Method of localizing and quantifying regional energy metabolism

Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant...

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252644, A61K 4902

Patent

active

051357356

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BRIEF SUMMARY
The invention relates to a method of localizing and quantifying regional energy metabolism, in particular regional ischemia, in a warm-blooded living being. The invention further relates to a pharmaceutical composition to be used for said method.
The diagnosis and localisation of ischemia in various organs in present clinical practice relies mainly on angiographic methods and the study of tissue perfusion using thallium scintigraphy. While angiography permits the localisation of diseased arteries, it does not allow to draw conclusions as to the functional consequence and extent of the ischemic process. Furthermore, it is often difficult to relate changes in tissue perfusion to abnormalities observed with angiographic techniques. In order to gain information into the dynamics of tissue metabolism during ischemia use was made of various positron emitting tracer substances. Previous studies have largely relied upon only a few tracers for example N-13 ammonia for blood flow, C-11 palmitate for fatty acid metabolism and F-18 2--fluoro-2-desoxyglucose (FDG) for glucose utilisation. None of these tracers however, permitted a direct insight into the dynamics of the energy metabolism, mainly because the metabolism of substances applied differs greatly from organ to organ and is dependent on the dietary state of the organism.
Thallium scintigraphy is only a measure of tissue perfusion but not suitable for assessing the dynamics of energy metabolism. Therefore this method has a serious restriction in evaluating and quantifying ischemia. Radiolabelled fatty acids have the drawback, that their kinetic behaviour is seriously influenced by other substrates which play a role in the metabolism of the organs to be investigated.


BRIEF DESCRIPTION OF THE DRAWING

The FIGURE illustrates a possible chemical reaction scheme for preparing -homocysteine thiolactone, a precursor of -homocysteine.
It is the object of the invention to enable the localization and quantification of regional energy metabolism, in particular of regional ischemia, without invasive methods and avoiding the above disadvantages. It has been found that this object can be achieved according to the present invention by administering to a warm-blooded living being a diagnostically effective quantity of a radiolabelled L-homocysteine or a radiolabelled functional derivative thereof.
The quantity of radioactive material effective for diagnosing depends on various factors such as the diagnostic method, e.g. planar scintigraphy or emission tomography, the radiolabel used and the organ to be examined. In case the method of the invention is used to localize and quantify regional ischemia, such ischemia does not only encompass cardiac ischemia but also includes ischemia of other organs like the brains and the gastro-intestinal tract. It will be obvious from the above, that the quantity of radioactive material which is effective for diagnosing purposes may vary within broad ranges. Generally the radioactive material is administered to the living being in a quantity of 1 to 1000 MBq per 70 kg of body weight. The radiolabel may be chosen from radionuclides selected from the group consisting of positron emitting nuclides and gamma radiation emitting nuclides. Functional derivatives of L-homocysteine are to be understood to include derivatives of L-homocysteine wherein the S-H function is intact, or, in case the radiolabel is selenium-73, wherein the .sup.73 Se-H function is intact.
A preferred radiolabelled compound to be used for the method of the invention is L-homocysteine or its functional derivative, labelled with a radioisotope selected from the group consisting of carbon-11, selenium-73, fluoride 18, bromine-76, bromine-77 and iodine-123. Typical positron emitting nuclides like carbon-11, selenium-73 and fluorine-18 enable the in vivo application of the labelled compounds by using the so-called "positron-emission tomography" (PET) technique. By using this technique a computer tomogram can be obtained of the organ to be investigated, e.g. the heart or the brains, e

REFERENCES:
Duerre, J. A. et al. "Radioisotopically Labeled S-Ribosyl-L-Homocysteine," J. Lab. Cmpos, vol. 4(2), 1968, pp. 171-180.
Kredich, N. M. et al. "A Sensitive Radiochemical . . . and L-Homocysteine," Anal Biochem, V. 116(2), 1981, pp. 503-510.
Ueland, P. M. et al., "Homocysteine in Tissues of the Mouse & Rat," J. Biol. Chem., V. 259(4), 1984, pp. 2360-2364.

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