Abstract: The present invention describes the use of radio-labeled antitumor drugs in the treatment of solid tumors by the method of administering a radio-labelled anticancer drug to a patient and imaging at least a part of the patient using Positron Emission Tomography imaging. The method is used to monitor delivery of antitumor drugs to tumors and may be used to predict the effectiveness of therapy with a particular antitumor drug or combination of antitumor drugs, to assess the effectiveness of modulators of cellular accumulation, to individualize therapy and to evaluate the effectiveness of antitumor drugs with respect to particular cancers. Particularly preferred drugs are labeled taxanes, e.g., 11C-paclitaxel and 11C-docetaxel, labeled anthracyclines, e.g., 11C-doxorubicin and 11C-epirubicin, and other radio-labeled drug, e.g. 11C-topotecan and 11C-mitoxantrone. The invention further describes antitumor drugs labeled with the radioactive label 11C and methods of preparing radio-labeled drugs.

Abstract: The present invention relates to targetable constructs which may be bound by a bi-specific antibody or antibody fragment having at least one arm that specifically binds construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the targetable constructs and bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: A stabilized dispersion of metal fine particles comprising, fine particles of metal which is obtained by reducing at least one metallic acid or salt thereof selected from the group consisting of haloauric acid, haloplatinic acid, silver nitrate and halorhodic acid by a reducing agent in the aqueous solution of (1) R-PEG-SX [R is a functional group selected from the group consisting of acetal, aldehyde, hydroxyl group, amino group, carboxyl group, active ester group, azide group, biotin group, monosaccharide, oligosaccharide, amino acid, nucleic acid, allyl group, vinyl benzyl group, methacryloyl group and acryloyl group, PEG is —(CH2CH2O)n—, X is H or pyridylthio group] or (2) R-PEG/PAMA (given structural formula A), and said fine particles load a polymer having PEG unit possessing above mentioned functional group on the surface.

Abstract: Disclosed are Drug Delivery Molecules (DDMs) which both facilitate functional imaging, as by PET or SPECT, and create a biological effect and methods of their use. These DDMs are variously designed to target specific receptors, then become internalized and then function biologically, as for purposes of cell destruction or therapy.

Abstract: The present invention provides compounds, or salts or solvates thereof, which can be used as probes for the imaging diagnosis of diseases in which tau protein accumulates, and compositions and kits comprising such compounds, or salts or solvates thereof. The present invention also provides a method for staining neurofibrillary tangles in brain samples, and a pharmaceutical composition for the treatment and/or prophylaxis of a disease in which ?-sheet structure is the cause or possible cause.

Abstract: A liposome containing a hydrophobic iodine compound such as a 1,3,5-triiodobenzene derivative having at least one substituent containing 18 or more carbon atoms as a membrane component, and an X-ray contrast medium containing the liposome for use in radiography of a vascular disease and the like.

Abstract: A fibrin/fibrinogen binding conjugate for forming a depot for the sustained release of a pharmaceutically active substance from a fibrin clot. The conjugate comprises a fibrin/fibrinogen binding moiety bound to a pharmaceutically active substance either directly or via an intervening substance capturing moiety such as an antibody. The conjugate can also be a recombinant fusion protein comprising a fibrin/fibrinogen binding moiety such as VEGF165 C-terminal domain fused to a wound-healing substance such as leptin.

Abstract: This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides.

Abstract: A method for treating arteriosclerotic lesions is provided wherein the method is characterized by administering a chemical compound to the patient, the compound being a porphyrin complexed with a radioactive metal. Cells which exhibit an affinity for the porphyrin element indicate sites of plaque buildup. The radioactive metal within the compound is cytotoxic to cells in and surrounding the plaque and may allow tomographic scanning of the plaque as well. The complexed compound can be introduced to the patient a desired number of times to provide the necessary radiation treatment and ongoing monitoring of plaque removal.

Abstract: The invention provides imaging agents comprising a label in association with a plaque specific targeting molecule. Methods for using the imaging agents to diagnose or monitor plaque formation and growth and kits containing the cardiovascular agents or components suitable for production of the imaging agents are also provided.

Abstract: Iodinated and/or brominated derivatives of aromatic dihydroxy monomers are prepared and polymerized to form radio-opaque polymers. The monomers may also be copolymerized with other dihydroxy monomers. The iodinated and brominated aromatic dihydroxy monomers can be employed as radio-opacifying, biocompatible non-toxic additives for other polymeric biomaterials. Radio-opaque medical implants and drug delivery devices for implantation prepared from the polymers of the present invention are also disclosed.

Abstract: A method and compositions are described for labeling a targeting agent with Ga-68, in which eluate from an acid-eluted Ge-68/Ga-68 generator is combined with a macrocycle-containing targetable agent. The labeling method and compositions disclosed ensure that a simple elution of gallium-68, taken directly from a generator, can be used without further manipulation to quantitatively label a macrocycle-containing targetable agent. The Ga-68 labeled targeting agent so produced is useful with specific targeting agents, and is most especially useful in a pretargeting method for positron emission tomographic detection.

Abstract: Low density microspheres, methods for preparing same, and use of same as contrast agents are described. The microspheres have a void having a volume that comprises at least about 75% of the total volume of the microspheres, and which contains a gas or the vapor of a volatile liquid selected from the group consisting of aliphatic hydrocarbons, chlorofluorocarbons, tetraalkyl silanes and perfluorocarbons.

Abstract: Detectably labeled macrophage scavenger receptor antagonists useful for the diagnosis and monitoring of various cardiovascular diseases including but not limited to atherosclerosis, vulnerable plaque, coronary artery disease, renal disease, thrombosis, transient ischemia due to clotting, stroke, myocardial infarction, organ transplant, organ failure and hypercholesterolemia.

Abstract: Disclosed are novel compositions for embolizing blood vessels which are particularly suited for treating vascular lesions via catheter deliver.

Abstract: Thiol-containing peptides can be radiolabeled with fluorine-18 (F-18) by reacting a peptide comprising a free thiol group with an F-18-bound labelling reagent which also has a group that is reactive with thiols. The resulting F-18-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the F-18-labeled peptide or a low molecular weight hapten conjugated to the F-18-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.

Abstract: The present application is directed to the use of X-ray contrast media that act as universal antigens that are labeled herein as “pseudoantigens.” X-ray contrast media have the potential to exist in an aggregated state that is greater in increased concentrations. In this aggregated state, contrast media assume the role of multivalent antigens and can successfully compete with any other antigens involved in antibody-antigen reactions that lead to anaphylaxis. In this competition, the large quantity of contrast media serves to inhibit the adverse effects of antibody-antigen reactions without the contrast media itself creating antibodies or creating toxicity problems.

Abstract: The present invention provides a conjugate wherein GP (glycoprotein) Ib and a lipid are bonded via polyalkylene oxide. The present invention also provides a complex (GPIb lipid complex) containing this conjugate and a free lipid. The GPIb lipid complex is expected to have a potential for practical application in a wide range, as a platelet substitute, a pharmaceutical agent for the prophylaxis or treatment of angiopathy, vascular damage and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent thereof. Moreover, the GPIb lipid complex of the present invention is also superior in retention property in blood, which enables continuous expression of a pharmacological action.

Abstract: The invention relates to new, monomeric, perfluoroalkyl-substituted metal complexes, processes for their production, and their use in diagnosis and therapy. The compounds according to the invention are suitable especially as in vivo contrast media in nuclear spin tomography (MRT). They can preferably be used as blood-pool agents and as lymphographic agents.

Abstract: A chimeric antibody with human constant region and murine variable region, having specificity to a 35 kDA polypeptide (Bp35(CD20)) expressed on the surface of human B cells, methods of production, and uses.

Abstract: This invention is directed to the use of radiopharmaceuticals in diagnosing Alzheimer's disease. In particular the radiopharmaceuticals of the invention are able to pass through the blood-brain barrier and bind to the CCR1 receptor present in brain tissue of patients having Alzheimer's disease.

Abstract: Oily paclitaxel composition and formulation for chemoembolization and preparation method thereof solubilizing paclitaxel in an oily contrast medium. The composition of the present invention solubilizes paclitaxel and has an advantage of delivering anticancer drug to the target cells by chemoembolization since it is possible to visualize the blood vessel during the chemoembolization process. The present invention also relates to oily paclitaxel composition and formulation additionally comprising chemicals that prevent paclitaxel precipitation for prolonged preservation and the preparation method thereof. Since the composition of the present invention solubilize paclitaxel effectively and can be visualized during chemoembolization, it can be used for TACE to treat hepatoma and other solid tumors.

Abstract: Disclosed are compositions, methods, and kits of parts suitable for use in embolizing blood vessels. In particular, disclosed are embolizing compositions, methods, and kits comprising a biocompatible polymer, a biocompatible solvent, and a high concentration of contrast agent.

Abstract: Metal nanoparticles are described that are useful for enhancing the contrast of x-rays or other radiation sources. A method is disclosed whereby the agents are administered intravenously or intra-arterially to detect coronary senses and other vascular features. It is also disclosed how directing moieties attached to the metal particles are used to detect specific targets.

Abstract: A method wherein a radiolabelled compound is localized at a thrombus. Two-dimensional images, representing a physical property associated with the radiolabelled thrombus, are acquired and assembled into a three-dimensional matrix of data. The three-dimensional matrix of data is then scanned along an array of parallel lines to determine a maximum value along each line. The maximum value along each line is then assigned to a pixel in a two-dimensional array, where the relative position of the pixel in the two-dimensional array corresponds to the relative position of the line in the array of parallel lines.

Abstract: Liposomes of a specific bilayer composition containing an entrapped modifying compound are claimed. The liposomes of the invention are suitable for the internalisation of a variety of materials, even following long-term storage. Suitable materials of the invention include radiometals, parmagnetic compounds, radioopaque compounds and prodrugs. Upon internalisation, the material reacts chemically with the entrapped modifying compound such that said material remains internalised within the liposomes of the invention. Also claimed in the present invention are the liposomes containing internalised material and kits for their preparation. Furthermore, the use of said liposomes containing internalised material for the imaging infection, inflammation or tumour in a human is claimed.

Abstract: Systems and methods for radiographic imaging of tissue using a radio-opaque imaging agent that in one embodiment accumulates intracellularly in tissue in proportion to its functional, or physiological, activity. In one embodiment, the imaging agent is a cell membrane-permeable, radio-opaque, high affinity ligand for an intracellular target. The imaging agent is administered to a patient, and after an accumulation interval, radiographic images are acquired. The imaging agent preferentially accumulates in certain types of tissue and increases its radio-opacity. The tissue being examined is transilluminated by X-ray beams with preselected different mean energy spectra, and a separate radiographic image is acquired during transillumination by each beam. An image processing system may perform a weighted combination of the acquired images to produce a single displayed image. The system and method thus provides a functional image displayed with the anatomical detail and spatial resolution of a radiographic image.

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: The present invention is directed to polymeric prodrug transport forms and methods of making and using the same. In one preferred aspect, the prodrugs are of the formula: wherein G is a polymeric residue; Z is one of: and B is a residue of a biologically active amine-containing moiety or a hydroxyl-containing moiety.

Abstract: Disclosed are compositions for site specific delivery in the body including diseased vasculature (e.g., aneurysmal sacs, arteriovenous malformations, etc.), body lumens such as the vas deferens and fallopian tubes, cavities created in vivo for the purpose of tissue bulking, and the like. Also disclosed are methods employing such compositions as well as kits comprising such compositions.

Abstract: Low density microspheres, methods for preparing same, and use of same as contrast agents are described. The microspheres have a void having a volume that comprises at least about 75% of the total volume of the microspheres, and which contains a gas or the vapor of a volatile liquid selected from the group consisting of aliphatic hydrocarbons, chlorofluorocarbons, tetraalkyl silanes and perfluorocarbons.

Abstract: The modulation or elimination of an allergic condition according to the invention can be achieved by injecting small amounts of allergen directly into a lymph node, which greatly reduces the potential for side effects.

Abstract: The present invention concerns a method for selectively targeting a medicinally-useful agent into cells in which a phospholipid scramblase (PLS) transport system is activated. The method comprises administering the agent, being a PLS-dependent transported compound (PDTC) to the cells, thereby causing selective transport of the agent into the cells. Examples of the cells are apoptotic cells, activated cells and injured cells. Also disclosed are pharmaceutical compositions for use by the method.

Abstract: Disclosed are compositions suitable for use in embolizing blood vessels which compositions comprise a polymer, a biocompatible solvent and a contrast agent. The polymer is selected from the group consisting of polyacrylonitrile, polyurethane, polyvinylacetate, cellulose acetate butyrate, nitrocellulose and copolymers of urethane/carbonate and copolymers of styrene/maleic acid.

Abstract: A nitroimidazole derivative represented by the following formula (1): [wherein R1 represents a hydrogen atom or a C1-C4 alkanoyl group; and X represents a fluorine atom or an isotope thereof], and a diagnostic imaging agent containing the derivative as an active ingredient. The derivative enables imaging of the ischemic sites of a circulatory organ or imaging of cancer cells, and thus the derivative can provide information about the position and the amount of the ischemic sites or the cancer cells. Therefore, the derivative contributes to selection of appropriate treatment of ischemia or cancer.

Abstract: Improved methods for detecting lesions in dense breast tissue are disclosed. The methods of the invention generally feature administration to a subject of an LHRH antagonist in an amount and for a period of time sufficient to reduce the density of breast tissue prior to generating an image of the breast tissue, for example by mammography, to detect a lesion in the breast tissue. Packaged formulations for reducing breast density in a subject prior to generating an image of the subject's breast tissue, comprising an LHRH antagonist packaged with instructions for using the LHRH antagonist to reduce breast density in a subject prior to imaging the breast tissue, are also disclosed.

Abstract: The present invention relates to microspheres useful for embolization which comprises polyvinylalcohol. The present invention also relates to an injectable suspension suitable for embolization which comprises the polyvinylalcohol microspheres and a suitable liquid carrier. The present invention further relates to a method for prophylactic or therapeutic embolization which comprises administering to a mammal an injectable suspension containing the polyvinylalcohol microspheres and a suitable liquid carrier. Finally, the present invention relates to a process for producing the polyvinylalcohol microspheres.

Abstract: An orally ingestible baked radiopaque product comprising (a) fat, (b) sweetener, (c) moisturizing agent, (d) x-ray contrast agent, (e) flour and (f) optionally flavoring agent useful for evaluating swallowing food having a dry rood texture. The x-ray contrast agent is interspersed throughout the product by mixing it into the product prior to baking it. The product is used in the detection of dysphagia. A method and dough useful for preparing the product.

Abstract: The present invention provides basic ionic contrast agents that have anticoagulant activity. The contrast media incorporate a lysine or arginine group or derivative, and have a free amino or guanidino group. Methods of using the contrast media are also disclosed.

Abstract: A stool marker formulation for oral administration and suitable for use in CT Colography including a material adapted to provide marked stool which has a modified response to radiation relative to unmarked stool. Radiologically scanning the colon of a patient treated to produce marked stool produces data which can be manipulated to provide a representation of the colon including where present, a polyp. The active ingredient is preferably barium sulfate which has been destabilised to reduce its resistance to flocculation.

Abstract: Systems and methods for radiographic imaging of tissue using a radio-opaque imaging agent that in one embodiment accumulates intracellularly in tissue in proportion to its functional, or physiological, activity. In one embodiment, the imaging agent is a cell membrane-permeable, radio-opaque, high affinity ligand for an intracellular target. The imaging agent is administered to a patient, and after an accumulation interval, radiographic images are acquired. The imaging agent preferentially accumulates in certain types of tissue and increases its radio-opacity. The tissue being examined is transilluminated by X-ray beams with preselected different mean energy spectra, and a separate radiographic image is acquired during transillumination by each beam. An image processing system may perform a weighted combination of the acquired images to produce a single displayed image. The system and method thus provides a functional image displayed with the anatomical detail and spatial resolution of a radiographic image.

Abstract: A method of contrast agent-enhanced imaging involving induction of vasomodification, e.g. by physical or pharmacological means, in which pre- and post-vasomodification images in respect of free-flowing contrast or tracer agent in a substantially steady state distribution are recorded as part of a single imaging sequence and are compared to identify any local variations resulting from changes in vascular volume caused by the vasomodification. Imaging techniques which may be employed include ultrasound imaging, magnetic resonance imaging, X-ray imaging and nuclear tracer techniques such as scintigraphy.

Abstract: A delivery system and method for targeting a contrast agent to tissues and organs for improved diagnosis of tumors and for prognosis and follow-up of cancer therapy by X-ray imaging. The delivery system includes a conjugate or complex of a macromolecular carrier and a contrast agent selected from the group consisting of: (a) a compound having a heavy element with an atomic number in the range of 75 to 92, and (b) a compound having an element with a property of an abrupt change in its X-ray attenuation coefficient within the energy range used for radiography, said macromolecular carrier of said conjugate or complex being optionally linked to a specific tissue marker molecule.

Abstract: Sequential injections of contrast agents are employed for assessing angiogenic activity. At least one of the injections is of a polymeric contrast agent which binds to angiogenic microvasculature.

Abstract: A non-implantable CT and MRI marker has a first component formed of at least one of a silicone resin and a fluorcarbon resin and a second component comprised of at least one of an elastomer and an organogel contained in the first component.

Abstract: The present invention describes novel compounds of the formula: (Q)d-Ln-Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety.

Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

Abstract: Perfluoroalkyl-containing complexes with polar radicals of general formula I (K)1-G-(Z-Rf)m(R)p  (I) in which R means the polar radical, Rf means a perfluorinated carbon chain, K is a metal complex, and Z represents a linker group, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

Abstract: An contrast agent for therapeutic or diagnostic treatment comprises a fullerene scaffold and an iodinated moiety bonded to the scaffold. The agent may further comprise a water solubilizing moiety bonded to the scaffold, which may be a serinol malonodiamide, hydroxyl, and 1,3-diol. The fullerene scaffold may comprise an empty fullerene or an endohedral fullerene. A method for making the agent includes a) synthesizing iodinating moieties, b) protecting serinols, forming protected serinols, c) attaching the protected serinols to the iodinated moieties, forming iodinated serinols, d) attaching the iodinated serinols to the fullerene scaffold, and, optionally, d) de-protecting the serinols. Also disclosed are a method for providing diagnostic treatment to a patient comprising administering to said patient a radiopaque effective amount of a contrast agent comprising a fullerene scaffold and an iodinated moiety, a method of making a blood pool agent.

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 position 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.