position of the ultrasound probe until the user intends to adjust the probe's position. In certain embodiments, the method is utilized in a medical procedure in which stability of an ultrasound probe or transducer in an intended desired position can improve the outcome or increase the efficiency of the procedure. In certain embodiments, the gel further comprises an additive to increase the ultimate adhesion of the gel. In still other embodiments, the gel can be used on the skin, on a protective sheath encasing an ultrasound probe, or between the sheath and the probe, or any or all of them.

Abstract: Disclosed herein is a class of linkable tetrasaccharide compounds that includes the amino phenyl glycoside of sialyl Lewis X (SLeX) and related analogs. These compounds have conjugatable nucleophilic groups, making them useful in preparing multimeric SLeX compositions. In particular, the disclosed SLeX compounds can be used to prepare selectin binding ligand con-jugatcs by linking them to a reporter moiety, such as a contrast agent, a radiodiagnostic agent, or a cytotoxic or chemotherapeutic agent. The SLeX compounds and conjugates of the invention exhibit binding to selectin that is similar to native Sialyl LeX, and are, therefore, useful for diagnosing and treating selectin-mediated disorders and related conditions.

Abstract: The present invention provides humanized, chimeric and human anti-alpha-fetoprotein antibodies, fusion proteins, and fragments thereof. The antibodies, fusion proteins, and fragments thereof, as well as combinations with other suitable antibodies, are useful for the treatment and diagnosis of hepatocellular carcinoma, hepatoblastoma, germ cell tumors carcinoma and other AFP-producing tumors.

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.