The General Hospital Corporation

Ortho Pharmaceutical Corporation

Johnson Matthey Inc.

Johnson Matthey Public Limited Company

Scott K Larsen

Randall B Lauffer

Gary James Bridger

John D Higgins, Iii

Howard F Solomon

Pedro E Hernandez

Alan J Fischman

Robert H Rubin

Robert L Suddith

H William Strauss

Daniel J Kroon

Michelle L Tomsho

Michael Bornstein

Claudia K Derian

Diane C Corbo

N Adeyinka Williams

Anthony J Fuccello

Mary Jean Link

A lyophilized imaging agent formulation and methods for making same are disclosed, such formulations comprise a targeting molecule such as antibody or chemotactic peptide, a linker such as diethylenetriaminepentaacetic acid (DTPA) or succinimidyl 6-hydrazinium nicotinate hydrochloride (SHNH), drying protectant such as mannitol, maltose or tricine, and excipient such as polysorbate 80, in citrate buffer. The formulations of the invention are lyophilized and may be stored stably for extended periods of time. Following reconstitution with diluent, the formulations are administered to a subject for scintigraphic imaging or therapeutic use. Also contemplated is a kit comprising a two-vial system wherein a first vial comprises a lyophilized formulation of imaging agent in the form of a lyophilized cake, and a second vial comprises a pharmaceutically acceptable carrier or diluent.

Lyophilized imaging agent formulation comprising a chemotactic peptide

The invention relates to a method of detecting a site of infection or inflammation, and a method for treating such infection or inflammation, in an individual by administering to the individual a diagnostically or therapeutically effective amount of detectably labeled, therapeutic, or therapeutically-conjugated, chemotactic peptide that accumulates substantially at the infected or inflamed site, said chemotactic peptide having the general structure

Labeled chemotactic peptides to image focal sites of infection or

An NMR contrast agent composition contains a complex of a selected metal ion and a selected ligand. The ion is selected from the group consisting of gadolinium (III), iron (III), manganese (II), manganese (III), chromium (III), copper (II), dysprosium (III), terbium (III), holmium (III), erbium (III), europium (II), and europium (III); and the ligand is a linear two-nitrogen compound having one 2-hydroxy-aryl group at one of the nitrogen; or the ligand is a linear two-nitrogen compound having one or two 2-hydroxy-aryl groups at each of the nitrogens; or the ligand is a linear three-, four-, or five-nitrogen compound having one or two 2-hydroxy-aryl substituents at each of one or more of the nitrogens, or the ligand is a heterocyclic compound having a ring containing three or four nitrogens, and having a 2-hydroxy-aryl substitent at one or more of the nitrogens; or the ligand is a heterocyclic compound having a ring containing 4 nitrogens, and having a carboxyl group at two of the nitrogens and an aromatic substituent at the other two of the nitrogens. Also, a method for enhancing the contrast in NMR imaging in a patient includes steps of preparing an NMR contrast enhancing agent by mixing an NMR contrast compound of the invention with a pharmaceutically acceptable carrier, introducing the NMR contrast enhancing agent into the patient, and subjecting the patient to NMR imaging.

Hydroxy-aryl metal chelates for diagnostic NMR imaging

An NMR contrast agent composition contains a complex of a selected metal ion and a selected ligand. The ion is selected from the group consisting of gadolinium (III), iron (III), manganese (II), manganese (III), chromium (III), copper (II), dysprosium (III), terbium (III), holmium (III), erbium (III), europium (II), and europium (III); and the ligand is a linear two-nitrogen compound having one 2-hydroxy-aryl group at one of the nitrogens: or the ligand is a linear two-nitrogen compound having one or two 2-hydroxy-aryl groups at each of the nitrogens; or the ligand is a linear three-, four-, or five-nitrogen compound having one or two 2-hydroxy-aryl substituents at each of one or more of the nitrogens, or the ligand is a heterocyclic compound having a ring containing three or four nitrogens, and having a 2-hydroxy-aryl substitent at one or more of the nitrogens; or the ligand is a heterocyclic compound having a ring containing 4 nitrogens, and having a carboxyl group at two of the nitrogens and an aromatic substituent at the other two of the nitrogens.

An NMR contrast agent composition contains a complex of a selected metal ion and a selected ligand. The ion is selected from the group consisting of gadolinium (III), iron (III), manganese (II), manganese (III), chromium (III), copper (II), dysprosium (III), terbium (III), holmium (III), erbium (III), europium (II), and europium (III); and the ligand is a linear two-nitrogen compound having one 2-hydroxy-aryl group at one of the nitrogens; or the ligand is a linear two-nitrogen compound having one or two 2-hydroxy-aryl groups at each of the nitrogens; or the ligand is a linear three-, four-, or five-nitrogen compound having one or two 2-hydroxy-aryl substituents at each of one or more of the nitrogens, or the ligand is a heterocyclic compound having a ring containing three or four nitrogens, and having a 2-hydroxy-aryl substitent at one or more of the nitrogens; or the ligand is a heterocyclic compound having a ring containing 4 nitrogens, and having a carboxyl group at two of the nitrogens and an aromatic substituent at the other two of the nitrogens.

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.

Complexes with .sup.99m Tc suitable for radiolabelling monoclonal

An NMR contrast agent composition contains a complex of a selected metal ion and a selected ligand. The ion is selected from the group consisting of gadolinium (III), iron (III), manganese (II), manganese (III), chromium (III), copper (II), dysprosium (III), terbium (III), holmium (III), erbium (III), europium (II), and europium (III); and the ligand is a linear two-nitrogen compound having one 2 hydroxy-aryl group at one of the nitrogens; or the ligand is a linear two-nitrogen compound having one or two 2-hydroxy aryl groups at each of the nitrogens; or the ligand is a linear three-, four-, or five nitrogen compound having one or two 2-hydroxy-aryl substituents at each of one or more of the nitrogens, or the ligand is a heterocyclic compound having a ring containing three or four nitrogens, and having a 2 hydroxy aryl substituents at one or more of the nitrogens; or the ligand is a heterocyclic compound having a ring containing 4 nitrogens, and having a carboxyl group at two of the nitrogens and an aromatic substituent at the other two of the nitrogens. Also, a method for enhancing the contrast in NMR imaging in a patient includes steps of preparing an NMR contrast enhancing agent by mixing an NMR contrast compound of the invention with a pharmaceutically acceptable carrier, introducing the NMR contrast enhancing agent into the patient, and subjecting the patient to NMR imaging.

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Boston, MA, United States of America

Scott K Larsen