KR20020057946A - 다부위 결합을 통해 멀티머 영상제를 표적화하는 방법 - Google Patents
다부위 결합을 통해 멀티머 영상제를 표적화하는 방법 Download PDFInfo
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- KR20020057946A KR20020057946A KR1020027001126A KR20027001126A KR20020057946A KR 20020057946 A KR20020057946 A KR 20020057946A KR 1020027001126 A KR1020027001126 A KR 1020027001126A KR 20027001126 A KR20027001126 A KR 20027001126A KR 20020057946 A KR20020057946 A KR 20020057946A
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Classifications
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- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
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Landscapes
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (5)
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| US14641499P | 1999-07-29 | 1999-07-29 | |
| US16365099P | 1999-11-04 | 1999-11-04 | |
| US60/146,414 | 1999-11-04 | ||
| US60/163,650 | 1999-11-04 | ||
| PCT/US2000/020536 WO2001008712A2 (en) | 1999-07-29 | 2000-07-28 | Targeting multimeric imaging agents through multilocus binding |
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| KR20020057946A true KR20020057946A (ko) | 2002-07-12 |
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| KR1020027001126A Withdrawn KR20020057946A (ko) | 1999-07-29 | 2000-07-28 | 다부위 결합을 통해 멀티머 영상제를 표적화하는 방법 |
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| IL (1) | IL147854A0 (enExample) |
| IS (1) | IS6241A (enExample) |
| MX (1) | MXPA02001017A (enExample) |
| NO (1) | NO20020474L (enExample) |
| NZ (1) | NZ517017A (enExample) |
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| TW319763B (enExample) * | 1995-02-01 | 1997-11-11 | Epix Medical Inc | |
| US6713045B1 (en) | 1995-06-02 | 2004-03-30 | Research Corporation Technologies, Inc. | Targeted magnetic resonance imaging agents for the detection of physiological processes |
| CA2309749A1 (en) | 1997-11-17 | 1999-05-27 | Research Corporation Technologies, Inc. | Magnetic resonance imaging agents for the detection of physiological agents |
| WO2001009188A1 (en) * | 1999-07-29 | 2001-02-08 | Dyax Corp. | Binding moieties for fibrin |
| US6652835B1 (en) * | 1999-07-29 | 2003-11-25 | Epix Medical, Inc. | Targeting multimeric imaging agents through multilocus binding |
| US6673333B1 (en) | 2000-05-04 | 2004-01-06 | Research Corporation Technologies, Inc. | Functional MRI agents for cancer imaging |
| WO2002006287A2 (en) | 2000-07-17 | 2002-01-24 | California Institute Of Technology | Macrocyclic mri contrast agents |
| US6670456B2 (en) * | 2001-02-28 | 2003-12-30 | Dow Global Technologies Inc. | Actinium-225 complexes and conjugates for targeted radiotherapy |
| TWI240632B (en) * | 2001-07-30 | 2005-10-01 | Epix Medical Inc | Purified peptides for peptide-based multimeric targeted contrast agents |
| TWI221406B (en) | 2001-07-30 | 2004-10-01 | Epix Medical Inc | Systems and methods for targeted magnetic resonance imaging of the vascular system |
| JP2005529839A (ja) * | 2001-10-16 | 2005-10-06 | エピックス メディカル， インコーポレイテッド | 脈管内病変の検出および処置 |
| US7504364B2 (en) * | 2002-03-01 | 2009-03-17 | Receptors Llc | Methods of making arrays and artificial receptors |
| DE10231799B4 (de) * | 2002-07-10 | 2006-10-05 | Schering Ag | Verwendung von perfluoralkylhaltigen Metallkomplexen als Kontrastmittel im MR-Imaging zur Darstellung von Intravasalen Thromben |
| US7344704B2 (en) | 2002-07-10 | 2008-03-18 | Schering Ag | Use of perfluoroalkyl-containing metal complexes as contrast media in MR-imaging for visualization of intravascular thrombi |
| US20050136483A1 (en) * | 2003-09-03 | 2005-06-23 | Receptors Llc | Nanodevices employing combinatorial artificial receptors |
| US20040137481A1 (en) * | 2002-09-16 | 2004-07-15 | Receptors Llc | Artificial receptor building blocks, components, and kits |
| US20050037381A1 (en) * | 2002-09-16 | 2005-02-17 | Receptors Llc | Artificial receptors, building blocks, and methods |
| US20060057625A1 (en) * | 2002-09-16 | 2006-03-16 | Carlson Robert E | Scaffold-based artificial receptors and methods |
| US7469076B2 (en) * | 2003-09-03 | 2008-12-23 | Receptors Llc | Sensors employing combinatorial artificial receptors |
| US20060051802A1 (en) * | 2002-09-16 | 2006-03-09 | Receptors Llc | Artificial receptors, building blocks, and methods |
| US20050037429A1 (en) * | 2003-03-28 | 2005-02-17 | Receptors Llc | Artificial receptors including reversibly immobilized building blocks and methods |
| EP1613737A4 (en) * | 2003-03-28 | 2008-12-03 | Receptors Llc | ARTIFICIAL RECEPTORS COMPRISING REVERSIBLE IMMOBILIZED CONSTRUCTION BLOCKS AND METHODS |
| CN1795015A (zh) | 2003-05-23 | 2006-06-28 | 埃匹克斯医药品股份有限公司 | 螯合配位体和造影剂的光学纯和光学富集异构体 |
| DE10325752A1 (de) * | 2003-06-06 | 2004-12-30 | Faustus Forschungs Cie. Translational Cancer Research Gmbh | Lektin-Konjugate |
| AR047692A1 (es) * | 2003-07-10 | 2006-02-08 | Epix Medical Inc | Imagenes de blancos estacionarios |
| CA2445420A1 (en) | 2003-07-29 | 2005-01-29 | Invitrogen Corporation | Kinase and phosphatase assays |
| US7619059B2 (en) | 2003-07-29 | 2009-11-17 | Life Technologies Corporation | Bimolecular optical probes |
| US7557577B2 (en) * | 2003-12-08 | 2009-07-07 | Siemens Aktiengesselschaft | Water-soluble paramagnetic substance reducing the relaxation time of the coolant in an MRI system |
| WO2005079274A2 (en) * | 2004-02-12 | 2005-09-01 | Mount Sinai School Of Medicine | Magnetic resonance imaging of atherosclerotic plaque |
| WO2006028930A2 (en) * | 2004-09-03 | 2006-03-16 | Receptors Llc | Combinatorial artificial receptors including tether building blocks on scaffolds |
| WO2006027244A2 (en) * | 2004-09-10 | 2006-03-16 | Bracco Imaging S.P.A. | Paramagnetic metal polyamino complexes for mri visualization of internalized polynucleotides |
| EP1789792A2 (en) | 2004-09-11 | 2007-05-30 | Receptors LLC | Combinatorial artificial receptors including peptide building blocks |
| WO2006056227A1 (en) * | 2004-11-27 | 2006-06-01 | Eberhard-Karls- Universität Tübingen Universitätsklinikum | Conjugates comprising the active agent and flanking or branched-chain peptides |
| DE102004062258B3 (de) * | 2004-12-23 | 2006-01-05 | Schering Ag | Hydroxypyridinon-Derivate, deren Metallkomplexe und deren Verwendung zur Herstellung von Konjugaten mit Biomolekülen |
| EP1836239B1 (en) | 2005-01-13 | 2008-10-29 | Cinvention Ag | Composite materials containing carbon nanoparticles |
| US20060275217A1 (en) * | 2005-05-06 | 2006-12-07 | Caravan Peter D | Chemical exchange saturation transfer contrast agents |
| CN101222878B (zh) * | 2005-07-13 | 2012-12-26 | 佐治亚州立大学研究基金会 | 显像剂及其制备方法 |
| AU2006303324A1 (en) * | 2005-10-18 | 2007-04-26 | Cinvention Ag | Thermoset particles and methods for production thereof |
| EP1955071A4 (en) | 2005-10-28 | 2009-03-18 | Invitrogen Corp | ASSAYS OF ACTIVITY KINASE AND UBIQUITINATION |
| US20070293656A1 (en) | 2005-12-29 | 2007-12-20 | Epix Pharmaceuticals, Inc. | Collagen binding peptides |
| US20080044358A1 (en) * | 2006-08-17 | 2008-02-21 | Vincent Jacques | Methods for lymph system imaging |
| EP2156186A4 (en) * | 2007-05-03 | 2010-11-03 | Tethys Bioscience Inc | BINDING REAGENTS WITH SMALL EPITOP BINDING MOLECULES |
| DE102007028090A1 (de) | 2007-06-12 | 2008-12-18 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Aktivierbare diagnostische und therapeutische Verbindung |
| WO2009023813A1 (en) * | 2007-08-15 | 2009-02-19 | Applied Soil Water Technologies Llc | Metals recovery from mining heap leach ore |
| US20090214436A1 (en) * | 2008-02-18 | 2009-08-27 | Washington University | Dichromic fluorescent compounds |
| US8722020B2 (en) | 2010-03-31 | 2014-05-13 | General Electric Company | Hydroxylated contrast enhancement agents |
| US8362281B2 (en) | 2010-03-31 | 2013-01-29 | General Electric Company | Intermediates for hydroxylated contrast enhancement agents |
| US8765977B2 (en) | 2010-03-31 | 2014-07-01 | General Electric Company | Hydroxylated contrast enhancement agents and imaging method |
| EP2806781B1 (en) | 2012-01-23 | 2018-03-21 | Washington University | Goggle imaging systems and methods |
| US9849201B2 (en) | 2013-05-03 | 2017-12-26 | Washington University | Homing agents |
| US10806804B2 (en) | 2015-05-06 | 2020-10-20 | Washington University | Compounds having RD targeting motifs and methods of use thereof |
| US10301358B2 (en) | 2015-06-29 | 2019-05-28 | Collagen Medical, LLC | Collagen imaging compositions |
| WO2017027834A1 (en) | 2015-08-13 | 2017-02-16 | The General Hospital Corporation | Manganese-based chelate conjugates for molecular mr imaging |
| EP3576801A4 (en) | 2017-02-02 | 2020-12-16 | The University of Akron | FUNCTIONALIZED POLY (PROPYLENE FUMARATE) POLYMERS MANUFACTURED BY CYCLE OPENING POLYMERIZATION USING MAGNESIUM CATALYSTS |
| EP4072598A4 (en) | 2019-12-13 | 2024-02-21 | Washington University | Near infrared fluorescent dyes, formulations and related methods |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4880008A (en) | 1985-05-08 | 1989-11-14 | The General Hospital Corporation | Vivo enhancement of NMR relaxivity |
| US4777957A (en) * | 1985-06-14 | 1988-10-18 | General Electric Company | Method for measuring and imaging fluid flow |
| EP0247156B1 (en) * | 1985-11-18 | 1993-06-23 | Access Pharmaceuticals Inc. | Polychelating agents for image and spectral enhancement (and spectral shift) |
| DE3786000T3 (de) | 1986-08-18 | 1997-08-21 | Dow Chemical Co | Conjugate dichter Sterne. |
| US5011686A (en) * | 1987-09-21 | 1991-04-30 | Creative Biomolecules, Inc. | Thrombus specific conjugates |
| GB8808305D0 (en) * | 1988-04-08 | 1988-05-11 | Nycomed As | Compositions |
| US5914095A (en) | 1989-04-07 | 1999-06-22 | Salutar, Inc. | Polychelants containg amide bonds |
| ATE166864T1 (de) | 1989-10-23 | 1998-06-15 | Nycomed Salutar Inc | Mehrzähnige metall-chelatierende verbindungen |
| GB9320277D0 (en) | 1993-10-01 | 1993-11-17 | Nycomed Salutar Inc | Chelants |
| US5650133A (en) * | 1990-01-19 | 1997-07-22 | Nycomed Salutar | Macrocyclic polyaza dichelates linked through ring nitrogens via an amide or ester functionality |
| US5631329A (en) | 1990-08-27 | 1997-05-20 | Dendritech, Inc. | Process for producing hyper-comb-branched polymers |
| WO1992021017A1 (en) * | 1991-05-23 | 1992-11-26 | Unger Evan C | Liposoluble compounds for magnetic resonance imaging |
| JP2894879B2 (ja) * | 1991-10-04 | 1999-05-24 | 日本メジフィジックス株式会社 | 診断用造影剤 |
| US5522390A (en) * | 1991-11-21 | 1996-06-04 | U.S. Philips Corporation | Magnetic resonance imaging method |
| US5637759A (en) | 1992-07-30 | 1997-06-10 | The Regents Of The University Of California | Metal-ligating amino acid derivatives for MRI and for peptide synthesis |
| DE69332203T2 (de) | 1992-10-02 | 2003-05-28 | Diatide, Inc. | Multimerische mehrzweckwirkstoffe gegen thrombose |
| US5726304A (en) | 1992-10-30 | 1998-03-10 | The University Of British Columbia | Porphocyanine and CNC-expanded porphyrins |
| US5401493A (en) * | 1993-03-26 | 1995-03-28 | Molecular Biosystems, Inc. | Perfluoro-1H,-1H-neopentyl containing contrast agents and method to use same |
| US5579767A (en) * | 1993-06-07 | 1996-12-03 | Prince; Martin R. | Method for imaging abdominal aorta and aortic aneurysms |
| GB9314499D0 (en) * | 1993-07-12 | 1993-08-25 | Nycomed Imaging As | Method |
| GB9318550D0 (en) | 1993-09-07 | 1993-10-20 | Nycomed Salutar Inc | Chelants |
| DE4344460A1 (de) * | 1993-12-22 | 1995-06-29 | Schering Ag | Metallkomplexe von dendrimeren Makromolekülen, diese enthaltende diagnostische Mittel sowie Verfahren zur Herstellung der Komplexe und Mittel |
| IT1270994B (it) | 1994-03-18 | 1997-05-26 | Bracco Spa | Macromolecole ramificate a struttura poliossialchilica e loro usi |
| WO1995027705A1 (en) | 1994-04-08 | 1995-10-19 | Bracco International B.V. | Aromatic amide compounds and metal chelates thereof |
| GB9407812D0 (en) | 1994-04-20 | 1994-06-15 | Nycomed Salutar Inc | Compounds |
| DE4425857A1 (de) * | 1994-07-07 | 1996-01-11 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zur ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
| WO1998053855A1 (en) * | 1997-05-30 | 1998-12-03 | Alliance Pharmaceutical Corp. | Methods and apparatus for monitoring and quantifying the movement of fluid |
| US6232295B1 (en) | 1994-10-12 | 2001-05-15 | Jon Faiz Kayyem | Cell-specific contrast agent and gene delivery vehicles |
| TW319763B (enExample) * | 1995-02-01 | 1997-11-11 | Epix Medical Inc | |
| DE19518222A1 (de) | 1995-05-11 | 1996-11-14 | Schering Ag | Verwendung von polymeren Kontrastmittel mittleren Molekulargewichts zur Differenzierung von benignen und malignen Tumoren mittels moderner bildgebender Verfahren |
| DE19521945A1 (de) | 1995-06-12 | 1996-12-19 | Schering Ag | Kaskadenpolymere mit Iodaromaten |
| DE19525924A1 (de) * | 1995-07-04 | 1997-01-09 | Schering Ag | Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
| US5919442A (en) | 1995-08-11 | 1999-07-06 | Dendritech, Inc. | Hyper comb-branched polymer conjugates |
| IT1277596B1 (it) | 1995-09-15 | 1997-11-11 | Bracco Spa | Composti macromolecolari di tipo dendrimerico |
| US6638508B2 (en) * | 1995-12-21 | 2003-10-28 | Yeda Research And Development Co., Ltd. | Modified avidin-type molecules as targeting agents for the liver and cells of the reticuloendothelial system |
| IT1283218B1 (it) * | 1996-03-08 | 1998-04-16 | Bracco Spa | Polichelanti, loro complessi con ioni metallici, loro preparazione e loro usi |
| PT907379E (pt) | 1996-04-01 | 2004-09-30 | Epix Medical Inc | Agentes de contraste bioactivados para imagiologia de diagnostico |
| WO1997041856A1 (en) | 1996-05-08 | 1997-11-13 | Massachusetts Institute Of Technology | ORGANOMETALLIC LIGANDS FOR THE LOCALIZATION AND QUANTIFICATION OF AMYLOID IN VIVO AND $i(IN VITRO) |
| DE19641197C2 (de) * | 1996-09-24 | 1999-02-18 | Schering Ag | Ionenpaare und ihre Verwendung als Kontrastmittel |
| NZ500273A (en) * | 1997-03-18 | 2001-12-21 | Nihon Schering Kabushiki Kaish | Gadolinium (Gd) polymer MRI contrast agent responsive to environmental changes |
| DE19731300C1 (de) * | 1997-07-11 | 1999-01-21 | Schering Ag | Perfluoralkylgruppenhaltige Trijodaromaten, Verfahren zu deren Herstellung und deren Verwendung als Kontrastmittel |
| US6073042A (en) * | 1997-09-25 | 2000-06-06 | Siemens Medical Systems, Inc. | Display of three-dimensional MRA images in which arteries can be distinguished from veins |
| CA2309749A1 (en) * | 1997-11-17 | 1999-05-27 | Research Corporation Technologies, Inc. | Magnetic resonance imaging agents for the detection of physiological agents |
| US6858210B1 (en) | 1998-06-09 | 2005-02-22 | La Jolla Pharmaceutical Co. | Therapeutic and diagnostic domain 1 β2GPI polypeptides and methods of using same |
| US6112112A (en) * | 1998-09-18 | 2000-08-29 | Arch Development Corporation | Method and system for the assessment of tumor extent in magnetic resonance images |
| US6342598B1 (en) * | 1998-11-26 | 2002-01-29 | Bracco International B.V. | Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents |
| US6458953B1 (en) * | 1998-12-09 | 2002-10-01 | La Jolla Pharmaceutical Company | Valency platform molecules comprising carbamate linkages |
| US6399578B1 (en) * | 1998-12-09 | 2002-06-04 | La Jolla Pharmaceutical Company | Conjugates comprising galactose α1,3 galactosyl epitopes and methods of using same |
| WO2001009188A1 (en) * | 1999-07-29 | 2001-02-08 | Dyax Corp. | Binding moieties for fibrin |
| US6652835B1 (en) * | 1999-07-29 | 2003-11-25 | Epix Medical, Inc. | Targeting multimeric imaging agents through multilocus binding |
| EP1379885A4 (en) * | 2001-01-05 | 2005-07-06 | Univ Duke | CONTRAST REINFORCING AGENT FOR MAGNETIC RESONANCE IMAGING |
| US6459264B1 (en) * | 2001-02-22 | 2002-10-01 | Mayo Foundation For Medical Education And Research | Real-time embedded magnetic resonance fluoroscopy |
| JP2005534697A (ja) * | 2002-08-06 | 2005-11-17 | エピックス ファーマシューティカルズ， インコーポレイテッド | ペプチド凝集体 |
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| EA200200220A1 (ru) | 2002-08-29 |
| CZ2002343A3 (cs) | 2002-08-14 |
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| WO2001008712A3 (en) | 2002-03-14 |
| MXPA02001017A (es) | 2002-08-12 |
| JP2003201258A (ja) | 2003-07-18 |
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| NZ517017A (en) | 2004-05-28 |
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