Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1998-01-09
1999-08-31
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
424 961, 424 93, C07C22908
Patent
active
059455640
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to 2,2-dideutero-5-aminolevulinic acid useful as a contrast medium for MRI (magnetic resonance imaging). More specifically, the present invention relates to 2,2-dideutero-5-aminolevulinic acid and its salt, and a hydrate or a solvate thereof, and to a contrast medium for MRI comprising said substance as an essential component.
BACKGROUND ART
MRI is an excellent technique which can achieve accurate diagnosis of a disease by visibly imaging morphological alterations of a living tissue from a pathological viewpoint. MRI is one of diagnostic methods which have already been utilized widely. Currently available MRI, utilizing .sup.1 H as a detection nucleus, forms an image based on differences of relaxation time of .sup.1 H nucleus. The differences reflect water molecules existing in distinguishable environments in a living body which depend on a sort of a tissue they exist or depend on the presence or absence of pathological abnormality of a tissue.
Distinctions of different environments and sharpness of images can be achieved by influencing the relaxation time of .sup.1 H nucleus. MRI contrast media are often used for this purpose. MRI contrast media presently used are based on various kinds of concepts, however, it is common for all of the contrast media to be used for MRI diagnosis which utilizes .sup.1 H nucleus as a detection nucleus. These MRI contrast media are administered intravascularly, with some exceptions of certain contrast media for gastrointestinal tract. Accordingly, an advantage of MRI diagnosis, i.e., it causes almost no pain to a patient, is spoiled. Therefore, MRI contrast media have been desired which can be orally administered and cause little pain to patients.
Another class of MRI diagnostic techniques has also been studied in which water molecules in living bodies are not measured and an NMR-spectroscopically detectable nucleus is utilized as a detection nucleus other than .sup.1 H. For example, .sup.19 F, .sup.23 Na, .sup.31 P, and .sup.13 C can be used as the detection nucleuses. These techniques, utilizing a detection nucleus that does not exist in living tissues, enable an imaging which uses a detection nucleus as a tracer that is not detectable in MRI diagnosis utilizing .sup.1 H as a detection nucleus. These techniques also provide information about chemical shifts which cannot be obtained by MRI diagnosis utilizing .sup.1 H as a detection nucleus. Therefore, the techniques are extremely useful.
Deuterium (D=.sup.2 H) is a stable nucleus that can be NMR-spectroscopically detected (for example, Chem. Pharm. Bull. Vol. 38, No. 9, pp.2610-2613, 1990; and Development of superconductive type NMR system for in vivo molecules, Heisei-4, No. 03558029, p38, 1993). In addition, its natural existing ratio is quite a low level, i.e., 0.015% , which means almost no existence in living bodies. Therefore, MRI diagnosis utilizing deuterium as a detection nucleus is expected to be an extremely useful diagnostic method. Nevertheless, little study has been conducted about contrast media containing deuterium as a detection nucleus (see, for example, U.S. Pat. No. 5,042,488 and Japanese Patent Unexamined Publication No. (Hei)6-206883/1994).
Accordingly, an object of the present invention is to provide a contrast medium for MRI diagnosis which comprises deuterium as a detection nucleus. More specifically, the object is to provide a contrast medium which contains deuterium as a detection nucleus and have a high affinity to a specific tissue of a living body. Another object of the present invention is to provide a contrast medium for MRI diagnosis which has the aforementioned characteristic features and can be administered orally.
DISCLOSURE OF THE INVENTION
The inventors of the present invention conducted various researches to achieve the foregoing objects, and as a result, they found that 2,2-dideutero-5-aminolevulinic acid administered to a living body was detectable by MRI, and that the acid specifically accumulated in certain tissues in a living b
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Geist Gary
Keys Rosalynd
Mitsubishi Chemical Corporation
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