WO2012136813A2 - Agents pour un diagnostic par radar médical - Google Patents

Agents pour un diagnostic par radar médical Download PDF

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Publication number
WO2012136813A2
WO2012136813A2 PCT/EP2012/056363 EP2012056363W WO2012136813A2 WO 2012136813 A2 WO2012136813 A2 WO 2012136813A2 EP 2012056363 W EP2012056363 W EP 2012056363W WO 2012136813 A2 WO2012136813 A2 WO 2012136813A2
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Prior art keywords
radar
contrast agent
sample
marker
human
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WO2012136813A9 (fr
WO2012136813A3 (fr
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Jo Klaveness
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Universitetet i Oslo
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Universitetet i Oslo
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0438—Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/0507—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves using microwaves or terahertz waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0404—X-ray contrast preparations containing barium sulfate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
    • A61K49/105—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA the metal complex being Gd-DTPA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
    • A61K49/1863—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasonic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasonic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

Definitions

  • This invention relates to in vivo the use of agents or markers for medical diagnosis based on radar technology.
  • One preferred aspect of the present invention relates to agents as contrast agents in medical imaging based on radar radiation.
  • Radar Radio detection and ranging
  • Radar systems are able to detect size, form, altitude, direction and speed of both fixed objects and moving objects.
  • Typical moving objects can be cars and other vehicles, aircrafts and space shuttles.
  • Use of radars today include both military use like air-defence systems and civil use like for example air traffic control , weather prognosis, geological radar mapping and various systems traffic monitoring systems.
  • Most radar systems monitor objects in a far distance from the radar electromagnetic source and radar monitoring system.
  • radar-based anti-collision systems for cars are able to monitor objects close to the cars.
  • US5,030,956 (Murphy) describes a radar tomography method and apparatus that generates a plurality of radar pulses in a transmitter and project them with an antenna toward a patient. Radar pulses reflected from the patient are picked up by the antenna and conducted to the receiver.
  • the described system in US5,030,956 is also able to produce three-dimensional information.
  • US2004/0249257 discloses an ultra-wide band radar known as micropower impulse radar that is combined with advanced signal processing techniques to provide a new type of medical imaging technology including frequency spectrum analysis and modern statistical filtering techniques to search for, acquire, track, and interrogate physiological data.
  • US2004/0019282 describes hybrid lidar- radar system for medical diagnostics. The radar system can be used for detecting tumors within tisues by detecting reflected signals from tissue and discriminating the information related to the tumor from the undesirable backscattering of light created by the tissue itself.
  • US2010/0234720 (Tupin) describes a system and method for extracting physiological data using ultra-wideband radar and improved signal processing techniques.
  • US2010/0292559 (Hannemann) describes a radar- equiped patient bed for a medical imaging apparatus and operating methods thereof.
  • US2009/0192384 (Fontius) describes a medical unit which comprises a three dimensional radar array for detection of positional or movement data of objects in an examination space and a processing unit for the evaluation of the detected data, with the processing unit being connected to the medical unit and the three dimensional radar array, and with the evaluated data being used to control the medical unit or for post-processing data acquired by the medical diagnostic or therapeutic unit.
  • WO2010/1241 17 (Lifewave) describes fetal and/or maternal monitoring devices, systems and methods using UWB medical radar.
  • These devices and systems may include a UWB sensor providing high-resolution and reliable simultaneous monitoring of multiple indicators of fetal and/or maternal health, such as fetal heart rate, fetal heart rate variability, fetal respiration, fetal gross body movement and other parameters during pregnancy.
  • fetal heart rate fetal heart rate variability
  • fetal respiration fetal gross body movement and other parameters during pregnancy.
  • Future use of radar medical imaging is also described by Yngve Vogt: Non-dangerous radar might replace X-ray in Appolon (University of Oslo), 2/2011 pages 36-37.
  • radar technology might be used for diagnosis of disease based on mapping of diseases tissue and by monitoring the signal reflected from the human body.
  • This signal has tended to be used in medical imaging to study natural events in which organ impedance changes occur (e.g. breathing, eating, blood flow, heart beating etc) with imaging optionally being assisted by artificially increasing the volume or fluid content of the organ under study, e.g. by administration of a meal, by increasing total blood volume, etc.
  • diagnostic imaging modalities such as X-ray, MRI, ultrasound and scintigraphy however, there has as yet been no suggestion that Ell might benefit from the use of contrast media, and in particular the use of parenterally administered contrast media, to improve organ or tissue contrast.
  • One preferred aspect of the present invention relates to agents as contrast agents in medical imaging based on radar radiation.
  • agents materials which on administration will serve to enhance the diagnostic information typically by enhancing the contrast in the resulting images by modifying the reflection of the electromagnetic radiation from the tissue in those tissues, organs or ducts into which they distribute. Where such markers and contrast agents serve to modify the local reflection of tissue they will function as modifiers of the radiation reflection as a function of the concentration of markers or negative contrast agents in the tissue, organs or ducts where they are present.
  • agent, marker and contrast agent as used herein are synonymous and may be used interchangeably.
  • Such markers and contrast media may be administered enterally or, particularly preferably, parenterally.
  • Preferred parenteral administration route is intravascular administration, more preferably intravenous administration.
  • the invention relates to the use of agents or markers for medical diagnosis based on radar technology.
  • agents or markers for medical diagnosis based on radar technology One preferred aspect of the present invention relates to agents as contrast agents in medical imaging based on radar radiation.
  • the present invention also relates to a method of diagnosis of (or imaging) a sample (e.g. a human or non-human animal subject) comprising a radar marker or radar contrast agent, said method comprising:
  • the marker or contrast agent interacts with radar radiation to a different extent than the medium of the sample in which it is located, such that the marker or contrast agent is detectable within the sample and capable of being rendered into an image showing its location within the sample.
  • One method of measuring the impact that a marker or contrast agent has on the radar radiation signal is by determining the Fresnel reflection coefficient of the marker or agent in a particular medium.
  • a high Fresnel reflection coefficient is indicative of having high contrast in that medium.
  • the imaging method preferably comprises the step of administering the radar marker or radar contrast agent to said sample (or subject). ln the imaging method, the radar marker or radar contrast agent is optionally dissolved or dispersed in a physiologically tolerable liquid carrier medium.
  • the present invention therefore relates to a method of diagnosis of (or imaging) a human or animal subject which method comprises:
  • a radar marker or a radar contrast agent optionally dissolved or dispersed in a physiologically tolerable liquid carrier medium, and
  • said marker or contrast agent being capable on dissolution or dispersion in water of yielding a fluid having an impact on the radar radiation signal in the subject.
  • the step of generating a radar based signal or image of at least part of said sample (or subject) preferably comprises
  • the invention relates to a method of producing an image of a sample containing a radar marker or radar contrast agent, said method comprising
  • the radar radiation is preferably emitted from a first antenna (e.g. in step a.), and detected at a second antenna (e.g. in step b.).
  • an array of antennas is used, such that the signal emitted from each antenna is detected by the remaining antennas in the array.
  • the step of generating a radar based signal or image of at least part of said sample (or subject) preferably comprises: i. subjecting the sample (or subject) to radar radiation emitted from one or transmitters;
  • processing the detected radar radiation by aligning the signals to generate two or more aligned signals which are synthetically focused on a desired volume of the sample (or subject), and processing the aligned signals to generate part of the image of the sample (or subject).
  • steps i., ii. and iii. are repeated until an image of the sample (or subject) has been generated.
  • Medical imaging using radar is known in the art and would be familiar to the skilled person.
  • This type of imaging is sometimes referred to as microwave imaging, or ultrawideband (UWB) microwave imaging.
  • the range of frequencies used in radar imaging typically varies from 0.1-40 GHz, preferably 0.5-20 GHz.
  • Step c. is typically done using a computer processor which generates an image of the sample (or subject) on a display device such as a computer screen. Algorithms to process signals detected from the one or more detecting antenna(s) are known in the art and would be familiar to the skilled person.
  • Step c. preferably comprises generating an image of the sample (or subject) showing the distribution of the contrast agent in the sample (or subject).
  • the method preferably further comprises the step of administering the contrast agent to the sample (or subject).
  • the method preferably further comprises the step of using the image of the subject to diagnose a disease in the subject, preferably a human or non-human animal subject.
  • the sample used in the method can be part of a human or non-human animal body, or alternatively a inanimate tissue sample which has been taken from a human or non-human animal body.
  • the method may be carried out on a synthetic mimic of human or non-human animal tissue. Such synthetic analogues are typically called "phantoms" in the art.
  • sample and “subject” as used herein are generally interchangeable.
  • subject is however generally used when referring to animate or live samples, such as human or non-human animals which are being imaged.
  • the present invention also relates to an imaging apparatus comprising
  • one or more antennas capable of emitting radar radiation to a defined volume and receiving radar radiation that has passed through that volume; and a computer processor for processing the signals received by the one or more antennas to form an image of the defined volume.
  • the defined volume is sized to accommodate a human body.
  • the apparatus of the invention preferably also comprises a sample which contains the radar contrast agent, wherein at least part of the sample is located in the defined volume.
  • the sample is inanimate (i.e. does not form part of a living organism).
  • the apparatus of the invention preferably also comprises a means for administering the radar contrast agent to a human or non-human animal, such as a syringe, a catheter or an enema kit.
  • the invention provides the use of a physiologically tolerable agents, markers and contrast agents which are capable of changing the reflection properties of radar radiation in the human body after administration of the agent, preferably in diagnosis of a disease in a human or non-human animal.
  • diagnosis is preferably by mapping of disease tissue by radar and by monitoring the signal reflected from the human or non-human animal.
  • the present invention also relates to contrast agents for use in diagnosis of a human or nonhuman animal by radar imaging.
  • the sample is preferably not located in an external (or applied) magnetic field.
  • contrast agent organic iodinated agents
  • metal chelates metal chelates
  • gas gas
  • magnetic iron oxide particles inorganic salts
  • organic iodinated agents are concerned, particular mention should be made of those agents already proposed in the literature for use as X-ray contrast agents.
  • examples of such materials include many compounds with low toxicity and compounds may be selected which distribute preferentially within the body, e.g. which congregate at particular tissues, organs or tissue abnormalities or which are essentially confined to the circulatory system and act as blood pool agents.
  • X-ray contrast agents suited for use according to the present invention include in particular the iodinated contrast agents, especially those containing one or more, generally one or two, triiodophenyl groups in their structure.
  • the most preferred organic iodinated compounds to be used as markers and contrast agents for radar-based medical diagnosis are water-soluble agents comprising one or two benzene rings each substituteted with 3 iodine atoms.
  • the even more preferred agents are such agents without any charge in vivo; so- called non-ionic agents. These compounds have several alcohol groups to secure that the substances have high water-solubility without being a salt.
  • Preferred gents are the following compounds: diatrizoic acid, ioxaglinic acid, iomeprol, iobitriol, iohexol, iopamidol, iopentol, iodixanol, ioforminol, ioxaglate, ioxilan, iopromide, iotrolan, ioversol and iothalamate.
  • the even most preferred agents are the following compounds: iohexol, iopamidol, iopentol, iodixanol, ioforminol, ioxaglate, ioxilan, iopromide, iotrolan, ioversol and iothalamate.
  • Iohexol is the most preferred organic iodinated agent.
  • Particular organic iodinated compounds useful according to the invention thus, for example, include compounds described in US5,993,780 (Nycomed), US5,958,376 (Nycomed), US5,958,375 (Nycomed), US5,882,628 (Nycomed), US7,754,920 (GE Healthcare), UD7,662,859 (GE Healthcare), US7,592,482 (Bracco), US7,485,753 (GE Healthcare), US4,032,567 (Schering), US4,239,747 (Schering), US4,264,572 (Schering), US4,269,819 (Schering), US4,269,819 (Schering), US4,364,921 (Schering), US4,395,391 (Schering), US4,426,371 (Schering), US4,547,357 (Schering), US5,004,835 (Schering), US5,073,362 (Schering)US5, 183,654
  • the organic iodinated agents used in the present invention are preferably iodobenzene compounds (i.e. having iodine as a ring substituent on an aromatic C 6 ring), especially diiodo or more preferably triiodo benzene compounds, in particular diiodo and triiodo benzene compounds having the iodines at non- adjacent ring positions.
  • the iodobenzene ring is preferably also substituted by hydrophilic groups comprising one, two or three hydroxyl groups. Preferred hydrophilic groups include
  • X is a Ci-6 alkylene group, especially an ethylene and more especially propylene group
  • R 1 is hydrogen or a methyl group
  • n 1 , 2, or 3, preferably 2 or 3.
  • the most preferred iodinated agents are;
  • Metal Chelates Insofar as metal chelates are concerned, particular mention should be made of theoe agents already proposed in the literature for use as MRI contrast agents. Examples of such materials include many compounds with low toxicity and compounds may be selected which distribute preferentially within the body, e.g. which congregate at particular tissues, organs or tissue abnormalities or which are essentially confined to the circulatory system and act as blood pool agents.
  • metal chelates suited for use according to the present invention include in particular paramagnetic chelates especially gadolinium chelates, dysprosium chelates, iron chelates and manganese chelates, especially those containing a chelating agent being an amino acid derivative like for example derivatives of EDTA, DTPA, DPDP, DOTA and D03A.
  • the most preferred metal chelates to be used as markers and contrast agents for radar-based medical diagnosis are water-soluble agents comprising gadolinium (3+) or manganese (2+). Both non-ionic chelates and ionic chelates are among the most preferred chelates for use as markers and contrast agents for radar-based medical diagnosis.
  • the even most preferred chelates are the following compounds: GdDTPA
  • Gdopentetate dimeglumine dimeglumine
  • GdDOTA glycoteric acid meglumine
  • GdDTPA-BMA gadodiamide
  • Gd2HP-D03A gadoteridol
  • MnDPDP mangafodipir
  • Non-ionic chelates are used as pharmaceutically acceptable salts like sodium salt, potassium salt or meglumine salt.
  • the most preferred chelates are:
  • Particular metal chelates useful according to the invention thus, for example, include compounds described in US7.767.196 (University of Hong Kong), US7,745,590 (University of Utah), US7,368,099 (Kyushu University), US4,647,447 (Schering), US4,957,939 (Schering), US4,963,344 (Schering), US 5,021 ,236 (Schering), US5,098,692 (Schering), US5, 277,895 (Schering), US5,316,756 (Schering), US5,334,371 (Schering), US5,362,475 (Schering), US5,403,572 (Schering), US5.419,894 (Schering), US5,560,903 (Schering), US5,595,725 (Schering), US4.916,246 (Bracco), US4,980,502 (Bracco), US5, 132,409 (Bracco), US5, 182,370 (Bracco), US
  • gases are concerned, particular mention should be made of those agents already proposed in the literature for use as ultrasound contrast agents and to some extent for use as gastrointestinal X-ray contrast agents.
  • examples of such materials include many compounds with low toxicity, low solubility in blood and compounds may be selected which distribute preferentially within the body, e.g. which congregate at particular tissues, organs or tissue abnormalities or which are essentially confined to the circulatory system and act as blood pool agents.
  • gases suited for use according to the present invention include in air, sulfurhexafluoride and perfluorocarbons; for use within the vascular system gases with low solubility in blood are the most preferred gases.
  • Perfluorocarbons such as perfluoropropane and perfluorobutane are particularly preferred. The even most preferred gases for intravascular administration are
  • Perfluoropropane is the most preferred gas.
  • the most preferred agents gases for intravascular administration are preferably encapsulated into surfactants, phospholipids, carbohydrates, albumin or synthetic or semisynthetic polymer materials.
  • the even most preferred gas-based products according to the present invention are products like SonoVue, Sonazoid, Optison and Levovist.
  • Encapsulated gas-based compositions useful according to the invention thus, for example, include compounds described in US 6,221 ,337 (Nycomed), US6,274,120 (Nycomed), US5,674,468 (Nycomed), US5,670, 135 (Nycomed), US5,648,062 (Nycomed), US5,637,289 (Nycomed), US5,618,514 (Nycomed), US5,614, 169 (Nycomed), US5,569,449 (Nycomed), US5,567,412 (Nycomed), US5,558,856 (Nycomed), US5,558,857 (Nycomed), US5,536,490 (Nycomed), US5,529,766 (Nycomed), US6.217,850 (Nycomed), US6, 177,061 (Nycomed), US6,165,442 (Nycomed), US6, 110,44
  • Magnetic Iron Oxide Insofar as magnetic iron oxides are concerned, particular mention should be made of those agents already proposed in the literature for use as MRI contrast agents. Examples of such materials include any particulate ferromagnetic or
  • superparamagnetic material which distribute preferentially within the body, e.g. which congregate at particular tissues, organs or tissue abnormalities or which are essentially confined to the circulatory system and act as blood pool agents.
  • magnétique iron oxides suited for use according to the present invention include any particulate iron oxide like magnetite (Fe304) or gamma-iron(lll)oxide. Both the particle size and the size of the iron oxide crystals might vary over a large range from a few nanometers to micrometers.
  • the iron oxide material might be encapsulated or coated with various organic materials like for example natural polymers, synthetic polymers, proteins, carbohydrates, polyethyleneglycols and other materials.
  • the even most preferred magnetic iron oxide-based products according to the present invention are products like Endorem (Feridex), Resovist, Sinerem, Combidex and Cliavist.
  • Iron oxide based compositions useful according to the invention thus, for example, include compounds described in US6, 123,920 (Nycomed), US5,545,395 (Bracco), US7,807,137 (University of Puerto Rico), US4,452,773 (Advanced Magnetics), US4,770,183 (Advanced Magnetics), US4,827,945 (Advanced Magnetics), US5, 102,652 (Advanced Magnetics), US5, 160,726 (Advanced Magnetics),
  • inorganic salts are concerned, particular mention should be made of those agents already proposed in the literature for use as X-ray contrast agents. Examples of such materials include any particulate insoluble material like for example barium sulphate. Inorganic salts are preferably administered directly into the gastrointestinal system by oral administration or by use of an enema
  • Barium salts are particularly preferred inorganic salts, with barium sulphate being the most preferred.
  • One further aspect of the present invention relates to use of liposome markers or as contrast agent in radar-based medical imaging. Liposomes are for example described in US6.217,849 (Bracco), US5,980,937 (Bracco), US5,702,722 (Bracco), US5,676,928 (Nycomed), US7,588,751 (Konica Minolta) and US7,785,568 (Marval Biosciences).
  • One further aspect of the present invention relates to use of targeted markers or as contrast agent in radar-based medical imaging.
  • Targeted markers and contrast agents are for example described in US6,051 ,207 (Nycomed), US6,264,917 (Nycomed), US5,414, 114 (Bracco), US6, 139,819 (lmaRx),US6,261 ,537
  • contrast agents have a Fresnel reflection coefficient of at least 0.15, more preferably at least 0.20, at frequencies of between 0.5 and 20 GHz (e.g. 5 GHz) with reference to healthy human blood as measured using a Agilent Network Analyzer N5245A at concentrations of 300 mg/ml.
  • healthy human blood blood that has recently been taken from a healthy human adult in which all blood markers such as platelet count, ion levels etc are within what would generally be deemed to be normal levels by a physician.
  • Particulate contrast agents for parenteral administration should preferably have particle sizes of no more than 1.5 micrometer, especially 1.0 micrometer or less.
  • Enteral administration of markers and contrast agents for radar based medical diagnosis including radar based medical imaging will preferably be by oral administration of the marker or contrast agent or by administration of the marker or contrast agent using an enema.
  • contrast agents according to the invention will generally be by injection or infusion, especially into the cardiovascular system.
  • markers or contrast media may also be administered into body cavities having external voidance ducts, e.g. by catheter into the bladder, uterus etc.
  • the dosages of markers and contrast agents for radar-based medical diagnosis used according to the invention will vary over a broad range depending on a variety of factors such as administration route, the pharmacodynamic properties of the contrast agent (the more widely distributing the agent is the larger the dose may be), the chemical and physical nature of the contrast agent, and the frequency of the electrical current applied in the impedance measurement.
  • agents will be administered in concentrations of 1 micromol/l to 1 mol/l, preferably 0.01 to 0.8 mmol/l and dosages will lie in the range 0.002 to 20 mmol/kg bodyweight, generally 0.005 to 10 mmol/kg.
  • the overall dosage will generally be 1 to 200 ml when administered into the cardiovascular system or 5 ml to 1.5 litres of marker or contrast agent when administered into a body cavity having an external voidance duct, e.g. by oral or rectal administration.
  • the markers and contrast agents according to the present invention may be used for a wide range of clinical indications with appropriate selection of the contrast agent (for its pharmacodynamic properties) and of the administration route.
  • non-absorbable markers and contrast agents for radar-based medical diagnosis are particularly useful in the gastrointestinal tract, for diagnosis of abnormalities therein or as markers of the gastrointestinal system.
  • Such agents may also be used for dynamic studies, for example of gastric emptying.
  • a pH control agent such as cimetidine to suppress naturally occuring pH variations which might otherwise reduce imaging accuracy.
  • Some of the marker and contrast agents are absorbable from the gastrointestinal trace and may be taken up by the liver and excreted into the bile. Such agents can thus be used for imaging the hepatobiliary system and for liver function studies even following oral rather than parenteral administration.
  • contrast may be enhanced by administration of a
  • physiologically active agent which serves to modify body fluid distribution, e.g. a diuretic, thereby causing image modification in body areas where body fluid is increased or decreased.
  • a physiologically active agent which serves to modify body fluid distribution, e.g. a diuretic, thereby causing image modification in body areas where body fluid is increased or decreased.
  • Preferred methods and uses described above utilise the preferred contrast agents mentioned herein.
  • preferred diseases are those diseases mentioned herein, such as diseases selected from abnormalities in the gastrointestinal tract, cancer and tumours such as for example breast cancer, lung cancer, liver cancer, metastisis, brain cancer and colorectal cancer; and infarcts or other cardiovascular diseases or cardiovascular events such as in the heart infarcts.
  • Example 1 lodinated marker and contrast agent for radar-based diagnosis including imaging
  • a solution of iohexol (Omnipaque) (300 mg /ml, 50 ml) is administered
  • the patient undergoes a radar-based diagnosis of the heart and the kidneys.
  • Gas-based marker and contrast agent for radar-based diagnosis including imaging
  • a suspension of encapsulated perfluoropropane (Optison) (0.19 mg/ml, 3 ml) is administered intravenously to a patient.
  • the patient undergoes a radar-based diagnosis of the cardiovascular system.
  • Optison encapsulated perfluoropropane
  • Metal chelate marker and contrast agent for radar-based diagnosis including imaging
  • GdDTPA bis-meglumine salt (Magnevist) (0.5 mmol/ml), 16 ml) is administered intravenouly to a patient.
  • the patient undergoes a radar-based diagnosis of the heart, brain and the renal system.
  • Magnetic iron oxide-based marker and contrast agent for radar-based diagnosis including imaging Magnetic iron oxide particles (Resovist) (0.25 mmol/ml, 10 ml) is administered intravenously to a patient. The patient undergoes a radar-based diagnosis of the cardiovascular system.
  • Imaging Magnetic iron oxide particles Repsovist
  • Inorganic salt marker and contrast agent for radar-based diagnosis including imaging
  • Barium sulphate (1 gram/ml, 400 ml) is administered as an enema to a patient. The patient undergoes a radar-based diagnosis of abdomen.
  • the permittivity is a measure of how the electrical field is affected by or affects the medium.
  • the permittivity in various contrast agents was determined using Agilent Network Analyzer N5245A with Agilent 5070E dielectric probe kit. (Agilent Technologies, USA).
  • the contrast agents were the following:
  • Particulate x-ray contrast agent Barium sulfate suspension: 40% w/v (30% v/v) (Tagitol-V (E-Z-EM, Canada)).
  • Ionic iodinated X-ray contrast agent 270 mg l/ml (diatrizoate sodium 100 mg/ml and diatrizoate meglumine 600 mg/ml, Gastrografin (Bayer Schering Pharma, Germany))
  • Non-ionic iodinated X-ray contrast agent 350 mgl/ml (iohexol.( Omnipaque. GE Healthcare, USA))
  • the conductivity in various contrast agents was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA).
  • the permittivity in dilued Multihance was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA).
  • the permittivity in dilued Gastrografin was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA).
  • the conductivity of diluted Gastrografin was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA). The conductivity data on diluted Gastrografin are shown in Figure 1 1 and Figure 12.
  • the permittivity in dilued Omnipaque was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA).
  • the conductivity of diluted Omnipaque was determined using Agilent Network Analyzer N5245A with Agilent (5070E dielectric probe kit.(Agilent Technologies, USA).
  • Omnipaque (iohexol) shows a surprisingly high Fresnel reflection coefficient.

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Abstract

La présente invention porte sur l'utilisation d'agents de contraste en imagerie à base de radar, en particulier en imagerie médicale. L'invention porte également sur l'utilisation d'agents de contraste dans le diagnostic de différentes maladies utilisant une technologie à base de radar. L'invention porte également sur un appareil pour imagerie à base de radar comprenant un agent de contraste.
PCT/EP2012/056363 2011-04-07 2012-04-05 Agents pour un diagnostic par radar médical Ceased WO2012136813A2 (fr)

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Citations (126)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4006743A (en) 1973-01-15 1977-02-08 The Johns Hopkins University System for continuous withdrawal of blood
US4032567A (en) 1972-02-16 1977-06-28 Schering Aktiengesellschaft Triiodoisophthalic acid monoamino acid amides, process for the preparation thereof, and use thereof as x-ray contrast media
US4125599A (en) 1976-08-19 1978-11-14 Mallinckrodt, Inc. X-ray contrast agents
US4139605A (en) 1977-03-28 1979-02-13 Bracco Industria Chimica S.P.A. Water-soluble, non-ionizing, radiopaque compounds and contrast compositions containing the same
US4239747A (en) 1976-06-23 1980-12-16 Schering Aktiengesellschaft Dicarboxylic acid bis(3,5-dicarbamoyl-2,4,6-triiodoanilides) useful as x-ray contrast agents
US4264572A (en) 1978-11-30 1981-04-28 Schering Aktiengesellschaft X-ray contrast media
US4269819A (en) 1978-07-14 1981-05-26 Schering Aktiengesellschaft 2,4,6-Triiodobenzonitrile derivatives and X-ray contrast media comprising them
US4348377A (en) 1979-08-09 1982-09-07 Bracco Industria Chimica S.P.A. New derivatives of 2,4,6-triiodo-isophthalic acid, proceses for their synthesis and X-ray contrasting materials containing these
US4352788A (en) 1979-08-09 1982-10-05 Bracco Industria Chimica S.P.A. Derivatives of 2,4,6-triiodo-isophthalic acid, processes for their synthesis and X-ray contrasting materials containing these
US4364921A (en) 1979-03-08 1982-12-21 Schering, Aktiengesellschaft Novel triiodinated isophthalic acid diamides as nonionic X-ray contrast media
US4395391A (en) 1980-11-25 1983-07-26 Schering Aktiengesellschaft Unsymmetrically substituted dicarboxylic-acid-bis-(2,4,6-triiodo-anilides), their preparation, and x-ray contrast media containing same
US4396598A (en) 1982-01-11 1983-08-02 Mallinckrodt, Inc. Triiodoisophthalamide X-ray contrast agent
US4426371A (en) 1980-10-10 1984-01-17 Schering, Aktiengesellschaft Novel N-hydroxyalkylated dicarboxylic acid bis(3,5-dicarbamoyl-2,4,6-triiodoanilides), as X-ray contrast media
US4452773A (en) 1982-04-05 1984-06-05 Canadian Patents And Development Limited Magnetic iron-dextran microspheres
US4547357A (en) 1981-12-18 1985-10-15 Schering, Aktiengesellschaft N-Hydroxyethylated 2,4,6-triiodoaminoisophthalic acid bistrihydroxybutylamides, their preparation and x-ray contrast media containing them
US4647447A (en) 1981-07-24 1987-03-03 Schering Aktiengesellschaft Diagnostic media
US4770183A (en) 1986-07-03 1988-09-13 Advanced Magnetics Incorporated Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
US4827945A (en) 1986-07-03 1989-05-09 Advanced Magnetics, Incorporated Biologically degradable superparamagnetic materials for use in clinical applications
US4916246A (en) 1986-01-30 1990-04-10 Bracco Chimica S.P.A. Paramagnetic chelates useful for NMR imaging
US4957939A (en) 1981-07-24 1990-09-18 Schering Aktiengesellschaft Sterile pharmaceutical compositions of gadolinium chelates useful enhancing NMR imaging
US5004835A (en) 1987-11-16 1991-04-02 Schering Aktiengesellschaft Substituted dicarboxylic acid-bis(3,5-dicarbamoyl-2,4,6-triiodoanilides), process for their production as well as X-ray contrast media containing them
US5019371A (en) 1990-11-21 1991-05-28 Mallinckrodt Medical, Inc. Novel x-ray contrast agents, compositions and methods
US5030956A (en) 1989-04-25 1991-07-09 Murphy Quentin M Radar tomography
US5073362A (en) 1987-09-17 1991-12-17 Schering Aktiengesellschaft Dicarboxylic acid-bis(3,5-dicarbamoyl-2,4,6-triiodoanilides) and x-ray contrast media containing them
US5075502A (en) 1989-12-13 1991-12-24 Mallinckrodt, Inc. Nonionic x-ray contrast agents, compositions and methods
US5098692A (en) 1986-11-28 1992-03-24 Schering Aktiengellschaft Calcium chelate and gadolinium pharmaceutical composition and methods of x-ray and nmr imaging
US5102652A (en) 1986-07-03 1992-04-07 Advanced Magnetics Inc. Low molecular weight carbohydrates as additives to stabilize metal oxide compositions
US5132409A (en) 1987-01-12 1992-07-21 Bracco Industria Chimica S.P.A. Macrocyclic chelating agents and chelates thereof
US5141738A (en) 1983-04-15 1992-08-25 Schering Aktiengesellschaft Ultrasonic contrast medium comprising gas bubbles and solid lipophilic surfactant-containing microparticles and use thereof
US5160726A (en) 1990-02-15 1992-11-03 Advanced Magnetics Inc. Filter sterilization for production of colloidal, superparamagnetic MR contrast agents
US5183654A (en) 1989-11-03 1993-02-02 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5191120A (en) 1989-12-13 1993-03-02 Mallinckrodt Medical, Inc. Process for preparing nonionic X-ray contrast agents
US5204086A (en) 1982-10-01 1993-04-20 Nycomed Imaging As X-ray contrast agent
US5204457A (en) 1989-10-20 1993-04-20 Meito Sangyo Kabushiki Kaisha Organic magnetic complex
US5232685A (en) 1989-11-03 1993-08-03 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5262176A (en) 1986-07-03 1993-11-16 Advanced Magnetics, Inc. Synthesis of polysaccharide covered superparamagnetic oxide colloids
US5277895A (en) 1990-11-08 1994-01-11 Schering Aktiengesellschaft Mono-n-substituted 1,4,7,10-tetraazacyclododecane derivatives, process for their production and pharmaceutical agents containing these derivatives
US5316756A (en) 1983-07-01 1994-05-31 Schering Aktiengesellschaft NMR imaging using paramagnetic chelates having hydroxyalkyl-substituted amide groups
US5334371A (en) 1988-07-20 1994-08-02 Schering Aktiengesellschaft Marcocyclic polyaza bicyclo compounds containing 5 or 6 membered rings, and method for MRI
US5349085A (en) 1982-11-08 1994-09-20 Nycomed Imaging As X-ray contrast agents
US5352436A (en) 1992-11-02 1994-10-04 Drexel University Surfactant-stabilized microbubble mixtures, process for preparing and methods of using the same
US5356613A (en) 1991-03-18 1994-10-18 Mallinckrodt Medical, Inc. X-ray contrast agents, compositions and methods
US5380519A (en) 1990-04-02 1995-01-10 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US5413774A (en) 1992-01-23 1995-05-09 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US5414114A (en) 1991-07-22 1995-05-09 Bracco International B.V. Method for making conjugate moieties capable of chelating paramagnetic metals and designed for coupling with a factor responsive to specific cellular marker sites
US5425366A (en) 1988-02-05 1995-06-20 Schering Aktiengesellschaft Ultrasonic contrast agents for color Doppler imaging
US5445813A (en) 1992-11-02 1995-08-29 Bracco International B.V. Stable microbubble suspensions as enhancement agents for ultrasound echography
US5474756A (en) 1986-01-23 1995-12-12 Bracco International B.V. Method for imaging mammalian tissue using 1-substituted-1,4,7-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs
US5529766A (en) 1991-03-28 1996-06-25 Nycomed Imaging As Contrast agents
US5536490A (en) 1991-03-28 1996-07-16 Nycomed Imaging As Contrast agents
US5545395A (en) 1992-08-13 1996-08-13 Bracco Research, S.A. Method of imaging using encapsulated magnetite particles
US5556610A (en) 1992-01-24 1996-09-17 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
US5558856A (en) 1992-01-09 1996-09-24 Nycomed Imaging As Microbubble-generating contrast agents for ultrasound and magnetic resonance imaging
US5558857A (en) 1991-06-03 1996-09-24 Nycomed Imaging As Contrast agents
US5560903A (en) 1981-07-24 1996-10-01 Schering Aktiengesellschaft Method of enhancing paramagnetism in chelates for MRI
US5567412A (en) 1992-01-09 1996-10-22 Nycomed Imaging As Contrast agents consisting of galactose particles and an amphilic carboxylic acid
US5573751A (en) 1991-09-17 1996-11-12 Sonus Pharmaceuticals, Inc. Persistent gaseous bubbles as ultrasound contrast media
US5585112A (en) 1989-12-22 1996-12-17 Imarx Pharmaceutical Corp. Method of preparing gas and gaseous precursor-filled microspheres
US5591846A (en) 1989-11-29 1997-01-07 Bracco International B.V. Nonionic radiographic contrast agents
US5618514A (en) 1983-12-21 1997-04-08 Nycomed Imaging As Diagnostic and contrast agent
US5648062A (en) 1992-01-09 1997-07-15 Nycomed Imaging As Contrast agents consisting of galactose particles
US5656211A (en) 1989-12-22 1997-08-12 Imarx Pharmaceutical Corp. Apparatus and method for making gas-filled vesicles of optimal size
US5674468A (en) 1992-03-06 1997-10-07 Nycomed Imaging As Contrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons
US5676928A (en) 1994-03-28 1997-10-14 Nycomed Imaging As Liposomes
US5689002A (en) 1995-09-08 1997-11-18 Bracco International B.V. Process for the crystallization from water of (S)-N,N'-bis 2-hydroxy-1-(hydroxymethyl)ethyl!-5- 2-hydroxy-1-oxopropyl)amino!-2,4,6-triiodo-1,3-benzendicarboxamide
US5702722A (en) 1994-09-30 1997-12-30 Bracco Research S.A. Liposomes with enhanced entrapment capacity, method and use
US5711933A (en) 1990-05-18 1998-01-27 Bracco International B.V. Method of making polymeric gas or air filled microballoons for ultrasonic echography
US5827504A (en) 1994-12-16 1998-10-27 Bracco Research S.A. Method of echographic imaging using frozen gasbubble suspensions
US5846518A (en) 1992-12-16 1998-12-08 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media contrast agents containing the media and method
US5856570A (en) 1994-11-29 1999-01-05 Bracco International B.V. Process for preparing 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of the corresponding acid in the presence of a tertiary amine salt or quaternary ammonium salt
US5882628A (en) 1994-09-23 1999-03-16 Nycomed Imaging As Contrast media
US5928626A (en) 1992-01-09 1999-07-27 Nycomed Imaging As Contrast agents, consisting of carbohydrate particles
US5958375A (en) 1994-09-23 1999-09-28 Nycomed Imaging As Urea-linked, iodinated bis phenyl compounds for X-ray contrast media
US5958373A (en) 1993-09-07 1999-09-28 Nycomed Salutar Inc. Polychelants as contrast enhancing agents
US6045777A (en) 1997-06-30 2000-04-04 Acusphere, Inc. Method for enhancing the echogenicity and decreasing the attenuation of microencapsulated gases
US6051207A (en) 1996-10-28 2000-04-18 Nycomed Imaging As Contrast agents
US6054118A (en) 1997-01-22 2000-04-25 Nycomed Imaging As Contrast agents comprising two types of gas-containing microparticles
US6110444A (en) 1994-03-01 2000-08-29 Nycomed Imaging As Gas-containing microcapsules useful as contrast agents for diagnostic imaging
US6123920A (en) 1996-01-10 2000-09-26 Nycomed Imaging As Superparamagnetic contrast media coated with starch and polyalkylene oxides
US6139819A (en) 1995-06-07 2000-10-31 Imarx Pharmaceutical Corp. Targeted contrast agents for diagnostic and therapeutic use
US6146657A (en) 1989-12-22 2000-11-14 Imarx Pharmaceutical Corp. Gas-filled lipid spheres for use in diagnostic and therapeutic applications
US6165442A (en) 1996-02-19 2000-12-26 Nycomed Imaging As Thermally stabilized ultrasound contrast agent
US6165378A (en) 1996-08-30 2000-12-26 Meito Sangyo Kabushiki Kaisha Polysaccharide derivative/magnetic metal oxide composite
US6177061B1 (en) 1997-04-23 2001-01-23 Nycomed Imaging As Contrast agents comprising an azeotropic mixture of two gases for ultrasound investigations
US6217850B1 (en) 1995-06-07 2001-04-17 Nycomed Imaging As Method of making lyophilized microbubble compositions useful as contrast agents
US6217849B1 (en) 1993-09-29 2001-04-17 Bracco Research S.A. Liposome suspensions as blood pool imaging contrast agents
US6221337B1 (en) 1996-02-19 2001-04-24 Nycomed Imaging As Microbubbles surrounded by a monolayer of negatively charged phospholipids as contrast agents
US6261537B1 (en) 1996-10-28 2001-07-17 Nycomed Imaging As Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors
US6264959B1 (en) 1988-02-05 2001-07-24 Schering Aktiengesellschaft Ultrasonic contrast agents, process for their preparation and their use as a diagnostic and therapeutic agent
US6264917B1 (en) 1996-10-28 2001-07-24 Nycomed Imaging As Targeted ultrasound contrast agents
US6274120B1 (en) 1994-02-15 2001-08-14 Nycomed Imaging As Dry microparticles for use as a contrast agent
US6310243B1 (en) 1994-09-23 2001-10-30 Nycomed Imaging As Iodinated x-ray contrast media
US6315981B1 (en) 1989-12-22 2001-11-13 Imarx Therapeutics, Inc. Gas filled microspheres as magnetic resonance imaging contrast agents
US6331289B1 (en) 1996-10-28 2001-12-18 Nycomed Imaging As Targeted diagnostic/therapeutic agents having more than one different vectors
US6350908B1 (en) 1998-09-11 2002-02-26 Bracco Imaging S.P.A Process for the preparation of S-N,N′-bis [2-hydroxy-1-(hydroxymethyl) ethyl]-5- [(2-hydroxy-1-oxopropyl) amino]-2,4,6-triiodo-1,3-benzenedicarboxamide
US6406680B1 (en) 1999-09-17 2002-06-18 Nycomed Imaging As X-ray contrast agents
US6420603B1 (en) 1998-11-27 2002-07-16 Bracco International B.V. Process for the preparation of n,n'-bis[2,3-dihydroxypropyl]-5-[(hydroxyacetyl) methylamino]-2, 4,6-triiodo-1, 3-benzenedi carboxamide
US6506938B1 (en) 1993-07-30 2003-01-14 Bracco International B.V. Process for the purifying of iopamidol
US6521211B1 (en) 1995-06-07 2003-02-18 Bristol-Myers Squibb Medical Imaging, Inc. Methods of imaging and treatment with targeted compositions
US6528039B2 (en) 1991-04-05 2003-03-04 Bristol-Myers Squibb Medical Imaging, Inc. Low density microspheres and their use as contrast agents for computed tomography and in other applications
US6548047B1 (en) 1997-09-15 2003-04-15 Bristol-Myers Squibb Medical Imaging, Inc. Thermal preactivation of gaseous precursor filled compositions
US6551576B1 (en) 1989-12-22 2003-04-22 Bristol-Myers Squibb Medical Imaging, Inc. Container with multi-phase composition for use in diagnostic and therapeutic applications
US6613306B1 (en) 1990-04-02 2003-09-02 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US20040019282A1 (en) 2002-07-29 2004-01-29 Mullen Linda J. Hybrid lidar-radar for medical diagnostics
US20040249257A1 (en) 2003-06-04 2004-12-09 Tupin Joe Paul Article of manufacture for extracting physiological data using ultra-wideband radar and improved signal processing techniques
US7083778B2 (en) 1991-05-03 2006-08-01 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US7115778B2 (en) 1999-02-26 2006-10-03 Bracco Imaging, S.P.A. Process for the preparation of iopamidol
US7182934B2 (en) 1996-10-28 2007-02-27 Ge Healthcare As Contrast agents
US7368099B2 (en) 2003-02-27 2008-05-06 Kyushu University, National University Corporation MRI contrast agents
US7374745B2 (en) 1998-10-12 2008-05-20 Mallinckrodt, Inc. Ultrasound contrast agents
US7413727B2 (en) 1997-04-24 2008-08-19 Ge Healthcare As Contrast agents
US7485753B2 (en) 2005-12-02 2009-02-03 Ge Healthcare As Contrast agents
US20090192384A1 (en) 2008-01-30 2009-07-30 Siemens Aktiengesellschaft Medical unit and method for improving examination and treatment workflows
US7588751B2 (en) 2004-07-21 2009-09-15 Konica Minolta Medical & Graphic, Inc. Liposome-containing radiographic contrast medium and preparation method thereof
US7592482B2 (en) 2005-09-13 2009-09-22 Bracco Imaging S.P.A. Process for the preparation of contrast agents
US7745590B1 (en) 2001-11-13 2010-06-29 University Of Utah Research Foundation Degradable macromolecular magnetic resonance imaging contrast agents and methods thereof
US7754920B1 (en) 2009-07-21 2010-07-13 Ge Healthcare As Solvent reduction in crystallisation of intermediate for non-ionic X-ray contrast agents
US7767196B2 (en) 2005-11-21 2010-08-03 The University Of Hong Kong Optimized relaxivity and specificity hepatobiliary MRI contrast agent
US7785568B2 (en) 2004-04-21 2010-08-31 Marval Biosciences, Inc. Compositions and methods for enhancing contrast in imaging
US7807137B1 (en) 1998-12-22 2010-10-05 University Of Puerto Rico Iron-based contrast agent
WO2010124117A2 (fr) 2009-04-22 2010-10-28 Lifewave, Inc. Dispositif et procédés de contrôle foetal
US20100292559A1 (en) 2009-05-14 2010-11-18 Thilo Hannemann Radar-equipped patient bed for a medical imaging apparatus, and operating method therefor
US20100322868A1 (en) 2007-07-12 2010-12-23 Mikkel Thaning Contrast agents
US7871597B2 (en) 1999-04-09 2011-01-18 Amag Pharmaceuticals, Inc. Polyol and polyether iron oxide complexes as pharmacological and/or MRI contrast agents
US7892520B2 (en) 2006-07-31 2011-02-22 The Hong Kong University Of Science And Technology Solid-state synthesis of iron oxide nanoparticles
US7892522B2 (en) 1996-08-02 2011-02-22 Ge Healthcare As Contrast agents

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9712524D0 (en) * 1997-06-16 1997-08-20 Nycomed Imaging As Method
DE102008064400A1 (de) * 2008-06-02 2009-12-03 Rohde & Schwarz Gmbh & Co. Kg Mikrowellenuntersuchung mit einem Kontrastmittel
GB0920839D0 (en) * 2009-11-27 2010-01-13 Univ Bristol Contrast agents for medical imaging

Patent Citations (172)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4032567A (en) 1972-02-16 1977-06-28 Schering Aktiengesellschaft Triiodoisophthalic acid monoamino acid amides, process for the preparation thereof, and use thereof as x-ray contrast media
US4006743A (en) 1973-01-15 1977-02-08 The Johns Hopkins University System for continuous withdrawal of blood
US4239747A (en) 1976-06-23 1980-12-16 Schering Aktiengesellschaft Dicarboxylic acid bis(3,5-dicarbamoyl-2,4,6-triiodoanilides) useful as x-ray contrast agents
US4125599A (en) 1976-08-19 1978-11-14 Mallinckrodt, Inc. X-ray contrast agents
US4160015A (en) 1976-08-19 1979-07-03 Mallinckrodt, Inc. 2,4,6-Triiodobenzoic acid derivatives and their use as x-ray contrast agents
US4139605A (en) 1977-03-28 1979-02-13 Bracco Industria Chimica S.P.A. Water-soluble, non-ionizing, radiopaque compounds and contrast compositions containing the same
US4269819A (en) 1978-07-14 1981-05-26 Schering Aktiengesellschaft 2,4,6-Triiodobenzonitrile derivatives and X-ray contrast media comprising them
US4264572A (en) 1978-11-30 1981-04-28 Schering Aktiengesellschaft X-ray contrast media
US4364921A (en) 1979-03-08 1982-12-21 Schering, Aktiengesellschaft Novel triiodinated isophthalic acid diamides as nonionic X-ray contrast media
US4348377A (en) 1979-08-09 1982-09-07 Bracco Industria Chimica S.P.A. New derivatives of 2,4,6-triiodo-isophthalic acid, proceses for their synthesis and X-ray contrasting materials containing these
US4352788A (en) 1979-08-09 1982-10-05 Bracco Industria Chimica S.P.A. Derivatives of 2,4,6-triiodo-isophthalic acid, processes for their synthesis and X-ray contrasting materials containing these
US4426371A (en) 1980-10-10 1984-01-17 Schering, Aktiengesellschaft Novel N-hydroxyalkylated dicarboxylic acid bis(3,5-dicarbamoyl-2,4,6-triiodoanilides), as X-ray contrast media
US4395391A (en) 1980-11-25 1983-07-26 Schering Aktiengesellschaft Unsymmetrically substituted dicarboxylic-acid-bis-(2,4,6-triiodo-anilides), their preparation, and x-ray contrast media containing same
US5595725A (en) 1981-07-24 1997-01-21 Schering Aktiengesellschaft Diagnostic media
US4647447A (en) 1981-07-24 1987-03-03 Schering Aktiengesellschaft Diagnostic media
US5560903A (en) 1981-07-24 1996-10-01 Schering Aktiengesellschaft Method of enhancing paramagnetism in chelates for MRI
US5362475A (en) 1981-07-24 1994-11-08 Schering Aktiengesellschaft Gadolinium chelates for magnetic resonance imaging
US4957939A (en) 1981-07-24 1990-09-18 Schering Aktiengesellschaft Sterile pharmaceutical compositions of gadolinium chelates useful enhancing NMR imaging
US4963344A (en) 1981-07-24 1990-10-16 Schering Aktiengesellschaft Method to enhance NMR imaging using chelated paramagnetic ions
US4963344B1 (fr) 1981-07-24 1992-08-25 Schering Ag
US5021236A (en) 1981-07-24 1991-06-04 Schering Aktiengesellschaft Method of enhancing NMR imaging using chelated paramagnetic ions bound to biomolecules
US4547357A (en) 1981-12-18 1985-10-15 Schering, Aktiengesellschaft N-Hydroxyethylated 2,4,6-triiodoaminoisophthalic acid bistrihydroxybutylamides, their preparation and x-ray contrast media containing them
US4396598A (en) 1982-01-11 1983-08-02 Mallinckrodt, Inc. Triiodoisophthalamide X-ray contrast agent
US4452773A (en) 1982-04-05 1984-06-05 Canadian Patents And Development Limited Magnetic iron-dextran microspheres
US5204086A (en) 1982-10-01 1993-04-20 Nycomed Imaging As X-ray contrast agent
US5349085A (en) 1982-11-08 1994-09-20 Nycomed Imaging As X-ray contrast agents
US5141738A (en) 1983-04-15 1992-08-25 Schering Aktiengesellschaft Ultrasonic contrast medium comprising gas bubbles and solid lipophilic surfactant-containing microparticles and use thereof
US5316756A (en) 1983-07-01 1994-05-31 Schering Aktiengesellschaft NMR imaging using paramagnetic chelates having hydroxyalkyl-substituted amide groups
US5419894A (en) 1983-07-01 1995-05-30 Schering Aktiengesellschaft Complexing agents, complexes and complex salts
US5670135A (en) 1983-12-21 1997-09-23 Nycomed Imaging As Ultrasonic contrast agent comprising carbohydrate particles
US5618514A (en) 1983-12-21 1997-04-08 Nycomed Imaging As Diagnostic and contrast agent
US5674470A (en) 1986-01-23 1997-10-07 Bracco Diagnostics Inc. Method for imaging mammalian tissue using 1-substituted- 4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs
US5846519A (en) 1986-01-23 1998-12-08 Bracco Diagnostics Inc. Method for imaging mammalian tissue using 1-substituted-1,4,7-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs
US5474756A (en) 1986-01-23 1995-12-12 Bracco International B.V. Method for imaging mammalian tissue using 1-substituted-1,4,7-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs
US4980502A (en) 1986-01-30 1990-12-25 Bracco Industria Chimica, S.P.A. Paramagnetic chelates
US5182370A (en) 1986-01-30 1993-01-26 Bracco Industria Chimica S.P.A. Paramagnetic chelates
US4916246A (en) 1986-01-30 1990-04-10 Bracco Chimica S.P.A. Paramagnetic chelates useful for NMR imaging
US5262176A (en) 1986-07-03 1993-11-16 Advanced Magnetics, Inc. Synthesis of polysaccharide covered superparamagnetic oxide colloids
US5102652A (en) 1986-07-03 1992-04-07 Advanced Magnetics Inc. Low molecular weight carbohydrates as additives to stabilize metal oxide compositions
US4827945A (en) 1986-07-03 1989-05-09 Advanced Magnetics, Incorporated Biologically degradable superparamagnetic materials for use in clinical applications
US4770183A (en) 1986-07-03 1988-09-13 Advanced Magnetics Incorporated Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
US5098692A (en) 1986-11-28 1992-03-24 Schering Aktiengellschaft Calcium chelate and gadolinium pharmaceutical composition and methods of x-ray and nmr imaging
US5132409A (en) 1987-01-12 1992-07-21 Bracco Industria Chimica S.P.A. Macrocyclic chelating agents and chelates thereof
US5073362A (en) 1987-09-17 1991-12-17 Schering Aktiengesellschaft Dicarboxylic acid-bis(3,5-dicarbamoyl-2,4,6-triiodoanilides) and x-ray contrast media containing them
US5004835A (en) 1987-11-16 1991-04-02 Schering Aktiengesellschaft Substituted dicarboxylic acid-bis(3,5-dicarbamoyl-2,4,6-triiodoanilides), process for their production as well as X-ray contrast media containing them
US6264959B1 (en) 1988-02-05 2001-07-24 Schering Aktiengesellschaft Ultrasonic contrast agents, process for their preparation and their use as a diagnostic and therapeutic agent
US5425366A (en) 1988-02-05 1995-06-20 Schering Aktiengesellschaft Ultrasonic contrast agents for color Doppler imaging
US5403572A (en) 1988-07-20 1995-04-04 Schering Aktiengesellschaft Macrocyclic polyaza compounds containing 5 or 6 membered rings, process for producing them and pharmaceutical media containing them
US5334371A (en) 1988-07-20 1994-08-02 Schering Aktiengesellschaft Marcocyclic polyaza bicyclo compounds containing 5 or 6 membered rings, and method for MRI
US5030956A (en) 1989-04-25 1991-07-09 Murphy Quentin M Radar tomography
US5204457A (en) 1989-10-20 1993-04-20 Meito Sangyo Kabushiki Kaisha Organic magnetic complex
US5232685A (en) 1989-11-03 1993-08-03 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5183654A (en) 1989-11-03 1993-02-02 Schering Aktiengesellschaft Nonionic x-ray contrast medium with high iodine content
US5628980A (en) 1989-11-29 1997-05-13 Bracco International B.V. Nonionic radiographic contrast agents
US5591846A (en) 1989-11-29 1997-01-07 Bracco International B.V. Nonionic radiographic contrast agents
US5075502A (en) 1989-12-13 1991-12-24 Mallinckrodt, Inc. Nonionic x-ray contrast agents, compositions and methods
US5191120A (en) 1989-12-13 1993-03-02 Mallinckrodt Medical, Inc. Process for preparing nonionic X-ray contrast agents
US6146657A (en) 1989-12-22 2000-11-14 Imarx Pharmaceutical Corp. Gas-filled lipid spheres for use in diagnostic and therapeutic applications
US5656211A (en) 1989-12-22 1997-08-12 Imarx Pharmaceutical Corp. Apparatus and method for making gas-filled vesicles of optimal size
US6315981B1 (en) 1989-12-22 2001-11-13 Imarx Therapeutics, Inc. Gas filled microspheres as magnetic resonance imaging contrast agents
US6479034B1 (en) 1989-12-22 2002-11-12 Bristol-Myers Squibb Medical Imaging, Inc. Method of preparing gas and gaseous precursor-filled microspheres
US5585112A (en) 1989-12-22 1996-12-17 Imarx Pharmaceutical Corp. Method of preparing gas and gaseous precursor-filled microspheres
US6551576B1 (en) 1989-12-22 2003-04-22 Bristol-Myers Squibb Medical Imaging, Inc. Container with multi-phase composition for use in diagnostic and therapeutic applications
US5160726A (en) 1990-02-15 1992-11-03 Advanced Magnetics Inc. Filter sterilization for production of colloidal, superparamagnetic MR contrast agents
US5531980A (en) 1990-04-02 1996-07-02 Bracco International Bv Stable microbubbles suspensions injectable into living organisms
US7033574B1 (en) 1990-04-02 2006-04-25 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US5658551A (en) 1990-04-02 1997-08-19 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US6136293A (en) 1990-04-02 2000-10-24 Bracco International B.V. Stable microbubbles suspensions containing saturated lamellar phospholipids
US6613306B1 (en) 1990-04-02 2003-09-02 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US5911972A (en) 1990-04-02 1999-06-15 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US5643553A (en) 1990-04-02 1997-07-01 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US5380519A (en) 1990-04-02 1995-01-10 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US6110443A (en) 1990-04-02 2000-08-29 Bracco International N.V. Dry stable formation to produce microbubble suspension for ultrasound
US5567414A (en) 1990-04-02 1996-10-22 Bracco International B.V. Stable microbubbles suspensions injectable into living organisms
US6139818A (en) 1990-05-18 2000-10-31 Bracco International B.V. Method of making ultrasonic contrast agent
US6200548B1 (en) 1990-05-18 2001-03-13 Bracco International B.V. Gas or air filled polymeric microballoons
US5711933A (en) 1990-05-18 1998-01-27 Bracco International B.V. Method of making polymeric gas or air filled microballoons for ultrasonic echography
US5840275A (en) 1990-05-18 1998-11-24 Bracco International B.V. Ultrasonic contrast agent with polymeric gas or air filled microballoons
US5277895A (en) 1990-11-08 1994-01-11 Schering Aktiengesellschaft Mono-n-substituted 1,4,7,10-tetraazacyclododecane derivatives, process for their production and pharmaceutical agents containing these derivatives
US5019371A (en) 1990-11-21 1991-05-28 Mallinckrodt Medical, Inc. Novel x-ray contrast agents, compositions and methods
US5356613A (en) 1991-03-18 1994-10-18 Mallinckrodt Medical, Inc. X-ray contrast agents, compositions and methods
US5529766A (en) 1991-03-28 1996-06-25 Nycomed Imaging As Contrast agents
US5529766C1 (en) 1991-03-28 2002-06-04 Nycomed Imaging As Contrast agents
US5536490A (en) 1991-03-28 1996-07-16 Nycomed Imaging As Contrast agents
US6106806A (en) 1991-03-28 2000-08-22 Nycomed Imaging As Microbubble-containing contrast agents having a non-proteinaceous crosslinked or polymerised amphiphilic shell
US6998107B2 (en) 1991-04-05 2006-02-14 Bristol-Myers Squibb Pharma Comapany Composition comprising low density microspheres
US6528039B2 (en) 1991-04-05 2003-03-04 Bristol-Myers Squibb Medical Imaging, Inc. Low density microspheres and their use as contrast agents for computed tomography and in other applications
US7083778B2 (en) 1991-05-03 2006-08-01 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US5569449A (en) 1991-06-03 1996-10-29 Nycomed Imaging As Gaseous microparticles as ultrasound contrast agents
US5558857A (en) 1991-06-03 1996-09-24 Nycomed Imaging As Contrast agents
US5414114A (en) 1991-07-22 1995-05-09 Bracco International B.V. Method for making conjugate moieties capable of chelating paramagnetic metals and designed for coupling with a factor responsive to specific cellular marker sites
US5573751B1 (en) 1991-09-17 1999-03-09 Sonuc Pharmaceuticals Inc Persistent gaseous bubbles as ultrasound contrast media
US5573751A (en) 1991-09-17 1996-11-12 Sonus Pharmaceuticals, Inc. Persistent gaseous bubbles as ultrasound contrast media
US5614169A (en) 1992-01-09 1997-03-25 Nycomed Imaging As Contrast agents, consisting of galactose particles and an amphilic carboxylic acid
US5567412A (en) 1992-01-09 1996-10-22 Nycomed Imaging As Contrast agents consisting of galactose particles and an amphilic carboxylic acid
US5648062A (en) 1992-01-09 1997-07-15 Nycomed Imaging As Contrast agents consisting of galactose particles
US5558856A (en) 1992-01-09 1996-09-24 Nycomed Imaging As Microbubble-generating contrast agents for ultrasound and magnetic resonance imaging
US5928626A (en) 1992-01-09 1999-07-27 Nycomed Imaging As Contrast agents, consisting of carbohydrate particles
US5637289A (en) 1992-01-09 1997-06-10 Nycomed Imaging As Contrast agents, consisting of galactose particles
US5413774A (en) 1992-01-23 1995-05-09 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US5556610A (en) 1992-01-24 1996-09-17 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
US6187288B1 (en) 1992-02-11 2001-02-13 Bracco International B.V. Stable microbubble suspensions as enhancement agents for ultrasonic echography
US5674468A (en) 1992-03-06 1997-10-07 Nycomed Imaging As Contrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons
US5587199A (en) 1992-08-13 1996-12-24 Bracco International B.V. Process of preparing particles for NMR imaging
US5545395A (en) 1992-08-13 1996-08-13 Bracco Research, S.A. Method of imaging using encapsulated magnetite particles
US5908610A (en) 1992-11-02 1999-06-01 Bracco International B.V. Stable microbubble suspensions comprising saturated phospholipios for ultrasonic echography
US5445813A (en) 1992-11-02 1995-08-29 Bracco International B.V. Stable microbubble suspensions as enhancement agents for ultrasound echography
US5597549A (en) 1992-11-02 1997-01-28 Bracco International B.V. Stable microbubble suspensions as enhancement agents for ultrasound echography
US5686060A (en) 1992-11-02 1997-11-11 Bracco International Bv Stable microbubble suspensions comprising saturated phospholipids for ultrasound echography
US5352436A (en) 1992-11-02 1994-10-04 Drexel University Surfactant-stabilized microbubble mixtures, process for preparing and methods of using the same
US6183725B1 (en) 1992-12-16 2001-02-06 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
US5846518A (en) 1992-12-16 1998-12-08 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media contrast agents containing the media and method
US6506938B1 (en) 1993-07-30 2003-01-14 Bracco International B.V. Process for the purifying of iopamidol
US5958373A (en) 1993-09-07 1999-09-28 Nycomed Salutar Inc. Polychelants as contrast enhancing agents
US6217849B1 (en) 1993-09-29 2001-04-17 Bracco Research S.A. Liposome suspensions as blood pool imaging contrast agents
US6274120B1 (en) 1994-02-15 2001-08-14 Nycomed Imaging As Dry microparticles for use as a contrast agent
US6110444A (en) 1994-03-01 2000-08-29 Nycomed Imaging As Gas-containing microcapsules useful as contrast agents for diagnostic imaging
US5676928A (en) 1994-03-28 1997-10-14 Nycomed Imaging As Liposomes
US5958376A (en) 1994-09-23 1999-09-28 Nycomed Imaging As Iodinated X-ray contrast media
US5958375A (en) 1994-09-23 1999-09-28 Nycomed Imaging As Urea-linked, iodinated bis phenyl compounds for X-ray contrast media
US5882628A (en) 1994-09-23 1999-03-16 Nycomed Imaging As Contrast media
US5993780A (en) 1994-09-23 1999-11-30 Nycomed Imaging As Contrast media
US6310243B1 (en) 1994-09-23 2001-10-30 Nycomed Imaging As Iodinated x-ray contrast media
US5702722A (en) 1994-09-30 1997-12-30 Bracco Research S.A. Liposomes with enhanced entrapment capacity, method and use
US5980937A (en) 1994-09-30 1999-11-09 Bracco Research S.A. Liposomes with enhanced entrapment capacity and their use in imaging
US5856570A (en) 1994-11-29 1999-01-05 Bracco International B.V. Process for preparing 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of the corresponding acid in the presence of a tertiary amine salt or quaternary ammonium salt
US5827504A (en) 1994-12-16 1998-10-27 Bracco Research S.A. Method of echographic imaging using frozen gasbubble suspensions
US5830435A (en) 1994-12-16 1998-11-03 Bracco Research S.A. Method of storing frozen microbubble suspensions
US6521211B1 (en) 1995-06-07 2003-02-18 Bristol-Myers Squibb Medical Imaging, Inc. Methods of imaging and treatment with targeted compositions
US6217850B1 (en) 1995-06-07 2001-04-17 Nycomed Imaging As Method of making lyophilized microbubble compositions useful as contrast agents
US6139819A (en) 1995-06-07 2000-10-31 Imarx Pharmaceutical Corp. Targeted contrast agents for diagnostic and therapeutic use
US5689002A (en) 1995-09-08 1997-11-18 Bracco International B.V. Process for the crystallization from water of (S)-N,N'-bis 2-hydroxy-1-(hydroxymethyl)ethyl!-5- 2-hydroxy-1-oxopropyl)amino!-2,4,6-triiodo-1,3-benzendicarboxamide
US6123920A (en) 1996-01-10 2000-09-26 Nycomed Imaging As Superparamagnetic contrast media coated with starch and polyalkylene oxides
US6165442A (en) 1996-02-19 2000-12-26 Nycomed Imaging As Thermally stabilized ultrasound contrast agent
US6221337B1 (en) 1996-02-19 2001-04-24 Nycomed Imaging As Microbubbles surrounded by a monolayer of negatively charged phospholipids as contrast agents
US7892522B2 (en) 1996-08-02 2011-02-22 Ge Healthcare As Contrast agents
US6165378A (en) 1996-08-30 2000-12-26 Meito Sangyo Kabushiki Kaisha Polysaccharide derivative/magnetic metal oxide composite
US6680047B2 (en) 1996-10-28 2004-01-20 Amersham Health As Diagnostic/therapeutic agents
US6331289B1 (en) 1996-10-28 2001-12-18 Nycomed Imaging As Targeted diagnostic/therapeutic agents having more than one different vectors
US6264917B1 (en) 1996-10-28 2001-07-24 Nycomed Imaging As Targeted ultrasound contrast agents
US7182934B2 (en) 1996-10-28 2007-02-27 Ge Healthcare As Contrast agents
US6051207A (en) 1996-10-28 2000-04-18 Nycomed Imaging As Contrast agents
US6261537B1 (en) 1996-10-28 2001-07-17 Nycomed Imaging As Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors
US6054118A (en) 1997-01-22 2000-04-25 Nycomed Imaging As Contrast agents comprising two types of gas-containing microparticles
US6177061B1 (en) 1997-04-23 2001-01-23 Nycomed Imaging As Contrast agents comprising an azeotropic mixture of two gases for ultrasound investigations
US7413727B2 (en) 1997-04-24 2008-08-19 Ge Healthcare As Contrast agents
US6045777A (en) 1997-06-30 2000-04-04 Acusphere, Inc. Method for enhancing the echogenicity and decreasing the attenuation of microencapsulated gases
US6548047B1 (en) 1997-09-15 2003-04-15 Bristol-Myers Squibb Medical Imaging, Inc. Thermal preactivation of gaseous precursor filled compositions
US6716412B2 (en) 1997-09-15 2004-04-06 Imarx Therapeutics, Inc. Methods of ultrasound treatment using gas or gaseous precursor-filled compositions
US6350908B1 (en) 1998-09-11 2002-02-26 Bracco Imaging S.P.A Process for the preparation of S-N,N′-bis [2-hydroxy-1-(hydroxymethyl) ethyl]-5- [(2-hydroxy-1-oxopropyl) amino]-2,4,6-triiodo-1,3-benzenedicarboxamide
US7374745B2 (en) 1998-10-12 2008-05-20 Mallinckrodt, Inc. Ultrasound contrast agents
US6420603B1 (en) 1998-11-27 2002-07-16 Bracco International B.V. Process for the preparation of n,n'-bis[2,3-dihydroxypropyl]-5-[(hydroxyacetyl) methylamino]-2, 4,6-triiodo-1, 3-benzenedi carboxamide
US7807137B1 (en) 1998-12-22 2010-10-05 University Of Puerto Rico Iron-based contrast agent
US7115778B2 (en) 1999-02-26 2006-10-03 Bracco Imaging, S.P.A. Process for the preparation of iopamidol
US7871597B2 (en) 1999-04-09 2011-01-18 Amag Pharmaceuticals, Inc. Polyol and polyether iron oxide complexes as pharmacological and/or MRI contrast agents
US6406680B1 (en) 1999-09-17 2002-06-18 Nycomed Imaging As X-ray contrast agents
US7745590B1 (en) 2001-11-13 2010-06-29 University Of Utah Research Foundation Degradable macromolecular magnetic resonance imaging contrast agents and methods thereof
US20040019282A1 (en) 2002-07-29 2004-01-29 Mullen Linda J. Hybrid lidar-radar for medical diagnostics
US7368099B2 (en) 2003-02-27 2008-05-06 Kyushu University, National University Corporation MRI contrast agents
US20040249257A1 (en) 2003-06-04 2004-12-09 Tupin Joe Paul Article of manufacture for extracting physiological data using ultra-wideband radar and improved signal processing techniques
US20100234720A1 (en) 2003-06-04 2010-09-16 Tupin Jr Joe Paul System and method for extracting physiological data using ultra-wideband radar and improved signal processing techniques
US7785568B2 (en) 2004-04-21 2010-08-31 Marval Biosciences, Inc. Compositions and methods for enhancing contrast in imaging
US7588751B2 (en) 2004-07-21 2009-09-15 Konica Minolta Medical & Graphic, Inc. Liposome-containing radiographic contrast medium and preparation method thereof
US7592482B2 (en) 2005-09-13 2009-09-22 Bracco Imaging S.P.A. Process for the preparation of contrast agents
US7767196B2 (en) 2005-11-21 2010-08-03 The University Of Hong Kong Optimized relaxivity and specificity hepatobiliary MRI contrast agent
US7485753B2 (en) 2005-12-02 2009-02-03 Ge Healthcare As Contrast agents
US7892520B2 (en) 2006-07-31 2011-02-22 The Hong Kong University Of Science And Technology Solid-state synthesis of iron oxide nanoparticles
US20100322868A1 (en) 2007-07-12 2010-12-23 Mikkel Thaning Contrast agents
US20090192384A1 (en) 2008-01-30 2009-07-30 Siemens Aktiengesellschaft Medical unit and method for improving examination and treatment workflows
WO2010124117A2 (fr) 2009-04-22 2010-10-28 Lifewave, Inc. Dispositif et procédés de contrôle foetal
US20100292559A1 (en) 2009-05-14 2010-11-18 Thilo Hannemann Radar-equipped patient bed for a medical imaging apparatus, and operating method therefor
US7754920B1 (en) 2009-07-21 2010-07-13 Ge Healthcare As Solvent reduction in crystallisation of intermediate for non-ionic X-ray contrast agents

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