Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1994-10-31
1997-11-18
Seidleck, James J.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
424 936, 424 942, A61K 5100
Patent
active
056884869
DESCRIPTION:
BRIEF SUMMARY
This application is 371 of PCT/GB93/00279 filed on Feb. 11, 1993.
BACKGROUND OF THE INVENTION
This invention relates to the use of macromolecular compounds having tight molecular meshes, for example non-diamond carbon allotropes and in particular carbon-based macromolecular structures such as fullerenes, graphite and amorphous carbons, as therapeutic or diagnostic agents, in particular as contrast enhancing agents for contrast media for diagnostic imaging procedures, especially magnetic resonance imaging (MRI), magnetometric imaging (MSI), electrical impedance tomography (EIT), X-ray, ultrasound and scintigraphy.
Contrast agents may be administered in medical imaging procedures, for example X-ray, magnetic resonance and ultrasound imaging, to enhance the image contrast in images of a subject, generally a human or non-human animal body. The resulting enhanced contrast enables different organs, tissue types or body compartments to be more clearly observed or identified. In X-ray imaging the contrast agents function by modifying the X-ray absorption characteristics of the body sites in which they distribute; magnetic resonance contrast agents generally function by modifying the density or the characteristic relaxation times T.sub.1, T.sub.2 and T.sub.2 * of the nuclei, generally water protons, from the resonance signals of which the images are generated; scintigraphic contrast agents (a term used herein to include PET contrast agents) act as emitters of detectable radiation; and magnetometric contrast agents act by creating peturbations in the magnetic field in the body zones into which they distribute, peturbations which can be detected for example by SQUID magnetometers; and ultrasound contrast agents function by modifying the speed of sound or the density in the body sites into which they distribute.
The X-ray contrast agents first developed, barium sulfate and sodium iodide, have been superseded by iodinated organic compounds, in particular triiodophenyl compounds. Proposals have also been made to utilize the X-ray absorption properties of the lanthanides and other high atomic number metals to develop contrast agents with improved X-ray attenuation especially at the wavelengths used in CT; however these attempts have generally been relatively unsuccessful.
Thus, for example, Nalbandian et al. (see Ann. N. Y. Acad. Sci. 78: 779 (1959)) and Shapiro et al. (see Ann. N. Y. Acad. Sci. 78: 756 (1959)) proposed the use of the diethylenetriaminepentaacetic acid (DTPA) chelate of bismuth (BiDTPA) and the ethylenediaminetetraacetic acid (EDTA) chelate of lead (PbEDTA) as radiographic contrast agents but encountered problems of solubility and toxicity. In U.S. Pat. No. 4,176,173 Winchell et al. described the use of simple hafnium or tantalum complexes as X-ray contrast agents and more recently, ytterbium DTPA has been studied as an intravascular X-ray contrast agent, and an LD.sub.50 of 10 mmoles/kg has been reported (see Unger et al. Invest. Radiol. 21: 802 (1986)).
In MRI, the use of paramagnetic metal ions, such as Mn(II), as contrast agents was first proposed by Lauterbur et al. in 1978 (see pages 752-759 in "Electrons to Tissues--Frontiers of Biological Energetics" Vol. 1, edited by Dutton et al., Academic Press, New York, 1978) and since that time a wide range of paramagnetic metal ion chelate complexes have been proposed for use in MRI. Thus for example Schering AG in U.S. Pat. No. 4,647,447 propose the use of salts of gadolinium(III) chelates of DTPA. More recently the use of superparamagnetic particles as MRI contrast agents has been described by Jacobsen in U.S. Pat. No. 4,863,715.
Whilst metal chelate contrast agents are used in MRI, they are not directly suitable for all applications (e.g. visualisation of certain body areas such as the gastrointestinal (GI) tract) and in certain cases concerns exist regarding their stability and side effects. Attempts have been made to achieve tissue-specific MRI contrast enhancement or to enhance stability and/or relaxivity by coupling of the paramagnetic chelates,
REFERENCES:
patent: 5177248 (1993-01-01), Chiang et al.
patent: 5248498 (1993-09-01), Neumann et al.
Fellmann Jere D.
Jamieson Gene C.
Klaveness Jo
Vogt Nils B.
Watson Alan D.
Nycomed Salutar Inc.
Seidleck James J.
Williamson Michael A.
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