Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1992-01-21
1994-09-13
Hollinden, Gary E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424646, 424648, 424 5, 436173, 1286534, 128654, 514492, 514502, 514563, 514937, 562473, A61B 5055, A61K 31195
Patent
active
053466900
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to improvements in and relating to magnetic resonance imaging (MRI), and in particular to contrast media for use in MRI, especially of body cavities from which contrast media may be discharged from the body without passing through body tissue, in particular the gastrointestinal (GI) system.
MRI is now a well established medical diagnostic tool which is particularly attractive to physicians, at least in part due to its ability to differentiate between soft tissues and since it does not require the patient to be exposed to the potentially harmful ionizing radiation, e.g. X-radiation and gamma-radiation, of conventional radiography.
Although MRI can be carried out without using added contrast media, it has found that image contrast can be improved by administering to the patient substances which affect the nuclear spin reequilibration of the nuclei (hereinafter the "imaging nuclei"--generally water protons in body fluids and tissues) that are responsible for the magnetic resonance (MR) signals from which MR images are generated.
Accordingly, in recent years, many such substances have been suggested for use as MRI contrast agents. Thus, for example, in 1978 Lauterbur proposed the use of paramagnetic species, such as Mn(II), as MRI contrast agents (see Lauterbur et al., pages 752-759 in "Electrons to Tissues--Frontiers of Biological Energetics", Volume 1, edited by Dutton et al., Academic Press, New York, 1978). More recently Schering AG, in EP-A-71564, proposed the use of the dimeglumine salt of the gadolinium(III) chelate of diethylenetri-aminepentaacetic acid (GdDTPA-dimeglumine).
While MRI has until now mainly been used for imaging the central nervous system, the technique has great potential for imaging externally voided body cavities and especially the GI tract. However, development of MRI as a technique for imaging the GI tract, or indeed the abdomen in general, has been hindered by the special problems of imaging the abdomen in which, in the absence of a contrast agent, inter-tissue contrast is relatively poor. There is thus a general need for improved MRI contrast media suitable for imaging such body cavities.
Various substances have been evaluated as potential MRI contrast agents for the GI system, including for example paramagnetic compounds, perfluorochemicals and magnetically responsive particles (that is ferromagnetic, ferrimagnetic or superparamagnetic particles). In this regard, reference may be had to Wesbey et al. Radiology 149: 175-180 (1983), Runge et al. Radiology 147: 789-791 (1983), Laniado et al. Fortschr. Rontgenstr. 147: 325-332 (1987), Kornmesser et al. Fortschr. Rontgenstr. 147: 550-556 (1987), Claussen et al. Fortschr. Rontgenstr. 148: 683-689 (1988), Lonnemark et al. Acta Radiologica 29: 599 (1988), Lonnemark et al. Acta Radiologica 30: 193-196 (1989) Fasc. 2, Mattrey et al. AJR 148: 1259 (1987), and Wesbey et al. Magn. Reson. Imag. 3: 57-64 (1985) and to references therein.
Two products at least are now in clinical trials as oral MRI contrast media--suspensions of magnetically responsive particles (see Lonnemark et al. (1989) supra) and solutions of GdDTPA-dimeglumine (see Claussen et al. supra).
From a diagnostic point of view, magnetically responsive particles and paramagnetic metal chelates such as GdDTPA produce completely different contrast enhancements in MR images. Thus GdDTPA is a "positive" contrast agent, i.e. its effect of reducing the spin-lattice relaxation time (T.sub.1) of the imaging nuclei results in an iincrease in the image intensity for the body regions into which it distributes. Magnetically responsive particles on the other hand are "negative" contrast agents, so called since their effect of reducing the spin-spin relaxation time (T.sub.2) of the imaging nuclei outweighs the effect of T.sub.1 reduction and results in a decrease in the MR signal intensity from the body regions into which they distribute.
The two forms of contrast enhancement are in fact complementary--for some pathological structures positive MRI contrast media wi
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Gundersen Helge G.
Klaveness Jo
Hollinden Gary E.
Nycomed Imaging AS
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