Technetium Containing (at. No. 43; Tc) Patents (Class 534/14)
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Patent number: 5618513Abstract: A method for radiolabelling peptides using polyaminocarboxylate ligands having suitable protecting groups such that they can be added to peptides by standard solid phase or solution phase peptide synthetic chemistry and can be deproteced using standard cleavage/deprotection reagents and produce the peptide/chelate conjugate as a high purity mono-addition product is provided. The cleaved and deprotected ligand-peptide molecules can then be labeled with lanthanide or actinide radionuclides. The protected polyaminocarboxylate ligands form mono-anhydrides or mono-active esters under solid phase or solution phase conditions and permit only the desired monoaddition chelate-peptide conjugate to be formed.Type: GrantFiled: June 7, 1995Date of Patent: April 8, 1997Assignee: Mallinckrodt Medical, Inc.Inventor: Ananthachari Srinivasan
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Patent number: 5608110Abstract: Novel compounds containing a heteroatom-bearing bridge and novel complexes of these compounds with metals. The novel compounds and complexes are useful in diagnostic and therapeutic methods.Type: GrantFiled: May 18, 1994Date of Patent: March 4, 1997Assignee: Bracco International B.V.Inventors: Kondareddiar Ramalingam, Natarajan Raju
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Patent number: 5602236Abstract: Metal-containing steroid mimic complexes are provided. Compositions containing a metal ion incorporated into a steroid skeleton structure and ligands useful in the preparation of such compositions are also provided. The metal ion is preferably a radionuclide, such as technetium, rhenium or gallium. Methods for using the metal complexes for diagnostic and therapeutic purposes are further provided.Type: GrantFiled: April 8, 1994Date of Patent: February 11, 1997Assignee: Mallinckrodt Medical, Inc.Inventor: Raghavan Rajagopalan
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Patent number: 5602267Abstract: Asymmetric synthesis using a novel catalyst comprising the formula: ##STR1## and which has utility in areas such as epoxidation of olefins.Type: GrantFiled: May 26, 1995Date of Patent: February 11, 1997Assignee: Hoechst CelaneseInventor: Shu-Hai Zhao
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Patent number: 5601800Abstract: A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.Type: GrantFiled: July 29, 1994Date of Patent: February 11, 1997Assignee: Curators of the University of MissouriInventors: Kattesh V. Katti, Wynn A. Volkert, Alan R. Ketring, Prahlad R. Singh
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Patent number: 5593656Abstract: This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer.gtoreq.Type: GrantFiled: June 7, 1995Date of Patent: January 14, 1997Assignee: Cytogen CorporationInventors: Benjamin A. Belinka, Jr., Daniel J. Coughlin, Vernon L. Alvarez, Richard Wood
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Patent number: 5589576Abstract: Novel complexes of technetium (.sup.99 Tc or .sup.99m Tc) which contain the moiety Tc.dbd.NR, Tc--N.dbd.NY or Tc(--N.dbd.NY).sub.2, and a ligand which confers biological target-seeking properties on the complex, wherein R represents an aryl group, a substituted or unsubstituted alkyl group, or the grouping .dbd.NR.sup.1 R.sup.2 ; Y represents an aryl group or a substituted or unsubstituted alkyl group; and R.sup.1 and R.sup.2 are hydrogen, aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and may be both the same or different, provided that both are not hydrogen. The complexes are suitable for use in radiopharmaceuticals for a variety of clinical applications. Methods for the preparation of these technetium complexes are also described.Type: GrantFiled: August 12, 1994Date of Patent: December 31, 1996Assignee: Amersham International plcInventors: Colin M. Archer, Jonathan R. Dilworth, Panna Jobanputra, Ian A. Latham, Russell M. Thompson
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Patent number: 5587394Abstract: Families of Diels Alder adducts and of metal complexes of Diels Alder adducts, which are useful as particularly active compounds for use in photodynamic therapy, are disclosed. The Diels Alder adducts and a preferred family of metal complexes have the structures of Formulas 1, 2, 3 and 4, below: ##STR1## where R1, R2, R3 and R4 can be the same or different, and each is methyl, ethyl or an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carbonyl function of the adduct, R5, R6 and R7 can be the same or different, and each is ethyl or an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carbonyl function of the adduct.Type: GrantFiled: June 7, 1995Date of Patent: December 24, 1996Assignees: The University of Toledo, Medical College of OhioInventors: Alan R. Morgan, Steven H. Selman
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Patent number: 5585468Abstract: This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, substantial thioureas for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.Type: GrantFiled: June 27, 1994Date of Patent: December 17, 1996Assignee: Cytogen CorporationInventors: Daniel J. Coughlin, Benjamin A. Belinka, Jr.
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Patent number: 5578288Abstract: This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'-- NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer.gtoreq.Type: GrantFiled: June 7, 1995Date of Patent: November 26, 1996Assignee: Cytogen CorporationInventors: Benjamin A. Belinka, Jr., Daniel J. Coughlin, Vernon L. Alvarez, Richard Wood
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Patent number: 5574140Abstract: Radionuclide chelating compounds are provided for conjugation to targetting molecules such as proteins, peptides or antibodies. The resulting labelled targetting molecules may be used in diagnosis and therapy.Type: GrantFiled: July 14, 1994Date of Patent: November 12, 1996Assignee: Resolution Pharmaceutical Inc.Inventors: Alfred Pollack, Robert A. Kirby, Robert Dufault
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Patent number: 5567408Abstract: Peptides containing a biological-function domain which includes the sequence Tyr-Ile-Gly-Ser-Arg (YIGSR) and a medically useful metal ion-binding domain are labeled with medically useful metal ions for use in a variety of diseases and pathologic conditions, and particularly for diagnosis and treatment of thrombosis and other diseases and conditions.Type: GrantFiled: June 6, 1995Date of Patent: October 22, 1996Assignee: RhoMed IncorporatedInventor: Paul O. Zamora
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Patent number: 5563262Abstract: Families of Diels Alder adducts and of metal complexes of Diels Alder adducts, which are useful as particularly active compounds for use in photodynamic therapy, are disclosed. The Diels Alder adducts and a preferred family of metal complexes have the structures of Formulas 1, 2, 3 and 4, below: ##STR1## where R1, R2, R3 and R4 can be the same or different, and each is methyl, ethyl or an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carbonyl function of the adduct, R5, R6 and R7 can be the same or different, and each is ethyl or an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carbonyl function of the adduct, M comprises a metal cation, e.g., Sn or Zn, that is complexed with two of the nitrogens of the adduct, and R8 is an alkyl group other than t-butyl having from one to four carbon atoms.Type: GrantFiled: October 11, 1994Date of Patent: October 8, 1996Assignees: University of Toledo, Medical College of OhioInventors: Alan R. Morgan, Steven H. Selman
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Patent number: 5561220Abstract: This invention relates to compositions that are radiolabeled scintigraphic imaging agents, comprising a polybasic compound covalently linked to a radiolabel binding moiety and the composition further comprising a polysulfated glycan. The invention also provides methods for producing and using such compositions. Specifically, the invention relates to compositions comprised of technetium-99m (Tc-99m) labeled scintigraphic imaging agents comprising a polybasic compound having at least 5 chemical functionalities that are basic at physiological pH and a radiolabel-binding moiety, the composition further comprising a polysulfated glycan, the composition being capable of specifically binding to inflammatory sites in vivo. Methods and kits for making such compositions, and methods for using such compositions to image sites of infection and inflammation in a mammalian body, are also provided.Type: GrantFiled: June 7, 1993Date of Patent: October 1, 1996Assignee: Diatech, Inc.Inventors: Richard T. Dean, Brian R. Moyer
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Patent number: 5559214Type: GrantFiled: May 28, 1993Date of Patent: September 24, 1996Assignee: Sterling Winthrop Inc.Inventors: Daniel J. Delecki, Ashis K. Saha, Robert A. Snow
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Patent number: 5556982Abstract: Protein, ligand and anti-ligand conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the compositions efficiently.Type: GrantFiled: July 12, 1993Date of Patent: September 17, 1996Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Linda M. Gustavson
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Patent number: 5556609Abstract: Peptides containing a biological-function domain which includes the sequence Tyr-Ile-Gly-Ser-Arg (YIGSR) SEQ. ID No. 1) and a medically useful metal ion-binding domain are labeled with medically useful metal ions for use in a variety of diseases and pathologic conditions, and particularly for diagnosis and treatment of thrombosis and other diseases and conditions.Type: GrantFiled: December 30, 1992Date of Patent: September 17, 1996Assignee: RhoMed IncorporatedInventor: Paul O. Zamora
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Patent number: 5556939Abstract: Technetium or rhenium radionuclide labelled chelate-hexapeptide complexes are useful for the selective detection or treatment of tumors with somatostatin receptors. In particular, compounds of formula: ##STR1## (wherein R, R.sup.1, R.sup.3 and A are as defined herein) incorporating an N3S2 chelate may be labelled with a radionuclide. The resulting complexes are useful as radioimaging agents or as radiopharmaceuticals for the treatment of certain tumors.Type: GrantFiled: October 13, 1994Date of Patent: September 17, 1996Assignee: Merck Frosst Canada, Inc.Inventors: Richard J. Flanagan, Jean-Marc Dufour, Keith T. Hogan
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Patent number: 5554749Abstract: The present invention provides new and structurally diverse compositions comprising compounds of the general formula: ##STR1## Wherein U is --(CH.sub.2).sub.n X or --(CH.sub.2).sub.n NR.sub.1 (CH.sub.2)X; R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl or C.sub.1 -C.sub.8 alkoxyalkyl; V is --(CH.sub.2).sub.n X, --(CH.sub.2).sub.n NR.sub.1 (CH.sub.2)X, hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl or C.sub.1 -C.sub.8 alkoxyalkyl; V and R.sub.1 may jointly be --(CH.sub.2).sub.m -- to form a heterocyclic ring; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH; a, b, c, d, n and m may be the same or different and are from one to about ten, preferably from one to about three.Methods for imaging using compositions of the invention are also provided.Type: GrantFiled: January 14, 1994Date of Patent: September 10, 1996Assignee: Mallinckrodt Medical, Inc.Inventors: Rebacca A. Wallace, Dennis A. Moore
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Patent number: 5538712Abstract: The invention relates to cyctopentadienylcarbonyl.sup.99m Tc complexes of general formula I ##STR1## in which --XR can have various meanings. These new complexes of .sup.99m technetium can be used in the field of medical diagnosis. The invention further relates to a process for the production of complexes according to the invention.Type: GrantFiled: January 29, 1993Date of Patent: July 23, 1996Assignee: Institut Fur Diagnostikforschung GmbH/an der Freien Universitat BerlinInventors: Martin Wenzel, Paul E. Schulze
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Patent number: 5534497Abstract: The invention relates to a technetium chelate of the general formula ##STR1## wherein X is a sulphur atom or an imino group,Z is a hydrogen atom, a carboxy group, an alkoxycarbonyl group having 1-4 carbon atoms, an aminocarbonyl group, a sulpho group, an aminosulphonyl group or a carboxymethylaminocarbonyl group,Tc represents technetium-99 m,R.sub.1 is a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, andR.sub.2, R.sub.3, R.sub.4 and R.sub.5 are equal or different and represent hydrogen, atoms or branched or non-branched alkyl groups having 1-4 carbon atoms, which alkyl groups are optionally substituted with an amino group, a hydroxy group, a mercapto group, a halogen atom, a carboxy group or an aminocarbonyl group,with the proviso that R.sub.3, R.sub.4 and R.sub.5 do not all three of them represent hydrogen atoms; as well as water-soluble salts of these compounds.Type: GrantFiled: June 4, 1993Date of Patent: July 9, 1996Assignee: Mallinckrodt Medical, Inc.Inventor: Alfons M. Verbruggen
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Patent number: 5531978Abstract: There are provided chelating agents particularly useful for the preparation of diagnostic and therapeutic agents for magnetic resonance imaging, scintigraphy, ultrasound imaging, radiotherapy and heavy metal detoxification, said agents being compounds of formula IX--CHR.sub.1 --NZ--(CHR.sub.1).sub.n --A--(CHR.sub.1).sub.m --NZ--CHR.sub.1 --X (I)wherein n and m are 2, 3 or 4; and A, X, R.sub.1 and Z are as defined in the specification.Type: GrantFiled: February 8, 1993Date of Patent: July 2, 1996Assignee: Nycomed Imaging ASInventors: Arne Berg, Torsten Almen, Jo Klaveness, Pal Rongved, Terje Thomassen, Harald Dugstad
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Patent number: 5527885Abstract: This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.Type: GrantFiled: June 30, 1994Date of Patent: June 18, 1996Assignee: Cytogen CorporationInventors: Daniel J. Coughlin, Benjamin A. Belinka, Jr.
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Patent number: 5508458Abstract: A novel catalyst comprising the formula: ##STR1## and which has utility in areas such as epoxidation of olefins.Type: GrantFiled: May 26, 1995Date of Patent: April 16, 1996Assignee: Hoechst Celanese CorporationInventor: Shu-Hai Zhao
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Patent number: 5506345Abstract: Agents for the diagnosis or treatment of hypoxic cells comprise a bioreductive moiety such as 2-nitroimidazole, and a metal chelating moiety which is a bis-amine oxime of which a carbon atom adjacent a nitrogen atom is linked to the bioreductive moiety. A chelated metal atom or ion preferably Technetium-99m. The agent diffuses into cells where the 2-nitroimidazole is reduced thus trapping the chelated metal in the cell.Type: GrantFiled: July 25, 1994Date of Patent: April 9, 1996Assignee: Amersham International plcInventors: Anthony L. Riley, James D. Kelly
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Patent number: 5496929Abstract: The invention concerns a radiopharmaceutical product having in particular a cerebral tropism comprising a nitruro complex of a transition metal and the method for preparing said product. This complex satisfies the formula (M.tbd.N)L.sup.1 L.sup.2 (I) in which M is a transition metal, such as Tc99m, Re 186 or Re188, and L.sup.1 and L.sup.2, which may be identical or different, satisfy the formula ##STR1## in which R.sup.1 and R.sup.2 may be alkyl radicals, V and W may be O, S or Se, n=0 or 1, l=0 or 1, m=0 or 1, and X represents N--C, C, or As.Type: GrantFiled: May 19, 1994Date of Patent: March 5, 1996Assignee: Cis Bio InternationalInventors: Roberto Pasqualini, Emmanuel Bellande, Ve/ ronique Comazzi, Jacques Laine/
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Patent number: 5459159Abstract: Pyropheophorbide compounds are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compounds are exposed to a particular wavelength of light the compounds become cytotoxic and destroy the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have shown improved results as compared to drugs currently used in photodynamic therapy. Further, they absorb light further in the red, optimizing tissue penetration and are retained in the skin for short time periods relative to other drugs used in photodynamic therapy.Type: GrantFiled: May 5, 1994Date of Patent: October 17, 1995Assignee: Health Research, Inc.Inventors: Ravindra K. Pandey, Thomas J. Dougherty
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Patent number: 5449761Abstract: This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R' and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer .gtoreq.2, provided that the groups R, R', R', L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer .gtoreq.Type: GrantFiled: September 28, 1993Date of Patent: September 12, 1995Assignee: Cytogen CorporationInventors: Benjamin A. Belinka, Jr., Daniel J. Coughlin, Vernon L. Alvarez, Richard Wood
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Patent number: 5431900Abstract: Radiopharmaceuticals consisting essentially of a lipophilic, charge neutral radionuclide complex of a diaminedithiol ligand having 1-4 ester groups of the formula --A--COOR where A is a straight or branched chain alkylene of 0-10 carbon atoms and R is an alkyl group of 1-10 carbon atoms are useful in radioimaging brain perfusion in primates. Ester-substituted diaminedithiols in sterile, pharmaceutically acceptable form, and kits of the diaminedithiols and sterile, non-pyrogenic reducing agents for reducing preselected radionuclides are also provided. Technetium-99m is a preferred radionuclide.Type: GrantFiled: October 20, 1993Date of Patent: July 11, 1995Assignee: The Du Pont Merck Pharmaceutical CompanyInventors: Paul L. Bergstein, Edward H. Cheesman, Alan D. Watson
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Patent number: 5428154Abstract: The invention is a chelate of formula I: ##STR1## wherein R.sub.1-4 is --CH.sub.2 COOH;n is 1 to 5;X is a member selected from the group consisting of--NO.sub.2,--NH.sub.2,--NCS,--NHCOCH.sub.2 --Z, with Z being a member selected from the group consisting of Br and I,--COOH; and--OCH.sub.2 OOCH;and M is a metal ion selected from the group of elements consisting ofBi, Pb, Y, Cd, Hg, Al, Th, Sr, and Lanthanides.The invention also includes a chelate, wherein M is a copper ion and n is an integer from 2 to 5. The invention includes chelate conjugates of formula I and ligand conjugates of formula II: ##STR2## The invention also includes methods to use these compounds for treatment of cellular disorders and for diagnostic tests.Type: GrantFiled: October 22, 1993Date of Patent: June 27, 1995Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Otto A. Gansow, Martin W. Brechbiel, Michael A. Magerstadt
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Patent number: 5428139Abstract: Complexes of bicyclopolyazamacrocyclophosphonic acid compounds with a metal ion, e.g. .sup.153 Sm, .sup.177 Lu, .sup.159 Gd, .sup.149 Pm, .sup.140 La, .sup.175 Yb, .sup.166 Ho, .sup.90 Y, .sup.47 Sc, .sup.186 Re, .sup.188 Re, .sup.142 Pr, .sup.99m Tc, .sup.67 Ga, .sup.68 Ga, .sup.105 Rh, .sup.97 Ru, .sup.111 In, .sup.113m In or .sup.115m In ion, are disclosed. The complexes can be covalently attached to a biologically active molecule, e.g. an antibody or antibody fragment, to form conjugates. The complexes and conjugates are useful as radiopharmaceutical agents for therapy and/or diagnostic purposes.Type: GrantFiled: December 10, 1991Date of Patent: June 27, 1995Assignee: The Dow Chemical CompanyInventors: Garry E. Kiefer, Jaime Simon
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Patent number: 5425935Abstract: A 4-quinolone antibiotic compound is used in gamma ray scintigraphy diagnostic imaging of a patient with a metallic radionuclide so as to locate focal infection.Type: GrantFiled: May 12, 1993Date of Patent: June 20, 1995Assignee: British Technology Group LimitedInventor: Kishor K. Solanki
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Patent number: 5422095Abstract: There is disclosed an imaging agent for diagnosis comprising a compound composed of a polynuclear type compound of the formula I or II: ##STR1## wherein each X is a hydrogen atom or a bifunctional ligand, at least one of them are bifunctional ligand and m or n is an integer of 1 to 6, and at least one metal ion being coordinated with at least one bifunctional ligand moiety, said metal ion being selected from the group consisting of metal ions having the atomic number of 21-29, 31, 32, 37-39, 42-44, 49 and 56-83.Type: GrantFiled: April 4, 1994Date of Patent: June 6, 1995Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Yuji Hashiguchi, Kumiko Iwai, Shigemi Seri, Susumu Kondo, Makoto Azuma
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Patent number: 5420321Abstract: Tris(isonitrile)copper(I) sulfate complexes and their use in synthetic methods for making radionuclide isonitrile coordination complexes such as [.sup.99m Tc(1-isocyano-2-methoxy-2-methylpropane).sub.6 ].sup.+. The coordination complexes are useful as radiopharmaceutical imaging agents.Type: GrantFiled: August 3, 1993Date of Patent: May 30, 1995Assignee: The Du Pont Merck Pharmaceutical CompanyInventor: David S. Edwards
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Patent number: 5399339Abstract: Process for the preparation of nitride complexes of transition metals for use as radiopharmaceutical products or for the synthesis of novel pharmaceutical products. The process consists in reacting an oxygenic transition metal compound such as 99m.sub.Tc, 186.sub.Re or 188.sub.Re, with a first nitrogenous ligand such as sodium nitride or a nitrogenous compound such as S-methyl, N-methyl dithiocarbazate, and a reducing agent consisting of either tin (II) or a dithionite. The product so obtained can be used for the preparation of radiopharmaceutical products by a reaction with a second ligand such as sodium dithiocarbamate.Type: GrantFiled: January 21, 1993Date of Patent: March 21, 1995Assignee: CIS BIO InternationalInventors: Roberto Pasqualini, Veronique Comazzi, Emmanuel Bellande
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Patent number: 5395608Abstract: A group of functionalized triamine chelants and their derivatives that form complexes with radioactive metal ions are disclosed. The complexes can be covalently attached to a protein or an antibody or antibody fragment and used for therapeutic and/or diagnostic purposes. The chelants are of the formula: ##STR1## wherein n, m, R, R.sup.1, R.sup.2 and L are defined in the specification.Type: GrantFiled: May 9, 1991Date of Patent: March 7, 1995Assignee: The Curators of the University of MissouriInventors: David E. Troutner, Christy S. John, Maroor R. A. Pillai
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Patent number: 5387409Abstract: Boronic acid adducts of technetium-99m and radioactive rhenium dioxime complexes, each of which include biochemically active groups, are useful as diagnostic and therapeutic agents, respectively.Type: GrantFiled: January 7, 1992Date of Patent: February 7, 1995Assignee: Bracco International B.V.Inventors: Adrian D. Nunn, Karen E. Linder, Silvia Jurisson, William C. Eckelman
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Patent number: 5382654Abstract: A diagnostic composition suitable for administration to a warm-blooded animal comprising somatostatin or a molecule capable of interacting with the somatostatin receptor labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of tumors or therapeutic effects on tumors.Type: GrantFiled: February 5, 1992Date of Patent: January 17, 1995Assignee: Mallinckrodt Medical, Inc.Inventors: Leon R. Lyle, Raghavan Rajagopalan, Karen Deutsch
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Patent number: 5374416Abstract: The invention relates to ligands of formula ##STR1## in which B represents an ##STR2## W representing the ##STR3## group, in which groups X and Z represent a heterocycle. The invention also relates to the monometallic or polymetallic complexes formed by these ligands with metal ions chosen from lanthanide ions, transition metal ions. barium, bismuth, lead and the radioisotopes .sup.99m Tc, .sup.111 In, .sup.90 Y, .sup.64 Cu and .sup.169 Yb, as well as the physiologically acceptable salts of these complexes.The salts of these complexes may be used as diagnostic or therapeutic agents in nuclear magnetic resonance imaging and X-ray radiology, as in-vivo chemical shift agents and in nuclear medicine.Type: GrantFiled: November 17, 1992Date of Patent: December 20, 1994Assignee: Guerbet S.A.Inventors: Olivier Rousseaux, Michel Schaefer, Anne Bouillot, Dominique Meyer
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Patent number: 5371184Abstract: A diagnostic composition suitable for administration to a warm-blooded animal comprising hirudin or a molecule capable of interacting with the hirudin receptor labeled with a radionuclide by means of a chelate ligand capable of administration to an animal to produce reliable visual imaging of thrombus.Type: GrantFiled: February 5, 1992Date of Patent: December 6, 1994Assignee: Mallinckrodt Medical, Inc.Inventors: Raghavan Rajagopalan, Leon R. Lyle, Thomas J. Dunn
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Patent number: 5358712Abstract: Novel anticholinergics which are related to vesamicol are particularly useful when radiolabeled for evaluating cholinergic innervation in the living human brain. The cholinergic deficit in the Alzheimer's brain should be identifiable with these radioligands.Type: GrantFiled: September 8, 1993Date of Patent: October 25, 1994Assignee: Regents of the University of MinnesotaInventors: Simon M. Efange, Stanley M. Parsons
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Patent number: 5350837Abstract: The ligand L, (R.sup.3)(R.sup.4)(R.sup.5)C--N(R)--C(R.sup.1)(R.sup.2)--(CH.sub.2).sub.n --COOH L where R is hydrogen, hydroxy, alkyl, hydroxyalkyl, or alkylcarboxy, or R and R.sup.1 together may form a mono-, di-, tri-, or tetra-methylene radical, or R and R.sup.3 together may form a mono-, di-, tri-, or tetra-methylene radical, and R.sup.1 and R.sub.2 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy, alkylcarboxy, alkylamine, alkylthiol, aryl or R.sup.1 and R.sup.2 together may form a tetra- or penta-methylene radical, and R.sup.3 and R.sup.4 and R.sup.5 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy, alkylcarboxy, provided that at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxyalkyl, and n is equal to 0, 1 or 2, for example tricine, form useful complexes with .sup.99m Tc, for radiolabelling macromolecules such as monoclonal antibodies.Type: GrantFiled: May 3, 1993Date of Patent: September 27, 1994Assignee: Johnson Matthey Public Limited CompanyInventors: Gary J. Bridger, Pedro E. Hernandez, John D. Higgins, III, Scott K. Larsen
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Patent number: 5346995Abstract: A new method for synthesizing 2-alkoxyisobutylisonitrile is provided in which isobutylene is used as the starting material. The haloalkoxylation of isobutylene in alcohol medium gives 2-alkoxyisobutylhalide which is then converted to 2-alkoxyisobutylamine. In the basic condition, the reaction of 2-alkoxyisobutylamine with chloroform produces 2-alkoxyisobutylisonitrile. The synthesis process contains three steps by which a higher yield is achieved. 2-Alkoxyisobutylisonitrile is labelled with technetium-99m by exchange labelling of stable tetrakis(2-alkoxyisobutylisonitrile)copper(I) complex. Tetrakis(2-alkoxyisobutylisonitrile)copper(I) complex can be prepared by the exchange of acetonitrile molecules in tetrakis(acetonitrile)copper(I) complex with isonitrile ligands.Type: GrantFiled: January 13, 1993Date of Patent: September 13, 1994Assignee: Institute of Nuclear Energy ResearchInventors: Lee Te-Wei, Ting Gann, Su Chang-Shinn, Chyi Shyh-Yi
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Patent number: 5342926Abstract: Analogs of cytochalasin B are used as radiopharmaceuticals to provide an image for the nuclear imaging of glucose transport across cell membranes. Like cytochalasin B, the analogs bind specifically to glucose transport protein, and in doing so, serve as markers indicating the amount of glucose transport protein present on the surfaces of cells. The analogs differ from cytochalasin B by the inclusion of a radionuclide in the region of the terminal phenyl group on cytochalasin B, where the radionuclide does not interfere with the binding specificity of the analog. Disclosed herein are such analogs as well as analogs with which readily accept radionuclides at the desired location on the structure, either by conjugation or substitution.Type: GrantFiled: June 8, 1993Date of Patent: August 30, 1994Assignee: The Regents of the University of CaliforniaInventor: Robert S. Hattner
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Patent number: 5336482Abstract: Disclosed are cationic complexes of Tc-99m and ligands having the structure: ##STR1## wherein: R.sup.1 is hydrogen or is selected from the group consisting of C.sub.1 to C.sub.20 alkyl; C.sub.3 to C.sub.12 cycloalkyl; C.sub.7 to C.sub.24 aralkyl; C.sub.2 to C.sub.16 alkyl ethers, thioethers, ketones or esters; C.sub.7 to C.sub.27 aralkyl ethers;R.sup.2 is hydrogen or is a C.sub.1 to C.sub.4 lower alkyl radical selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl.Type: GrantFiled: December 5, 1991Date of Patent: August 9, 1994Assignee: The Du Pont Merck Pharmaceutical CompanyInventors: David S. Edwards, Christopher E. R. Orvig, Michael J. Poirier
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Patent number: 5330738Abstract: The present invention relates to novel technetium-99m complexes and to methods of preparing the complexes. The present invention further relates to a radiopharmaceutical compositions comprising the complexes, to the use of the compositions for examining the renal function, and to a kit for preparing such compositions.Type: GrantFiled: March 23, 1992Date of Patent: July 19, 1994Assignee: Mallinckrodt Medical Inc.Inventor: Dennis L. Nosco
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Patent number: 5330737Abstract: The present invention relates particularly to novel aminothiol ligands that are suitable for complexing with a radionuclide, such as Tc, Re, or Ga, and are useful as general imaging agents for diagnostic purposes. The ligands have the general formulae (I) and (II): ##STR1## wherein for formula I, R.sup.1 -R.sup.4, R.sup.6, R.sup.7 and R.sup.9 -R.sup.14 can each be one of H, alkyl, aryl, hydroxyalkyl, alkoxycarbonyl, etc.; R.sup.5 and R.sup.8 are suitable sulfur protecting groups; m and n are 1-3; B can be one of C(O)CHR.sup.6 CHR.sup.7 SR.sup.8, CHR.sup.9 CHR.sup.10 C(O)NHR.sup.11, or C(O)CHR.sup.12 CHR.sup.13 NHR.sup.14 ;and wherein for formula II, R.sup.15 -R.sup.18, R.sup.20 and R.sup.21 are defined in the same manner as R.sup.1 above; D and E are either C(O) or CHR.sup.17 ; F is either (CH.sub.2).sub.d NR.sup.18 (CH.sub.2).sub.e SR.sup.19 or CHNR.sup.20 R.sup.21 (CH.sub.2).sub.f SR.sup.22 ; R.sup.19 and R.sup.22 are defined in the same manner as R.sup.5 above; d, e and f are 1-3.Type: GrantFiled: December 6, 1991Date of Patent: July 19, 1994Assignee: Mallinckrodt Medical, Inc.Inventor: Raghavan Rajagopalan
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Patent number: 5326856Abstract: This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.Type: GrantFiled: April 9, 1992Date of Patent: July 5, 1994Assignee: Cytogen CorporationInventors: Daniel J. Coughlin, Benjamin A. Belinka, Jr.
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Patent number: 5324502Abstract: Radiopharmaceuticals for imaging myocardial tissues are prepared by forming lipophilic, cationic complexes of radioactive metal ions with metal chelating ligands comprising the Schiff base adducts of triamines and tetraamines with optionally substituted salicylaldehydes. The lipophilic, cationic, radioactive complexes of the invention exhibit high uptake and retention in myocardial tissues. Preferred gallium-68(III) complexes in accordance with this invention can be used to image the heart using positron emission tomography.Type: GrantFiled: April 2, 1992Date of Patent: June 28, 1994Assignee: Purdue Research FoundationInventors: Mark A. Green, Brenda W. Tsang
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Patent number: 5324824Abstract: A method for preparing a coordination complex of an isonitrile ligand and a radioisotope of Tc, Ru, Co, Pt, Re, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Nb and Ta from a non-radioactive metal adduct of the isonitrite.Type: GrantFiled: March 12, 1991Date of Patent: June 28, 1994Assignee: The DuPont Merck Pharmaceutical Co.Inventors: Alan B. Carpenter, Jr., Leo J. Maheu, Michael A. Patz, Thomas H. Tulip, Karen E. Linder, Vinayakam Subramanyam, Jeffery S. Thompson