Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – X-ray contrast imaging agent
Patent
1992-11-24
1995-10-17
Hollinden, Gary E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
X-ray contrast imaging agent
556 1, 556 28, 556 50, 514184, 514492, 514836, A61K 4904
Patent
active
054588693
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP91/00587 filed on Mar. 27, 1991.
The present invention relates to the use in diagnostic imaging, in particular X-ray, ultrasound and scintigraphy of contrast agents comprising complexes of multinuclear moieties, and to contrast media containing such complexes.
All diagnostic imaging is based on the achievement of different signal levels from different structures within the body. Thus in X-ray imaging for example, for a given body structure to be visible in the image, the X-ray attenuation by that structure must differ from that of the surrounding tissues. The difference in signal between the body structure and its surroundings is frequently termed contrast and much effort has been devoted to means of enhancing contrast in diagnostic imaging since the greater the contrast between a body structure and its surroundings the higher the quality of the images and the greater their value to the physician performing the diagnosis. Moreover, the greater the contrast the smaller the body structures that may be visualized in the imaging procedure, i.e. increased contrast can lead to increased spatial resolution.
The diagnostic quality of images is strongly dependent on the inherent noise level in the imaging procedure--and the ratio of the contrast level to the noise level can thus be seen to represent an effective diagnostic quality factor for diagnostic images.
Achieving improvement in such a diagnostic quality factor has long been and still remains an important goal. In techniques such as X-ray and ultrasound, one approach to improving the diagnostic quality factor has been to introduce contrast enhancing materials, contrast agents, into the body region being imaged.
Thus in X-ray for example early examples of contrast agents were insoluble inorganic barium salts which enhanced X-ray attenuation in the body zones into which they distributed. More recently the field of X-ray contrast agents has been dominated by soluble iodine containing compounds such as those marketed by Nycomed AS under the trade names Omnipaque and Amipaque.
Much recent work on X-ray contrast agents has concentrated on aminopolycarboxylic acid (APCA) chelates of heavy metal ions and, recognising that effective imaging of many body sites requires localization at the body sites in question of relatively high concentrations of the metal ions, there have been suggestions that polychelants, that is substances possessing more than one separate chelant moiety, might be used to achieve this.
However we have now found that contrast enhancement may be achieved particularly effectively by the use of multinuclear complexes, that is complexes wherein the complexed moiety itself comprises two or more contrast enhancing atoms or for X-ray or ultrasound two or more heavy atoms.
For the sake of clarity, the word "atom" is used to refer to ionic and covalently bonded forms and not simply to isolated uncharged atoms. Moreover it will be understood that the complexed moiety, while it is polynuclear, is not so large as to be considered to be a particle itself. Thus it will generally have maximum dimensions of 80 .ANG. or less, especially 40 .ANG. or less.
Thus viewed from one aspect the invention provides a method of generating an image of a human or non-human animal, preferably mammalian, body which method comprises administering to said body a physiologically tolerable contrast enhancing amount of a multinuclear complex and generating an image of at least part of said body, e.g. by X-ray, ultrasound, or scintigraphy.
Viewed from a further aspect the invention also provides a multinuclear complex, especially a tungsten and/or molyblenum complex, for use as a diagnostic image contrast enhancing agent.
Viewed from a still further aspect the invention also provides a diagnostic imaging contrast medium comprising a multinuclear complex together with at least one sterile pharmaceutical carrier or excipient.
Viewed from another aspect the invention provides the use of a multinuclear complex for the manufacture of a contrast medium for u
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Almen Torsten
Berg Arne
Dugstad Harald
Kim Sook-Hui
Klaveness Jo
Hollinden Gary E.
Nycomed Salutar Inc.
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