Abstract: The method for diagnosing lactose intolerance in patients by the oral administration of defined amounts of lactose, followed by assaying metabolites of lactose, is performed in a way where the lactose administered contains 99% 13C-labeled lactose, preferably from 5 to 30 mg, and after the administration of the lactose, the content of 13C-labeled lactose is determined in a serum sample taken at a defined time after the administration. A diagnostic kit for performing the method consists of a capsule with from 5 to 30 mg of 99% 13C-labeled lactose, a patient instruction manual, a blood sampling device, sample containers for collecting the blood sample, and optionally a spatula and sample container for a stool specimen.

Abstract: An 18F isotope-labeled FDG radiopharmaceutical is stabilized against degradation in radiochemical purity due to radiolysis using selected amounts of ethyl alcohol that depend on the activity concentration of the 18F with due regard to limits set by various pharmacopoeia standards. Any of the well-know production methods for the FDG may be used and the ethyl alcohol added at several stages, preferably as part of the standard hydrolysis step. This particular radiopharmaceutical is used extensively in diagnostic imaging with a Positron Emission Tomography technique.

Abstract: Radiopharmaceutical compositions which are stabilized by addition of a mixture of a hydrophilic thioether and a hydrophilic 6-hydroxy-chroman derivative.

Abstract: Methods are provided for cancer and pre-cancer detection by increased uptake of fluorophore glucose or deoxyglucose conjugates in cancerous and pre-cancerous cells relative to normal cells.

Abstract: A delivery vehicle is described that is capable of being specifically bound to and taken into targeted cells, delivering numerous physiological agents, particularly paramagnetic ions for magnetic resonance imaging (MRI) of the cells. The delivery vehicle comprises a polymeric molecule having a net positive charge complexed with another polymeric molecule having a net negative charge. Cell targeting moieties and physiological agents, including contrast agents and therapeutic agents, are attached to one or both of the polymeric molecules. In one embodiment, the polymeric molecule having a net negative charge is a nucleic acid. Thus, the delivery vehicles can be used in clinical protocols in which nucleic acids for gene therapy and agents for MRI contrast are co-transported to specific cells allowing medical imaging monitoring of nucleic acid delivery.

Abstract: This invention discloses a method for preparing a complex comprised of a VEGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a VEGF Nucleic Acid Ligand by SELEX methodology and associating the VEGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more VEGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a VEGF Nucleic Acid Ligand or Complex and methods for making the same.

Abstract: Methods for imaging and targeting tumor vasculature are provided. Specifically, the methods for imaging and targeting tumor vasculature relate to using ephrin-B2 to image developing tumor vasculature and to target therapeutic agents to developing tumor vasculature. Kits for imaging and targeting tumor vasculature are also provided. Also provided for are methods of delivering agents to vasculature.

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

Abstract: This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.

Abstract: Methods and compositions for treating or ameliorating diseases and other conditions, such as infectious diseases, autoimmune diseases and allergies are provided. The methods employ cyclic AGPs for selectively stimulating immune responses in animals and plants.

Abstract: The present invention provides a 13C-labeled oligosaccharide or polysaccharide or a salt thereof excluding U-13C-maltose, 13C-starch, 1-13C-maltotetraose and 1-13C-amylose; a derivative of the 13C-labeled oligosaccharide or polysaccharide or salt thereof; a 13C-labeled inclusion complex or a salt thereof, which comprises a cyclodextrin or a modified derivative thereof as a host molecule; a 13C- or 14C-labeled fluorescein ester compound or a salt thereof; and a diagnostic agents for pancreatic exocrine function comprising these compounds 13C- or 14C-labeled.

Abstract: Radiopharmaceutical compositions which are stabilized by addition of a hydrophilic thioether.

Abstract: A “reverse isotope dilution assay” herein, wherein a pathway that produces a given metabolite is assayed by diluting a labelled metabolite produced by a second constitutive pathway. In one aspect, the invention relates to a method for monitoring lactose maldigestion or lactose intolerance in humans. Specifically, the method requires administering a reverse tracer of labeled glucose and unlabeled lactose to an individual and assessing labeled carbon dioxide in breath or blood. If the lactose is digested, the labeled CO2 produced by the labeled glucose is diluted by the metabolism of the lactose.

Abstract: Radiopharmaceutical compositions which are stabilized by addition of a hydrophilic 6-hydroxy-chroman derivative.

Abstract: The invention provides cyclodextrin derivatives that may be used to transport hydrophobic molecules for pharmaceutical or cosmetic applications, by forming organised systems in an aqueous medium, alone or with phospholipids. The cyclodextrin derivatives of the present invention have the formula: in which, R1 represents a steroid, R2 represents an alkyl or aryl group, substituted if applicable, R3 represents H or R2, all the R4 represent OR2, or one of the R4 represents —NHCO(CH2)mCONHR1, m is an integer ranging from 1 to 8, and n is equal to 5, 6 or 7.

Abstract: The invention provides detectably labeled cobalamin derivatives which are useful for medical treatment and diagnosis.

Abstract: 2′-Deoxy-2′-[18F]-labeled and 3′-deoxy-3′-[18F]-labeled purine nucleoside analogs such as [18F]-FAA and [18F]-FXA have been found to have desirable properties for use as imaging agents. The analogs are particularly useful for in vivo imaging of biological material including organ tissues (e.g., heart, liver, brain and kidneys) and tumors. Methods for the preparation of the [18F]-FAA and [18F]-FXA are also provided.

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 present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively as a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis.

Abstract: The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively as a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis.

Abstract: Provided herein are methods for determining the metabolism of one or more sugars and/or fatty acids, and applications thereof. Such applications include determining the rate of glycogen synthesis and glycolysis, which are believed to be early markers for predicting elevated risk of diabetes and cardiovascular disease. Other applications include methods for screening drugs that effect sugar and/or fatty acid metabolism. The methods are useful for at least partially characterizing drugs for desirable or undesirable (toxic) characteristics. Drugs that are at least partially characterized using the methods of the invention can then be further developed in pre-clinical testing and clinical trials. Such drugs may be found to be useful in treating obesity, diabetes, cardiovascular disease, and other disorders of metabolism.

Abstract: Novel azo compounds and their bioconjugates for phototherapy and/or photodiagnosis of tumors and other lesions. The azo derivatives of the present invention are designed to absorb at the low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photoexcitation of the azo compound, with the tissue of interest.

Abstract: The present invention relates to a radiolabeled DNA carrier, a method of preparation thereof and the therapeutic uses of this substance to prevent uncontrolled cellular proliferation. The invention also relates to devices incorporating the above radiolabeled DNA carrier (such as an oligonucleotide) for the therapeutic treatment of uncontrolled cellular proliferation. More specifically, the present invention is concerned with the prevention of restenosis by intravascular delivery of radiolabeled DNA carrier at a dilatation site of an artery. This invention is also directed to a method of treatment of vascular proliferative diseases and/or other proliferative disorders such as cancer and related metastasis.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: Materials and methods for studying and modulating the interaction of carbohydrate-containing moieties with other species are described, in particular, small particles, e.g. clusters of metal or semiconductor atoms, which can be employed as a substrate for immobilising a plurality of ligands comprising carbohydrate groups. These “nanoparticles” can then be used to study carbohydrate mediated interactions, e.g. with other carbohydrates or proteins, and as therapeutics and diagnostic reagents.

Abstract: A halogen-labeled gene therapy construct that includes halogen-labeled nucleic acids, methods for preparing a halogenated gene therapy construct, and methods for in vivo imaging of the same. Also provided are methods for non-invasive drug detection in a subject using a labeled antibody that recognizes a heterologous antigen conjugated to, encoded by, or otherwise associated with the drug.

Abstract: The invention provides compositions and methods for the production of achromosomal and anucleate cells useful for applications such as diagnositic and therapeutic uses, as well as research tools and agents for drug discovery.

Abstract: Perfluoroalkyl-containing complexes with sugar radicals of general formula I in which R represents a monosaccharide or oligosaccharide radical that is bonded via the 1-OH position or 1-SH position, Rf means a perfluorinated carbon chain, K is a metal complex, and Y and Z represent linker groups, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

Abstract: The present invention provides methods and compositions for imaging cell death in vivo, as well as methods and compositions for tumor radiotherapy.

Abstract: Processes for the preparation, prepared solutions, and the use of radium-223 for the treatment of calcified tumors, bone tumors, treatment of bones, bone surfaces and soft tissues is described.

Abstract: Novel TNF reccptor polypeptides are disclosed, along with polynucleotides encoding the polypeptides and uses thereof.

Abstract: This invention provides imaging reagents for the detection of a gene or gene expression product (e.g. mRNA) in a brain cell in vivo. Preferred reagents comprise a detectable label attached to a first nucleic acid that specifically hybridizes to the gene or to a nucleic acid transcribed from the gene. The first nucleic acid is linked to a targeting ligand that is capable of binding a receptor on a cell comprising the blood brain barrier and crossing said blood brain barrier.

Abstract: A compound useful for in vivo imaging of organs and tumors is provided of formula: wherein is a cobalamin, is derived from a corrin carboxylic acid group of said cobalamin, Y is a linking group and X is a chelating group, optionally comprising a detectable radionuclide or a paramagnetic metal ion, and n is 1-3.

Abstract: The present invention provides methods of treating proliferative disorders in vivo by the direct administration of tritium to target cell nuclei. Tritium is administered to target cell nuclei by a tritiated nuclear targeting agent, which is directed to the target cell nucleus where it associates with the cell's DNA. The close association of the tritiated nuclear targeting agent with the target cell DNA allows the low-energy beta particle emitted by the tritium to damage to the target cell DNA and kill the cell. Tritiated nuclear targeting agents can also be delivered to the target cells by structures such as liposomes, micelles and microcapsules.

Abstract: This invention discloses a method for preparing a complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a PDGF Nucleic Acid Ligand by SELEX methodology and associating the PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more PDGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a PDGF Nucleic Acid Ligand or Complex and methods for making the same.

Abstract: A method of evaluating the effects of administering an external stimuli or treatment such as a psychoactive compound, a drug, or an environmental influence like temperature, noise, vibration, light and similar sensory-perceived influences, on a subject's brain using imaging techniques with positron emission tomography (PET). The method measures cerebral metabolism before and after administering the external stimuli or treatment, and employs a behavioral clamp to control behavioral influences on the subject's brain after administration of the external stimuli or treatment.

Abstract: A meat-free, algae-free, standardized, test meal kit used in the measurement of delayed gastric emptying is provided. The kit contains at least a standardized test meal dry mix and tracer. A method of using the kit is also provided.

Abstract: In a method for characterizing the angiogenesis status of a tumor in a living subject, timed magnetic resonance images of the subject into whom a reptating polymer contrast agent containing chelating diethylentriaminepentacetic acid dosed with gadolinum has been introduced are obtained. At least two images taken at different times are compared in order to determine the percentage image enhancement in a tumor region of interest. A contrast agent including a reptating polymer containing technetium-99 is used with a nuclear medicine version of this technique.

Abstract: Iodinated neuroprobes for mapping monoamine reuptake sites in the brain, and particularly iodinated neuroprobes that can also serve as radiotracers for use in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging of such reuptake sites, are disclosed. Precursors of radiolabeled iodinated neuroprobes, both with and without a radiotracer atom, and kits for preparing the radiolabeled iodinated neuroprobes are also disclosed.

Abstract: This invention relates to novel highly functionalized phosphine ligands as ancillary ligands in radiopharmaceuticals. Also, this invention provides radiopharmaceuticals comprised of highly functionalized phosphine ligated 99mTc labeled HYNIC-conjugated biomolecules that selectively localize at sites of disease and thus allow an image to be obtained of the loci using gamma scintigraphy. The invention also provides methods of use of the radiopharmaceuticals as imaging agents for the diagnosis of cardiovascular disorders such as thromboembolic disease or atherosclerosis, infectious disease and cancer.

Abstract: The invention provides targeted constructs comprising a targeting moiety, a nucleic acid, and a payload. The payload can be a detectable label or a therapeutic agent. The nucleic acid can be an antisense molecule that is complementary to RNA present in a target cell. The targeted constructs can be used to introduce the payload into a target cell in vivo or in vitro. Accordingly, the invention can be used for diagnostic purposes and for therapeutic purposes.

Abstract: This invention provides compounds containing a 2-deoxy-2-amino-&bgr;-D-glucopyranose (glucosamine) glycosidically linked to an cyclic aminoalkyl (aglycon) group. The invention further provides methods for inducing an immune response using the compounds of the present invention in the presence or absence of an antigen. In addition, methods for treating disease with the compounds of the present invention with or without an antigen are also provided in this invention.

Abstract: Large cobalt and nickel complexes that may be linked to antibodies and other molecules are described. These may be useful in applications benefiting from their magnetic properties.

Abstract: Fluorine-18, fluorine-18-incorporating radiopharmaceuticals (FRPs), and other positron-emitting isotopes and radiopharmaceuticals have been used for diagnostic purposes in positron emission tomography (PET). This invention describes the therapeutic use of positron-emitting radiopharmaceuticals such as FRPs primarily, but not exclusively, for the treatment of cancer and cancer-related illnesses. The radiopharmaceuticals are administered in dosages significantly higher than those used for diagnostic imaging.

Abstract: The present invention discloses a method for the enzyme-mediated, site-specific, in-vivo precipitation of a water soluble molecule in an animal. The enzyme is either unique to tumor cells, or is produced within a specific site (e.g., tumor) at concentrations that are higher than that in normal tissues. Alternatively, the enzyme is conjugated to a targeting moiety such as an antibody or a receptor-binding molecule.

Abstract: Described are methods for stabilizing radionuclide-containing compositions against degradation caused by free radicals generated from the radionuclide. Iodide ions stabilize the radionuclide-containing compositions by acting as scavengers to generated free radicals, thus, preventing or lessening degradation therefrom. Among the preferred radionuclide-containing compositions to be stabilized are complexes of a complexing agent with a radionuclide complexed therewith, such as a diagnostic agent having a specific binding peptide linked to a metal ion-complexing moiety which is complexed with a radionuclide, such as technetium-99m (Tc-99m).

Abstract: The invention relates to a polysaccharide-peptide conjugate wherein the polysaccharide is advantageously immunogenic, which comprises a polysaccharide chain composed of repeat units and a plurality of peptide moieties, each moiety containing a cysteine residue and being covalently attached at random along the polysaccharide chain, through an indirect bond being achieved through either a linker or a spacer-linker moiety provided that the spacer entity of the spacer-linker moiety is linked to the amino, hydroxyl or carboxyl group of the polysaccharide. To this end a useful linker may be, e.g., N-(&ggr;-maleimidobutyrloxy)succinimide ester. Such a conjugate may typically exhibit a “Rake” configuration. Conjugation processes are also disclosed. Conjugates of the invention are in particular useful in the vaccinal field to elicit a protective long term immune response against a pathogenic microorganism from which the Immunogenic polysaccharide is derived.

Abstract: Methods are described for the isolation of nucleic acid ligands to integrins using the SELEX process. SELEX is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The nucleic acid ligands of the present invention are useful as therapeutic and diagnostic agents.

Abstract: In vivo imaging of disease associated tissues, including tumors and other malignant growths, infection and inflammation, is used in the discovery, screening and development of therapeutic and/or diagnostic molecular targets for intervention in the treatment of the diseases involved. In vivo imaging is used to detect spatial and temporal variations in the imaging features of disease associated tissues. The physical regions of the tissue that correlate with imaging features are then assessed for patterns of gene expression. The corresponding genes or gene products that are upregulated in the regions of interest are useful as therapeutic and imaging targets, with enhanced spatial and/or temporal specificity.

Abstract: Methods for imaging and targeting tumor vasculature are provided. Specifically, the methods for imaging and targeting tumor vasculature relate to using ephrin-B2 to image developing tumor vasculature and to target therapeutic agents to developing tumor vasculature. Kits for imaging and targeting tumor vasculature are also provided. Also provided for are methods of delivering agents to vasculature.