Ge Healthcare Limited

Amersham International Plc

Amersham Plc

Nycomed Amersham Plc

Peter Knox

Anthony Eamon Storey

Marivi Mendizabal

Ian Andrew Wilson

Alan Michael Forster

Susan Champion

Benedicte Guilbert

Alex Gibson

Klaes Golman

Timothy Charles Richardson

Neil Cook

Jan Henrik Ardenkjaer-Larsen

Haukur Johannesson

Jan Wolber

Nigel Bosworth

Gary Robert Bower

Oksar Axelsson

Jan Jenrik Ardenkjaer-Larsen

Mike Looker

Karen Jane Barnes

Albie Santos

Jan Amersham Pharmacia Biotech Uk Ltd Wolber

Nigel Amersham Pharmacia Biotech Uk Ltd Bosworth

Albie Amersham Pharmacia Biotech Uk Ltd Santos

Jan H Nycomed Innovation Ab Ardenkjaer-Larsen

Mike Amersham Pharmacia Biotech Uk Ltd Looker

Klaes Nycomed Innovation Ab Golman

The invention is concerned with Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI), particularly NMR spectroscopy. It provides hyperpolarization methods offering enhanced sensitivity of detection over conventional NMR for studying the fate of a test compound in a biological system. The methods are particularly suitable for studying metabolism and toxicity of drugs. The resulting NMR sensitivity increase is advantageous in two key aspects of NMR detection: test compounds can be detected at lower concentrations and substantial time saving can be achieved in cases where extensive averaging is conventionally employed to increase the signal to noise ratio of the corresponding NMR spectra. The methods can be used for studios that were not practical or not possible using conventional NMR.

Method for investigating the fate of a test compound or the stateof a biological system by means of NMR of hyperpolarised NMR active nuclei

An in vitro assay method which comprises the use of an assay reagent containing at least one NMR active nucleus, and hyperpolarising at least one NMR active nucleus of the assay reagent; and analysing the assay reagent and/or the assay by NMR spectroscopy and/or NMR imaging. The assay reagent may contain an artificially high concentration of an NMR active nucleus.

NMR spectroscopic in vitro assay using hyperpolarization

Synthetic analogues of lysine and glutamine are provided which function as substrates for the fibrin-stabilising enzyme Factor XIIIa even when labelled with a detectable moiety. The use of suitable protecting groups provides compounds which possess reduced susceptibility to in vivo metabolism especially by peptidases, and are hence useful agents for the diagnosis of thrombosis, embolism, atherosclerosis, inflammation or cancer.

Labelled glutamine and lysine analogues

A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula (Y)-A-NHR)can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.

Labelled factor XIIIa substrates

A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula &mdash;(Y) &mdash;A&mdash;NHR, can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.

A human leucocyte elastase (HLE) inhibitor labelled with a detector moiety where the inhibitor is synthetic and has a molecular weight of less than 2000, is useful for the diagnostic imaging of sites of inflammation of infection in vivo, for labelling leucocytes in vitro, or for radiotherapy of rthritis. The HLE inhibitor is preferably a &bgr;-lactam or an azetidinone.

Labelled elastase inhibitors

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Chalfont St. Giles, United Kingdom

Peter Knox