Use of macrocyclic metal complexes as temperature sensors

Details Use of macrocyclic metal complexes as temperature sensors Use of macrocyclic metal complexes as temperature sensors

1996-03-08

1998-05-05

Hollinden, Gary E.

Drug, bio-affecting and body treating compositions

In vivo diagnosis or in vivo testing

Magnetic imaging agent

534 16, 540465, 540474, 436173, 524184, 524836, A61B 5055

Patent

active

057470006

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/EP94/01376 filed Apr. 29, 1994, published as WO94/27977 Dec. 8, 1994.
The invention relates to the object characterized in the claims, i.e., the magnetic resonance! diagnosis.
With the aid of modern diagnostic methods, it is possible to depict extremely small morphological structures at a resolution that comes close to that of the tissue sections of anatomy textbooks. This enormously high resolution is achieved, on the one hand, by constantly improved hardware, but, on the other hand, also with the aid of contrast media. With the various known methods, such as ultrasonic diagnosis, diagnostic radiology, nuclear medicine and even nuclear spin tomography, however, it is not possible to obtain information on the metabolic-physiological state of a tissue in the living organism. For a more exact diagnosis and especially for planning and monitoring the course of therapeutic intervention, however, such knowledge is of considerable importance, since an optimum treatment can be successful only if a statement on its effect is possible early on.
It is known that an important factor in metabolic-physiological activity is temperature. The determination of this tissue temperature provides important information on the function and state of the cells, so that it is desirable to locate sites that have temperatures which deviate from normal body temperature. This makes it possible to identify pathologically altered tissue and optionally to perform treatment.
Body temperature is a product of the activity of energy metabolism and is subject to varied influences.
Blood flow represents a significant value of influence on local tissue temperature; via blood flow the body attempts to offset temperature drops (Editors), Springer Verlag, 23rd Edition, 1987!. The measurement of temperature therefore offers a way to delimit local increased blood circulation (e.g., in the case of inflammations) or restricted blood circulation (e.g., in ischemic regions) in a tissue against its healthy environs.
In the case of hyperthermia treatment for tumor diseases, the measurement of tissue temperature is an important parameter for monitoring the course of the radiation. At the moment, only invasive methods can be used for Hyperthermia in Cancer Treatment, Cancer Research, 44 (Suppl.), 4703s-4709s, 1984!.
It is now known that the chemical shift of signals in in vitro NMR spectroscopy is also a function of temperature. This influence is caused by intermolecular and intramolecular interactions. In high-resolution NMR spectroscopy, intermolecular interactions, e.g., with the solvent, quite decisively determine the chemical shift. The solvation of the molecule under study, including intermolecular aggregation and hydrogen bridging, depends greatly on temperature. Hydrogen bridge bonds are broken at elevated temperatures and thus change the chemical environment of the atomic nuclei. In the case of substances that form strong intermolecular hydrogen bridge bonds, the temperature coefficient of the chemical shift is especially large. With the aid of calibration curves, temperature can then be determined exactly from the chemical shift that is measured empirically. In this case, particularly the aliphatic alcohols, which tend toward strong hydrogen bridge bonds, have proven to be of value: T=409.0-36.54.DELTA..delta.-21.85(.DELTA..delta.).sup.2 which .DELTA..delta. is the difference in the chemical shifts between the Merbach, Rev. Sci. Instrum. 36, 1896 (1965)!.
The change in the chemical shift with temperature due to intermolecular interaction is by no means limited to the proton; rather it is a general property of all magnetically active atomic nuclei, so that a whole series of temperature standards have been proposed in the literature.


______________________________________ Temp.-gradient Standard Substance Atomic Nuclei ppm/K Literature* ______________________________________ Methanol proton 0.015 (1) ethylene glycol proton 0.016 (1),(9) CH.sub.2 I.sub.2 /cyclooctane carbon 0.07 (2) CH.sub.3 I/tetr

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