Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1992-09-02
1997-02-04
Gupta, Yogendra N.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
544242, 544296, 546255, 546256, 546348, 549433, 585 24, 585 25, 585 26, A61K 4904, C07D31770, C07D33906
Patent
active
055995225
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of stable free radicals, in particular inert carbon radicals, as image enhancing agents in magnetic resonance imaging (MRI) as well as to contrast media containing such radicals and to the use of such radicals and their non-radical precursors in the manufacture of MRI contrast media.
MRI is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially harmful radiation, such as for example the X-radiation of conventional radiography.
This technique, however suffers from several serious drawbacks, including in particular the expense of manufacture and operation of the MRI apparatus, the relatively long scanning time required to produce an image of acceptable spatial resolution, and the problem of achieving contrast in the magnetic resonance (MR) images between tissue types having the same or closely similar imaging parameters, for example in order to cause a tissue abnormality to show up clearly in the images.
The expense of manufacture and operation of an MRI apparatus is closely associated with the strength of the magnetic field that the primary magnet in the apparatus is required to generate in order to produce images of acceptable spatial resolution in an acceptable time.
MR images are generated by manipulation of the MR signals detected from the sample, for example a human or animal body, placed in a magnetic field and exposed to pulses of radiation of a frequency (typically radiofrequency (RF)) selected to excite MR transitions in selected non-zero spin nuclei (the "imaging nuclei", which are generally water protons in body fluids) in the sample.
The amplitude of the induced MR signals is dependent upon various factors such as the strength of the magnetic field experienced by the sample, the temperature of the sample, the density of the imaging nuclei within the sample, the isotopic nature and chemical environment of the imaging nuclei and the local inhomogeneities in magnetic field experienced by the imaging nuclei.
Thus many techniques have been proposed for enhancing MR image quality, for example by increasing MR signal amplitude or by increasing the difference in MR signal amplitude between different tissue types.
The imaging parameters (nuclear density, T.sub.1 and T.sub.2) for tissues of interest may be altered and many proposals have been made for doing this by the administration of magnetically responsive materials into patients under study (see for example EP-A-71564 (Schering), EP-A-133674 (Schering) and WO-A-85/04330 (Jacobsen)). Where such materials, generally referred to as MRI contrast agents, are paramagnetic they produce significant reduction in the T.sub.1 of the water protons in the body zones into which they are administered or at which they congregate, and where the materials are ferromagnetic or superparamagnetic (for example as suggested by Jacobsen) they produce a significant reduction in the T.sub.2 of the water protons. In either case the result is enhanced (positive or negative) contrast in the MR images of such zones.
The contrast enhancement achievable by such agents in conventional MRI is relatively limited and it is generally not such as to allow a reduction in the image acquisition period or in the field strength of the primary magnet.
Utilisation of the spin transition coupling phenomenon known as dynamic nuclear polarisation or as the Overhauser effect to amplify the population difference between the ground and excited spin states of the imaging nuclei by the excitation of a coupled ESR transition in a paramagnetic species present in the sample being imaged has been described by Hafslund Nycomed Innovation AB in WO-A-88/10419.
This new technique for generating a MR image of the sample, which is hereinafter termed electron spin resonance enhanced magnetic resonance imaging (ESREMRI), or Overhauser MRI, involves exposing the sample to a first radiation of a frequency selected to excite nuclear spin transitions in selected nucl
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Almen Torsten
Andersson Sven
Golman Klaes
J.o slashed.rgensen Mikkel
Rise Frode
Gupta Yogendra N.
Nycomed Imaging AS
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