Ge Healthcare As

Nycomed Imaging As

Ge Healthcare Limited

Mikkel Jacob Thaning

Peter Miller

Klaes Golman

Andrew Michael Leach

Andreas Richard Meijer

Rolf Servin

Lars-Goran Wistrand

Sven Goran Andersson

Andreas Olsson

Christian Glogard

Oskar Axelsson

Torsten Almen

Michael James Rishel

Brian Christopher Bales

David Key Dietrich

Ben Newton

Jan-Henrik Ardenkjaer-Larsen

Anna Rydbeck

Graham John Cotton

Duncan George Wynn

Jan Henrik Ardenkjaer-Larsen

Stefan Petersson

Haukur Johannesson

Jan Wolber

Paritosh Jayant Dhawale

Mathilde H Lerche

Georg Hansson

Khalid Hussain

Sondre Nilsen

Arne Wang Aabye

Jan Cervenka

Dirk-Jan In't Veld

Finn Radner

Nicolas Lasbistes

Ingvil Gausemel

Christian Gloegaard

Robert James Domett Nairne

Lennart Hansson

Herbert Baumann

Mark Howard

Karina Langseth

Oskar H E Axelsson

Lars-Göran Wistrand

Anders Brathe

Paul Alexander Jones

Steffen Bugge

Silalahi Sumihar

Deirdre Cassidy

Concetta Valeria Gringeri

Paul Michael Evans

Karl Andreas Gram

Anna Rydeck

Rene Zandt

Jarle Andre Haugan

Nikolai Enes

Salvatore Desena

Sven Andersson

Eric J Telfeyan

Lars-Goeran Wistrand

Christian GLØGÅRD

Jan Henrik ARDENKJÆR-Larsen

David B Whitt

Duncan Wynn

René in't Zandt

The present invention relates to a method of removal of metal ion impurities, such as calcium, from lanthanide metal complexes of macrocyclic chelators. The method uses a scavenger resin to remove metal ions, displaced from chelator, by an excess of lanthanide ions. Also provided is a method of preparation of MRI contrast agents, from the purified lanthanide metal complex, by the addition of a defined excess chelator.

Lanthanide complex formulations

The invention provides compounds suitable for use as contrast agents in magnetic resonance imaging (MRI). The compounds of the present invention are manganese (II) complexes having advantageous properties as compared with similar known compounds.

Chelate compounds

The present invention relates to a method of preparation of formulations of lanthanide metal complexes of macrocyclic chelators which further comprise a small excess of free chelator. The method uses a solid phase-bound scavenger chelator to remove excess lanthanide metal ions, prior to the addition of a defined excess chelator. Also provided is a method of preparation of MRI contrast agents, together with solid-phase bound chelator meglumine salts useful in the methods.

Metal complex formulations

The present invention relates to in vivo imaging and in particular to magnetic resonance imaging (MRI). Provided by the present invention is a pharmaceutical formulation suitable for use in an MRI procedure and which offers advantages over known such formulations. A particular dose of the pharmaceutical formulation of the invention is also envisioned as well as the use of said dose in a method of in vivo imaging. This present invention provides for simultaneous administration of a liver specific agent and a second MR contrast agent that is capable of better/further enhancing the dynamic vascular phase in a patient. The method of the invention has the advantage of simplicity and patient comfort, compared to sequential injections. Furthermore, the method of the invention provides the advantage that it can enable a lower cumulative dose of contrast agents.

Combination formulation

The present invention provides methods for the preparation of compounds useful in in vivo therapeutic and diagnostic applications. In particular, the present invention provides a method for the synthesis of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and also methods for the preparation of metal chelates of DOTA.

DOTA synthesis

Manganese chelate compounds

The present invention relates to a method of preparation of formulations of gadolinium metal complexes of the macrocyclic chelator DOTA, which further comprise a small excess of free DOTA. The method uses controlled conditions such that excess gadolinium is present as a precipitate of gadolinium oxide, with filtration to remove the excess, prior to the addition of a defined excess of DOTA chelator. Also provided is a method of preparation of MRI contrast agents based on Gd-DOTA.

Formulations of metal complexes

The present invention relates to X-ray examinations and to the improvement of patient safety during such. More specifically the invention relates to X-ray diagnostic compositions having low concentrations of iodine and an optimized amount of electrolytes. The invention further relates to methods of X-ray examinations wherein a body is administered with an X-ray diagnostic composition comprising a low concentration of iodine and irradiated with a radiation dose.

X-ray imaging contrast media with low iodine concentration and X-ray imaging process

The present invention relates to a process for purification of iodinated X-ray contrast agents and in particular to purification of crude dimeric contrast agents, such as Iodixanol and Ioforminol. More particularly, the invention relates to purification of such X-ray contrast agents using membrane technology to remove monomeric impurities.

Purification of X-ray contrast agents

The present invention relates to a process for the preparation of iodinated X-ray contrast agents and in particular to key intermediates thereof. More particularly, the invention relates to a work-up process for preparation of a compound mixture comprising 1-formylamino-3,5-bis(2,3-bis(formyloxy)propan-1-ylcarbamoyl)-2,4,6-trioodobenzene, a key intermediate in the process for preparing Ioforminol. Further, the invention relates to a process for preparing Ioforminol, a contrast agent useful in X-ray imaging.

Preparation of an intermediate compound of ioforminol

The present invention relates to a process for the preparation of Ioforminol, a contrast agent useful in X-ray imaging. More particularly, the invention relates to preparation of Ioforminol from a compound mixture comprising 1-formylamino-3,5-bis(2,3-bis(formyloxy)propan-1-ylcarbamoyl)-2,4,6-trioodobenzene by a process comprising in situ hydrolysis and a bis-alkylation.

Preparation of ioforminol, an x-ray contrast agent

The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula R&#x2014;N(CHO)&#x2014;X&#x2014;N(R)&#x2014;R wherein X denoted an optionally substituted alkylene group, Rdenotes a hydrogen atom or an acyl function and each R denotes a triiodinated phenyl residue further substituted by hydrophilic moieties. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Contrast agents

The invention relates to a dynamic nuclear polarisation method for producing hyperpolarised carboxylates of organic amines and amino compounds and compositions for use in that method. The DNP agent preferably is a stable oxygen-based, sulphur-based or carbon-based trityl radical. Optionally a paramagnetic metal ion is present.

Method to produce hyperpolarised carboxylates

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Oslo, Norway

Mikkel Jacob Thaning