Neorx Corporation

Mallinckrodt Medical, Inc.

Other

Biosynthema Inc.

G.d. Searle & Company

Ananthachari Srinivasan

Alan R Fritzberg

Sudhakar Kasina

Raghavan Rajagopalan

David S Jones

Daniel S Wilbur

Vivekananda M Vrudhula

John M Reno

Linda M Gustavson

Jeffrey N Fitzner

Jean-Luc VanderHeyden

Tripuraneni N Rao

Mark D Hylarides

T Jeffrey Dunn

Joseph E Bugaj

David C Anderson

Paul G Abrams

Leon R Lyle

Mary Marmion Dyszlewski

James A Sanderson

Michelle A Schmidt

Diana I Brixner

Jack L Erion

Daniel L Flynn

Donald B Axworthy

Alton C Morgan, Jr

Larry P Feigen

Jeffery Alan Zablocki

Dennis W Wester

Jean-Luc Vanderheyden

Philip Needleman

Peptide analogs of neurotensin are disclosed which are resistant to enzymatic degradation and which retain high binding affinity for neurotensin receptors. Pharmaceutical compositions of these compounds are useful for diagnostic and therapeutic purposes.

Labeled neurotensin derivatives

Stable analogs of cyclic peptides containing disulfide linkages are disclosed. The disulfide linkage is modified by one of four methods: (a) sulfide contraction, (b) isosteric substitution, (c) thioketal expansion, or (d) alkylation expansion. In sulfide contraction the disulfide bond (&mdash;S&mdash;S&mdash;) is replaced with a monosulfide bond (&mdash;S&mdash;) in which a bifunctional effector molecule, such as a ligand or chemotoxic agent, is bound to the new peptide linkage. In isosteric substitution, one sulfur atom is replaced with a carbon atom and at least one of the carbon atoms at the modified site is a bifunctional effector molecule. In thioketal expansion, an alkylidene unit (&mdash;CR C &mdash;) is inserted between the two sulfur atoms. In alkylation expansion, an alkyl moiety of from C to C , is inserted between the two sulfur atoms.

Stable analogs of bioactive peptides containing disulfide linkages

A radiopharmaceutical capable of localizing at a site of thrombus containing activated platelets within a mammalian body is provided wherein the radiopharmaceutical comprises a linear peptidomimetic containing ligand capable of specifically binding to the GPIIb/IIIa integrin receptor of platelets in the thrombus and a radionuclide covalently bound to the peptidomimetic containing ligand. The ligand compositions of the invention are provided complexed with a selected metal radionuclide to form a diagnostic or therapeutic radiopharmaceutical to image a site of thrombus or provide radiotherapy to the site of thrombus, respectively. Methods of imaging a site of thrombus in a mammalian body by administering a diagnostically effective amount of the radiopharmaceutical composition of this invention complexed with a selected diagnostic metal radionuclide and methods of providing therapy to a site of thrombus in a mammalian body by administering a therapeutically effective amount of the radiopharmaceutical composition of this invention complexed with a selected therapeutic metal radionuclide are also provided as well as kits for preparing such radiopharmaceutical compositions.

Radiopharmaceutical compositions capable of localizing at sites of

This invention relates to radiolabeled peptide compositions for radiopharmaceutical use and, more specifically, to radiolabeled peptides for diagnostic or therapeutic use having an unmodified carboxy terminal amino acid. The radiopharmaceutical composition may be used for targeting a selected biological site. The radiolabeled peptide is characterized by having its carboxy terminal amino acid in its carboxylic acid form and the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent. The radiopharmaceutical composition preferably comprises a radiolabeled peptide selected from the group consisting of somatostatin, an analog of somatostatin, a derivative of somatostatin and peptides capable of binding to the somatostatin receptor, where the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent has its carboxy terminal amino acid in its carboxylic acid form.

Radiolabeled peptide compositions for site-specific targeting

Peptide compositions and method of radiolabeling

Compositions and methods of incorporating ligand precursors and ligands at any location within a peptide during peptide synthesis are disclosed. Derivatives of 2,4,5-triaminopentanoic acid and .gamma.-aminoglutamic acid are selectively incorporated into the peptide during solid phase or liquid phase synthesis, depending upon the choice of protecting groups. Ligand synthesis may then be completed at a later time to produce N.sub.3 S, N.sub.2 S.sub.2, and EDTA type chelating agents.

Ligand precursors for incorporation into peptides

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 monoaddition 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.

Method for preparing radiolabeled peptides

Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.

Metal-radionuclide-labeled proteins and glycoproteins for diagnosis and

The present invention relates particularly to novel pyridine based nitrogen-sulfur ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes, novel aminothiol ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes, and amide-thiolate ligands having improved metal chelate formation kinetics. The amide-thiolate ligands include an amine which converts to a vinylogous amide upon complexation, thereby providing rapid complexation and thermodynamic stability. The ligands may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.

Ligands useful in radiographic imaging

The present invention relates particularly to novel imidazole based nitrogen-sulfur ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes.

Imidazole based nitrogen-sulfur ligands useful in radiographic imaging

The present invention relates particularly to novel heterocycle based nitrogen-sulfur ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes.

Heterocycle based nitrogen sulfur ligands useful in radiographic imaging

The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ('N.sub.2 S.sub.3 '), two nitrogen atoms and four sulfur atoms ('N.sub.2 S.sub.4 '), or three nitrogen atoms and three sulfur atoms ('N.sub.3 S.sub.3 '). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re. The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment. Another aspect of the invention provides kits for producing chelate-targeting agent conjugates for radiopharmaceutical use. An additional aspect of the invention provides methods for using the chelate-targeting agent conjugates for diagnostic and therapeutic purposes, such as detection of a target site and delivery of a radionuclide to the site, respectively.

Metal radionuclide chelating compounds for improved chelation kinetics

Imidazole based nitrogen sulfur ligands useful in radiographic imaging

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.

Growing community of inventors

Kirkland, WA, United States of America

Ananthachari Srinivasan