Abstract: The compositions and methods described herein relate generally to therapeutic compositions containing Nerium species extracts, as well as to methods for treating diseases or disorders by administering the compositions, including compositions having a combination of Nerium species extract and glutathione. It further includes pharmaceutical compositions containing a combination of glutathione and a Nerium species extract. The compositions and methods disclosed may be useful for treating a variety of diseases or disorders including one or more cell-proliferative diseases or disorders, infections, and dementias.

Abstract: In one or a plurality of embodiments, there is provided a target molecule of amylospheroid, which is expressed in mature neurons and to which the amylospheroid binds to induce death of cells. Further, in one or a plurality of embodiments, there is provided a method and a substance for inhibiting death of mature neurons induced by the amylospheroid. In one aspect, the present disclosure relates to a use of Na+/K+-ATPase ?3 as a binding target molecule of amylospheroid. In another aspect, the present disclosure relates to a method for suppressing death of mature neurons induced by the amylospheroid, including inhibiting protein-protein interaction between the amylospheroid and the Na+/K+-ATPase ?3, and the like.

Abstract: The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use for 18F imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited to 18F labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

Abstract: The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.

Abstract: The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic agent is pulmonary embolus.

Abstract: Transglutaminase inhibitors and methods of use thereof are provided.

Abstract: This invention relates to methods for evaluating the efficacy of an IGF1R inhibitor, such as an anti-IGF1R antibody, for the treatment of an Ewing's sarcoma tumor by determining the level of tumoral glucose metabolism. Tumoral glucose metabolism is determining at an early point in the treatment regimen by any of several methods known in the art including FDG-PET/CT scan.

Abstract: The invention in suitable embodiments is directed to an isolated protein comprising one or more amino acid sequences, each amino acid sequence capable of being functionalized and/or attached in whole and/or in part to one or more or a plurality of elements of one or more types including to cargo elements, forming a composition of elements suitable for use as an in vivo and/or in vitro medicament to treat one or more biological species.

Abstract: The invention described herein provides for human antibodies produced in non-human animals that specifically bind to Pseudomonas aeruginosa Lipopolysaccharide (LPS). The invention further provides methods for making the antibodies in a non-human animal, expression of the antibodies in cell lines including hybridomas and recombinant host cell systems. Also provided are kits and pharmaceutical compositions comprising the antibodies and methods of treating or preventing pseudomonas infection by administering to a patient the pharmaceutical compositions described herein.

Abstract: 99mTc-labeled triphenylphosphonium contrasting agents that target the mitochondria and are useful for early detection of breast tumors using scintimammographic imaging. 99mTc-Mito10-MAG3 possesses advantageous radiopharmaceutical properties. The uptake in the myocardium is reduced by one to two orders of magnitude compared to 99mTc-MIBI. 99mTc-Mito10-MAG3 exhibits fast blood clearance, with a blood half-life of less than 2 minutes in rats. A diminished myocardial uptake combined with a prompt reduction of cardiovascular blood pool signal to facilitate improved signal-to-background ratios.

Abstract: The present invention relates to imaging agent compositions comprising radiolabelled c-Met binding peptides suitable for positron emission tomography (PET) imaging in vivo. The c-Met binding peptides are labelled with the radioisotope 18F. Also disclosed are pharmaceutical compositions, methods of preparation of the agents and compositions, plus methods of in vivo imaging using the compositions, especially for use in the management of cancer.

Abstract: The present invention relates to novel 5-pyrrolidinylsulfonyl isatin derivatives, non-peptidyl Caspase binding Radioligands (CbRs) and CbR-transporter conjugates derived from said isatin derivatives, diagnostic compositions comprising said compounds of the invention and their use for non-invasive diagnostic imaging.

Abstract: Metal chelators of Formula I and Formula II are disclosed: or a pharmaceutically acceptable salt thereof. Also disclosed are metal chelator-targeting moiety complexes, metal chelator-targeting moiety-metal conjugates, kits, and methods of their preparation and use in diagnosis and/or treatment of diseases and conditions, including, inter alia, cancer and thrombosis.

Abstract: The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.

Abstract: A cell permeable probe is disclosed. The cell permeable probe includes a cell membrane translocating element, which facilitates transport of the probe into the intracellular component of a cell. The cell permeable probe may also include a plurality of binding moieties for a disease specific marker and a contrast agent.

Abstract: The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.

Abstract: A chelation structure and method of forming and using the chelation structure. The chelation structure has a backbone that includes a linear sequence of monomeric backbone units, at least one polymer side chain, and at least one chelator side chain. The side chains are each covalently coupled to the backbone at one of the monomeric backbone units by a bond that is independently biodegradable or non-biodegradable. The chelation structure is synthesized by Radical Addition Fragmentation Transfer (RAFT), Atom Transfer Radical Polymerization (ATRP), or Free Radical Polymerization (FRP). The chelation structure, individually or in combination with a shuttle chelator, may be introduced into a mammal to bind an amount of a substance in a mammal, the substance being at least one of a metal and heme. The chelation structure has a log stability constant exceeding that of the shuttle chelator for binding the substance within cells of the mammal.

Abstract: The present invention provides compounds, compositions, and methods for detecting, diagnosing and treating cancers such as glioblastoma multiforme.

Abstract: Methods and compositions for diagnosing, staging disease, monitoring therapeutic effect of drugs and imaging a patient are provided, including radiopharmaceutical formulations. Compositions comprising Ga-AMBA complexed with a radioactive isotope are provided; as are methods of imaging Gastrin Releasing Peptide receptor (GRP-R) bearing tissue and methods of diagnosing or staging disease in patients suspected of having disease associated with aberrant GRP-R function. Further, methods of monitoring therapeutic effect of a drug targeted to a receptor that crosstalks with GRP-R are provided; as are methods of pre-dosing/co-dosing non-target tissues containing GRP-R.

Abstract: The present invention relates to 99mTc-maraciclatide radiopharmaceutical compositions, which are stabilised with a radioprotectant. Also described are kits for the preparation of the radiopharmaceutical compositions, as well methods of preparing such compositions from the kit. The invention also includes methods of imaging the mammalian body using the radiopharmaceutical compositions.

Abstract: The present invention, among others, relates to a compound having a structure according to formula (I) or a pharmaceutically acceptable salt thereof, wherein Xaa1 to Xaa4 are independently of each other, an optionally N-alkylated natural or unnatural amino acid, R is H or methyl, L is a linker moiety, Ar is a spacer comprising an aromatic moiety, and D comprises, preferably is i) a combination of an organic complexation agent and a detectable label; or ii) a detectable label, an organic complexation agent or an active substance, said active substance particularly being selected from cytotoxic agents, lipids, sugars, sugar conjugates, sugar derivatives, proteins and combinations thereof, with the proviso that -L-Ar-D does not comprise a 18F-benzoyl residue.

Abstract: Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH2—SO3H)COOH or Arg-Gly-NH—CH(CH2—SO3H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting integrins including but not necessarily limited to ?5?1-Integrin, ?v?3-Integrin and ?v?5-Integrin, inhibiting cellular adhesion to RGD binding sites, preventing or treating viral or other microbial infections, inhibiting angiogenesis in tumors, retinal tissue or other tissues or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.

Abstract: The invention relates to conjugates of formula (V) or (VI), their use as radiopharmaceuticals, processes for their preparation, and synthetic intermediates used in such processes.

Abstract: Methods and compositions are provided for improving tissue growth and device integration in vivo. Substrates and devices coated with an ?2?1 or ?5?1 integrin-specific ligand are provided. The substrates and devices coated with an ?2?1 or ?5?1 integrin-specific ligand are shown to have greater tissue formation on the surface relative to controls, in particular greater bone formation.

Abstract: New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.

Abstract: The invention provides methods of targeting atherosclerotic plaques using LyP-1 related peptides. The invention additionally provides methods of treating an inflammatory condition using LyP-1 related peptides.

Abstract: Tracers comprising an oligopeptide comprising a fragment of a natriuretic peptide, wherein the fragment comprises the sequence Arg-Ile-Asp-Arg-Ile (SEQ ID NO.: 1), and a signaling moiety, are disclosed. Further disclosed are methods of imaging atherosclerotic plaque by PET scanning or MRI using a tracer.

Abstract: Cancers are extremely heterogeneous in terms of the frequency and types of mutations present in different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. Multiple, unique small peptides bind to cell lines derived from different colon adenocarcinomas. Within two hours of contact, the colorectal cancer cells are able to transfer a 32P radioisotope from the small peptides to cellular proteins; the transfer occurs at a substantially higher rate than in the colorectal cancer cells than in cell lines derived from other cancers or from normal tissues.

Abstract: A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.

Abstract: The invention relates to peptide derivatives (peptides and pseudo-peptides) and the use thereof as vectors for molecules of interest. The invention also relates to conjugates containing a peptide derivative of the invention bound to a molecule of interest. The peptides of the invention can be used, in particular, to vectorize, generally in the form of prodrug conjugates, molecules of pharmaceutical or diagnostic interest such as, for example, therapeutic molecules, imaging or diagnostic agents, or molecular probes, across cell membranes of different tissues or organs, healthy or pathologic, and in particular to enable their transport across physiological barriers of the nervous system such as the Blood brain barrier (BBB), Blood-spinal cord barrier (BSCB), or Blood-retinal barrier (BRB).

Abstract: Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

Abstract: The present invention relates to labelled cMet binding peptides suitable for optical imaging in vivo. The peptides are labelled with a benzopyrylium dye suitable for imaging in the red to near-infrared region. Also disclosed are pharmaceutical compositions and kits, as well as in vivo imaging methods, especially of use in the detection, staging, diagnosis, monitoring of disease progression or monitoring of treatment of colorectal cancer (CRC).

Abstract: The present invention features noninvasive methods for diagnosing IgA or IgM kidney disorders, such as IgA nephropathy, Henoch-Schönlein purpura, and IgM nephropathy, in a mammal. The invention also features compositions and kits useful in diagnosing these disorders.

Abstract: In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-1 receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role.

Abstract: The present invention relates to novel muteins derived from human lipocalin 2 (hNGAL) and related proteins that bind a given non-natural ligand with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates a method for producing such a mutein. Furthermore, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer, said methods comprising the step of administering to a subject a dose comprising an amount of radioactively labeled L70, N-[4-[[[[[4,7,10-Tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetyl]amino]acetyl]amino]benzoyl]-L-glutaminyl-L-tryptophyl-L-alanyl-L-valyl-glycyl-L-histidyl-L-leucyl-L-methioninamide.

Abstract: Disclosed herein are compounds that inhibit Hsp90 interactions with IAP proteins, such as Survivin, XIAP, cIAP1, or cIAP2, and methods for identifying and using such compounds.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>linker1)k-[{<bd1>-linker2-<bd2>linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: Methods and compositions are described for classifying cells and/or peptides that associate or bind with a particular characteristic pattern to a plurality of cells or cell lines. Aspects of the invention also include the use of peptide(s) having an appropriate binding characteristic to deliver a drug to a cell or cell population.

Abstract: New and improved compounds for use in radiodiagnostic imaging or radiotherapy having the formula M-N—O—P-G, wherein M is the metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy to a patient using the compounds of the invention are also provided. A method for preparing a diagnostic imaging agent from the compound is further provided. A method for preparing a radiotherapeutic agent is further provided.

Abstract: The invention relates to radiodiagnostic and radiotherapeutic agents, including biologically active vectors labelled with radionuclides. It further relates to methods and reagents labelling a vector such as a peptide comprising reaction of a compound of formula (I) with a compound of formula (II): R*-L2-C?N+—O???(II) or, a compound of formula (III) with a compound of formula (IV) in the presence of a Cu (I) catalyst. The resultant labelled conjugates are useful as diagnostic agents, for example, as radiopharmaceuticals more specifically for use in Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) or for radiotherapy.

Abstract: The present invention encompasses an antithrombotic nanoparticle.

Abstract: The present invention relates to tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment (radiotherapy) of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives of the present invention has a high subnanomolar affinity to integrin ?v?3 (also called as a vitronectin receptor) that is activated in an angiogenic action induced by a tumor, reflects a high tumor image of the tricatvonyl technetium-99m labeled cyclic RGD derivative after initial intake in an animal in which cancer cells are transplanted, and acts exclusively upon cancer cells having selectively activated integrin ?v?3 because of a substantially low intake into the liver and intestines, compared to existing known radioactive isotope labeled cyclic RGD derivatives.

Abstract: Tumor targeting peptides and uses thereof in tumor diagnosis and treatment.

Abstract: The invention encompasses radiopharmaceutical compounds that can be used in imaging cell death associated with either apoptosis or necrosis. Phosphatidylethanolamine (PtdE) is externalized to the surface of apoptotic cells, and also becomes accessible in necrotic cells due to compromised plasma membrane integrity. Duramycin, a 19 amino acid polypeptide, binds PtdE at a 1:1 ratio with high affinity and exclusive specificity. Novel Duramycin-based radiopharmaceuticals and non-radioactively labeled compounds are disclosed herein. Such compounds facilitate detection of cell apoptosis and/or necrosis by binding to PtdE. The location of the bound compound can then be pinpointed using standard imaging techniques.

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: 99mTc-labeled triphenylphosphonium contrasting agents that target the mitochondria and are useful for early detection of breast tumors using scintimammographic imaging. 99mTc-Mito10-MAG3 possesses advantageous radiopharmaceutical properties. The uptake in the myocardium is reduced by one to two orders of magnitude compared to 99mTc-MIBI. 99mTc-Mito10-MAG3 exhibits fast blood clearance, with a blood half-life of less than 2 minutes in rats. A diminished myocardial uptake combined with a prompt reduction of cardiovascular blood pool signal to facilitate improved signal-to-background ratios.

Abstract: The present invention relates to a method for producing a polypeptide.

Abstract: The present invention relates to novel modified fatty acid analogs, where a positron or gamma-emitting label is placed at a position on a fatty acid backbone and an organic substituent is substituted at the 2,3; 3,4; 4,5; 5,6 and other sequence positions of a fatty acid backbone. These novel fatty acid analogs are designed to enter the tissues of interest by the same long chain fatty acid carrier mechanism as natural fatty acids, however, functional substituents in the 2,3; 3,4; 4,5; 5,6 and other sequence positions, block the catabolic pathway, thus trapping these analogs in a virtually unmodified form in the tissues of interest.