Abstract: The present invention provides a 99mTc-tetrofosmin radiopharmaceutical composition comprising tetrofosmin and a radioprotectant at a particular range of molar ratios. A kit and a multi-dose kit for the preparation of the radiopharmaceutical composition of the invention are also provided, as well as a process for the preparation of multiple unit patient doses of the radiopharmaceutical composition and a unit dose of the radiopharmaceutical composition.

Abstract: A molecular probe for labeling myelin includes a fluorescent stilbenzene derivative.

Abstract: One aspect of the present invention relates to a method of preparing radiofluorinated substituted alkyl, cycloalkyl, aryl, and alkenyl compounds. In a preferred embodiment, potassium fluoride-18 is used. Another aspect of the invention relates to piperazine compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the piperazine compounds contain a quaternary amine. Another aspect of the invention relates to arylphosphonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the phosphonium compound is a tetraaryl phosphonium salt. Another aspect of the present invention relates to a method of obtaining a positron emission image of a mammal, comprising the steps of administering to a mammal a compound of the invention, and acquiring a positron emission spectrum of the mammal.

Abstract: The present invention relates to methods for imaging annulus fibrosus tissue and a quantitative measurement of its local concentration in a sample using an agent comprising the compound of Formula I, a 13C or 2H enriched compound of Formula I, an 19F-labeled derivative of Formula I, a metal-DOTA (1,4,7,10-tetra-azacyclododecane-N,N?,N?,N??-tetraacetic acid) complex of Formula I, or a radioisotope derivative of Formula I.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patent who is then diagnosed or treated using the effector molecule.

Abstract: This document provides methods and materials related to hydroxyapatite particles. For example, hydroxyapatite particles, methods for making hydroxyapatite particles, and methods for using hydroxyapatite particles are provided herein.

Abstract: The present invention relates to a novel delivery system for delivering therapeutic agents into living cells, and more particularly, to novel chemical moieties that are designed capable of targeting and/or penetrating cells or other targets of interest and further capable of binding therapeutic agents to be delivered to these cells, and to delivery systems containing same.

Abstract: The present invention describes a newly discovered polynucleotide encoding a protein involved in the cell signaling cascade, called RET16, cloned, isolated and identified from TNF-alpha stimulated human microvascular endothelial cells, as well as mouse and rat RET16 orthologs thereof. Also described are the RET16 polypeptide sequence, expression vectors, host cells, agonists, antagonists, antisense molecules, and antibodies related to the polynucleotide and/or polypeptide of the present invention. Methods for screening for modulators, particularly inhibitors, of the human RET16 protein, and use of the RET16 polynucleotide and polypeptide for therapeutics and diagnostics are described.

Abstract: Compounds of formula (I) in salt or zwitterionic form, wherein R1, R2, R3, R4 and R5 have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

Abstract: The invention provides immunomodulatory compounds and methods for immunomodulation of cells and individuals using the immunomodulatory compounds.

Abstract: The present invention provides compounds, pharmaceutical compositions, and methods that can be used to treat pathologies that are due to copper overload or to the presence of reactive oxygen species.

Abstract: To provide a method of rapid methylation of alkenes, which is applicable to the preparation of a PET tracer and which enables alkenes to be methylated through cross coupling between SP2 (alkenyl) and SP3 (alkyl) carbon atoms rapidly and in a high yield. Methyl iodide and an alkenyltrialkylstannane are subjected to cross coupling in an aprotic polar solvent in the presence of a palladium complex having a valence of 0, a phosphine ligand, a cuprous halide, and a carbonate and/or alkali metal fluoride.

Abstract: Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

Abstract: The present invention is directed to surface functionalization of polymeric fibers. Surface biofunctionalization is achieved by covalent conjugation of biofunctional igands and/or cell growth factors that are crucial for cell attachment, proliferation and functions. Biofunctional fibers could be fabricated into three-dimensional scaffolds. Polymer fibers described here comprise of biocompatible polymers that are either biodegradable ornon-biodegradable. This patent also describes a series of new biodegradable polyphosphoramidates for the processing of biodegradable fibers. Scaffolds made of non-biodegradable functional fibers could be used for in vitro cell culture (for example, ex vivo cell expansion), while biodegradable functional fibers could be fabricated into tissue engineering scaffolds.

Abstract: Novel compositions and methods are provided for identifying agents which affect chromosomal stability and aging.

Abstract: The invention provides cobalamin compounds linked to a neutron capture therapy target (e.g. Boron-10 or Gadolinium-157), and optionally linked to a detectable moiety, as well as pharmaceutical compositions comprising the compounds, and methods for using the compounds in medical diagnosis and therapy.

Abstract: The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.

Abstract: The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.

Abstract: The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

Abstract: A process for diagnostic imaging of heart or adrenal glands of a human being comprises administering to the human being a radiopharmaceutical containing as an active ingredient a technetium-99m nitride heterocomplex comprising technetium-99m nitride and two different ligands coordinated therewith, i.e., a bisphosphinoamine compound and a bidentate ligand and represented by the formula (1): [99mTc(N)(PNP)(XY)]+. In this formula, 99mTc(N) is technetium-99m nitride, PNP is a bisphosphinoamine compound and XY is a bidentate ligand as described in the specification. The compound of the formula is markedly accumulated in heart and adrenal glands and hence is used for radiodiagnostic imaging of heart and adrenal glands.

Abstract: The present invention provides radioactive metal heterocomplexes of formula (I): [(Me=N—R)L1L2]+Z? (I), wherein Me, R, L1 L2 and Z? have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me=N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me=N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me=N—R)L1L2]+ Z?heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.

Abstract: The present invention is directed to a series of new polycationic biodegradable polyphosphoramidates. Process for making the polymers, compositions containing these polymers and bioactive ligands to enhance the cellular uptake ad intracellular trafficking, articles and methods for delivery of drugs and genes using these polymers are described. A gene delivery system based on these polymers is prepared by complex coacervation of nucleic acid (DNA or RNA) with polymers. Targeting ligands and molecules that could facilitate gene transfer can be conjugated to polymers to achieve selective and enhanced gene delivery. The current invention also provides a complex composition with buffering capacity.

Abstract: The use of a selective chemical and bioorthogonal reaction providing a covalent ligation such as the Staudinger ligation, in targeted molecular imaging and therapy is presented, more specifically with interesting applications for pre-targeted imaging or therapy. Current pre-targeted imaging is hampered by the fact that it relies solely on natural/biological targeting constructs (i.e. biotin/streptavidin). Size considerations and limitations associated with their endogenous nature severely limit the number of applications. The present invention describes how the use of an abiotic, bio-orthogonal reaction which forms a stable adduct under physiological conditions, by way of a small or undetectable bond, can overcome these limitations.

Abstract: The present invention provides radioactive metal heterocomplexes of formula (I): [(Me?N—R)L1L2]+Z (I), wherein Me, R, L1 L2 and Z? have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me?N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me?N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me?N—R)L1L2]+Z? heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.

Abstract: Compounds useful for associating with nanoparticle or microparticle emulsions to obtain magnetic resonance images permit control of the relaxivity of the signal and readily associate with the particulate components.

Abstract: The present invention is directed to compositions and methods of making and using compositions that are useful for treating cells or conditions caused or exacerbated by cell survival mechanisms of the body, particularly conditions exacerbated by cell survival mechanisms involving NF-KB. The compositions and methods of the present invention comprise a sensitizing agent or a chemopotentiating agent. In this regard, cobalamin drug conjugates and NO donors act as chemopotentiating agents. Nitrosylcobalamin is particularly useful as a sensitizing or chemopotentiating agent, and methods utilizing nitrosylcobalamin prior to, simultaneous with and subsequent to radiation or chemotherapy are described, as are compositions which first release a nitrosylcobalamin compound or biologically active analog thereof, and then release the chemotherapeutic agent. Nitrosylcobalamin itself is a chemotherapeutic, and when administered in conjunction with other anti-cancer agents or techniques, a synergistic effect is seen.

Abstract: Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described: and pharmaceutically acceptable prodrugs and salts thereof.

Abstract: Novel compositions and methods are provided for identifying agents which affect chromosomal stability and aging.

Abstract: A method of simply and quickly determining ?-ray releasing nuclides having long half-life without carrying out a chemical separation is provided. By inputting a data of pulses incident to an ?-ray detector in a computer, obtaining time distribution of the incident pulses by using a very short time measuring timer and plotting, and fitting the linear originated in a random event corresponding to the background and the non-linear originated in the correlated events of parent nuclides-progenies by using the least squares method, the whole generating probability P (t) from the parent nuclide to the progeny thereof is obtained. By subtracting the random events portion from the P(t), the correlated events portion is extracted. The radioactivity per unit can be obtained by dividing the extracted correlated events portion by the measured time, the amount of the supplied sample and the counting efficiency.

Abstract: The invention provides compounds having increased or reduced immunostimulatory effect, said compounds comprising a CpG dinucleotide and an immunomodulatory moiety wherein the increased or reduced immunomodulatory effect is relative to a similar compound lacking the immunomodulatorv moiety.

Abstract: The invention provides methods for modulating the immune response caused by CpG dinucleotide-containing compounds. The methods according to the invention enables both decreasing the immunostimulatory effect for antisense applications, as well as increasing the immunostimulatory effect for immunotherapy applications.

Abstract: The invention provides a series of lipophilic phosphonium cations (PhCs) labeled with 18F for non-invasive assessment of ??m, lipophilic ammonium cation analogs of the PhCs, and methods of using same for imaging and detection of mitochondrial-related pathologies in patients using PET or SPECT.

Abstract: The invention provides methods for modulating the immune response caused by CpG dinucleotide-containing compounds. The methods according to the invention enables both decreasing the immunostimulatory effect for antisense applications, as well as increasing the immunostimulatory effect for immunotherapy applications.

Abstract: The present invention provides novel compounds comprising cellular phosphoinositides and analogues tagged with stable or radioactive isotopes. The present invention also provides novel methods for the preparation of the said phosphoinositides by syntheses, and novel key intermediates of synthesis; the novel methods of synthesis are applied also for the preparation of the phosphoinositides in non-labelled form. In addition, the present invention discloses a class of novel compounds as isotope labelled key precursors of labelled phosphoinositides. These precursors are derivatives of the target phosphoinositides, labelled with stable or radioactive isotopes, wherein OH and phosphate groups are blocked with temporary protecting groups.

Abstract: The invention relates to a method of preparing a solution of a radioactive rhenium complex, by reacting at elevated temperature a radioactive perrhenate in a substantially aqueous solution with a ligand in the presence of a reductant and optionally an antioxidant under substantially anaerobic conditions, wherein said reaction is carried out at a pH from approx. 1.5 to approx. 5 and by heating the reaction components for at least 10 min. at a temperature of at least 100° C. The invention further relates to a kit for performing said method.

Abstract: The present invention provides a kit and a method for targeting of a diagnostic or therapeutic agent to a target site in a mammal having a pathological condition. The kit comprises, in separate containers, (a) a first conjugate comprising a targeting moiety and a Morpholino oligomer, wherein the targeting moiety selectively binds to a primary, target-specific binding site of the target site or to a substance produced by or associated with the target site; (b) optionally, a clearing agent; and (c) a second conjugate comprising a complementary Morpholino oligomer and a diagnostic agent or therapeutic agent. The method comprises administering (a), optionally (b), and (c) to a mammal.

Abstract: The present invention is directed to particular bisphosphonate compounds, and in particular, to bisphosphonate conjugates that are useful in the treatment of soft tissues surrounding bone and bone-related diseases, such as bone cancer and osteoporosis.

Abstract: The present invention relates to cryptate compounds useful as chelating agents. In particular, the present invention relates to functionalized derivatives of certain cryptate compounds. These functionalized derivatives are suitable for use in radiolabelling and similar applications. The present invention also relates to a method for diagnosis or therapy of a disease utilizing functionalized derivatives of cryptase compounds.

Abstract: This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the PIII centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g.

Abstract: Tripodal polyaminophosphonate chelants are disclosed, as well as chelates of the chelants with metal ions to form radiopharmaceutical and radioactive, MRI and X-ray or CT imaging compounds and compositions. Therapeutic and imaging methods of use are also disclosed.

Abstract: An object of the present invention is to provide a bisphosphonic acid derivative and said bisphosphonic acid derivative being labeled with a radioactive nuclide, which has properties of rapid accumulation to the bone and rapid urinary excretion. The present invention relates to a bisphosphonic acid derivative and said bisphosphonic acid derivative being labeled with a radioactive nuclide, which is represented by the following general formula (1), R—Y—A  (1) wherein A is a bisphosphonic acid or a salt thereof, having P—C—P bond; Y is a bonding portion such as a methylene, an amido etc.

Abstract: A formulation and method for therapeutic treatment of in mammals using certain metals or particle-emitting radionuclides complexed with tetraazamacrocyclic ligands are described.

Abstract: This invention relates to medical uses of radiopharmaceuticals. Specifically, the present invention relates to the use of radiopharmaceuticals to treat osteomyelitis. The present invention provides improved system and methods of for the direct delivery of radiopharmaceuticals to the site of osteomyelitis.

Abstract: The present invention provides a pharmaceutical compound, or pharmaceutically acceptable salt thereof, for use in medicine, wherein said compound is of formula I wherein R is a pharmaceutically active moiety; Ar is an aromatic moiety; X is a linker group; and Y is a moiety comprising two phosphonate groups. Further aspects of the invention relate to a method for palliative and curative treatment of bone disorders and cancer related disorders, such as breast cancer.

Abstract: A radiotherapeutic agent comprising a 32P or 33P radiolabeled protein selected from the group consisting of: wherein X is an targeting peptide, Y is a phosphorylation peptide, L is a flexible linker, preferably a peptide linker, and SH2 represents an SH2 domain; whereby said phosphorylation peptide is radiolabeled with 32P or 33P

Abstract: A 99mTc complex which contains the moiety Tc═NR, Tc—N═NY or Tc(—N═NY)2, and as a synthetic organic ligand which confers biological target-seeking properties on the technetium complex,

Abstract: The present invention provides novel radiopharmaceuticals useful for imaging the heart, brain, lungs, liver or kidneys, kits useful for preparing the radiopharmaceuticals, and methods of imaging the heart, brain, lungs, liver or kidneys in a patient in need of such imaging. The radiopharmaceuticals are comprised of technetium or rhenium radionuclide complexes of a ternary ligand system: one hydrazido or diazenido ligand, one aminoalcohol ligand, and one pi-acid ligand selected from phosphines, arsines, and imine nitrogen-containing heterocycles. The radiopharmaceuticals have the formula, ML1L2L3, wherein the variables are as defined herein.

Abstract: The invention concerns a radio-labeled antithrombogenic polymer and its use as part of therapeutic means to prevent excessive cell proliferation or scarring, and means which comprise the radiolabeled antithrombogenic polymer, such as emplastrum or artificial implants with a biocompatible coating.

Abstract: The present invention provides novel compounds comprising cellular phosphoinositides and analogues tagged with stable or radioactive isotopes. The present invention also provides novel methods for the preparation of the said phosphoinositides by syntheses, and novel key intermediates of synthesis; the novel methods of synthesis are applied also for the preparation of the phosphoinositides in non-labelled form. In addition, the present invention discloses a class of novel compounds as isotope labelled key precursors of labelled phosphoinositides. These precursors are derivatives of the target phosphoinositides, labelled with stable or radioactive isotopes, wherein OH and phosphate groups are blocked with temporary protecting groups.

Abstract: The invention provides cardiovascular imaging agents comprising a radionuclide in association with a nucleotide polyphosphate targeting molecule. Methods for using the cardiovascular imaging agents and kits containing the cardiovascular imaging agents or components suitable for production of the cardiovascular imaging agents are also provided.