# US 5,707,875 A · 170-Labeled phosphoric acid compound and method and apparatus for selective observation of nuclear magnetic resonance signals using the compound > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,707,875 A - Document ID: US5707875A - Status: Granted - Kind: A - Application number: 08/513,510 - Filed: 1995-08-10 - Granted: 1998-01-13 - Earliest claimed: 1994-08-11 - Assignees: Hitachi, Ltd. - Inventors: Mitsuru Tamura; Yoshinori Harada; Norio Shimizu; Kenji Yasuda - Web page: https://patentgrep.com/patent/US5707875A ## CPC - G01R 33/4608: {RF excitation sequences for enhanced detection, e.g. NOE, polarisation transfer, selection of a coherence transfer pathway} - Y10T 436/13: Tracers or tags - Y10T 436/16: Phosphorus containing - Y10T 436/166666: of inorganic phosphorus compound in body fluid - Y10T 436/24: Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract Using a mixed sample of a plurality of phosphoric acid compounds different in chemical structure as a sample for measurement, a .sup.31 P nuclear magnetic resonance signal obtained through polarization transfer between .sup.17 O and .sup.31 P is observed and signals obtained without polarization transfer are eliminated, whereby .sup.31 P nuclear magnetic resonance signal spectrum of an .sup.17 O-labeled phosphoric acid is selectively observed. For this purpose, a double resonance NMR detector capable of exciting .sup.17 O and .sup.31 P at the same time is connected to an NMR spectrometer, and using a pulse train which permits observation of a .sup.31 P nuclear magnetic resonance signal obtained through polarization transfer between .sup.17 O and .sup.31 P, a .sup.31 P nuclear magnetic resonance signal from the .sup.17 O-labeled phosphoric acid is observed, and signals for .sup.17 O-unlabeled .sup.31 P are eliminated. ## Claims ### Claim 1 A method for measuring nuclear magnetic resonance comprising labeling a phosphoric acid group contained in a sample with at least .sup.17 O , one atom and detecting a nuclear magnetic resonance signal due to the labeled phosphoric acid group in distinction from nuclear magnetic resonance signals due to unlabeled phosphoric acid groups by utilizing polarization transfer attributable to a spin-spin coupling between .sup.31 P and .sup.17 O. ### Claim 2 (depends on 1) A method according to claim 1, wherein said labeling is conducted by introducing an .sup.17 O-labeled phosphoric acid compound into an organism tissue by transportation in an organism. ### Claim 3 (depends on 1) A method according to claim 1, wherein a reagent containing an .sup.17 O-labeled phosphoric acid group is introduced from the outside of the organism by injection. ### Claim 4 (depends on 1) A method according to claim 1, wherein said at least one .sup.17 O atom is chemically bonded to .sup.31 P so as to provide spin-spin coupling between said at least one .sup.17 O and the .sup.31 P, whereby a nuclear magnetic resonance spectrum of the .sup.31 P is split and a line width of the nuclear magnetic resonance spectrum is enlarged as compared to an unlabeled phosphoric acid compound. ### Claim 5 A method for selective observation of a nuclear magnetic resonance signal which comprises using as a sample for measurement a material containing an .sup.17 O-labeled phosphoric acid compound containing at least one .sup.17 O atom in the phosphoric acid group at a rate higher than the natural isotopic abundance of .sup.17 O and a phosphoric acid compound containing .sup.17 O present at the natural isotopic abundance, eliminating .sup.31 P nuclear magnetic resonance signals made by the .sup.17 O-unlabeled phosphoric acid compound by using a pulse sequence which permits observation of a .sup.31 P nuclear magnetic resonance signal obtained through polarization transfer attributable to spin-spin coupling between .sup.17 O and .sup.31 P, and observing a .sup.31 P nuclear magnetic resonance signal made by the .sup.17 O-labeled phosphoric acid compound. ### Claim 6 (depends on 5) A method for measuring phosphoric acid metabolism of an organism by a method for selective observation of a .sup.31 P nuclear magnetic resonance signal according to claim 5, which comprises administering an .sup.17 O-labeled phosphoric acid compound to an organism capable of metabolizing phosphoric acid with the lapse of time, and observing a .sup.31 P nuclear magnetic resonance signal due to the labeled phosphoric acid group. ### Claim 7 (depends on 6) A method for controlling cell culture which comprises calculating a metabolism rate in microorganism cells, animal cells or plant cells from an amount of an .sup.17 O-labeled phosphoric acid compound consumed in a definite time, by a method for measuring phosphoric acid metabolism according to claim 6, and controlling a supply rate of nutrients to be supplied to the cells based on said metabolism rate. ### Claim 8 (depends on 6) A method for imaging phosphoric acid metabolism of an organism by a method for measuring phosphoric acid metabolism according to claim 6, which comprises observing a .sup.31 P nuclear magnetic resonance signal due to an .sup.17 O-labeled phosphoric acid group by a magnetic resonance imaging method or a magnetic resonance spectral method. ### Claim 9 (depends on 5) A method for measuring phosphoric acid metabolism of an organism by a method for selective observation of a .sup.31 P nuclear magnetic resonance signal according to claim 5, wherein said at least one .sup.17 O atom is chemically bonded to .sup.31 P so as to provide spin-spin coupling between said at least one .sup.17 O and the .sup.31 P, whereby a nuclear magnetic resonance spectrum of the .sup.31 P is split and a line width of the nuclear magnetic resonance spectrum is enlarged as compared to an unlabeled phosphoric acid compound. ### Claim 10 An apparatus for selective observation of a .sup.31 P nuclear magnetic resonance signal which comprises a container to accommodate a sample for measurement containing an .sup.17 O-labeled phosphoric acid compound having at least one .sup.17 O atom in its phosphoric acid group at a rate higher than the natural isotopic abundance of .sup.17 O and a phosphoric acid compound containing .sup.17 O present at the natural isotopic abundance, an irradiating coil for exciting .sup.17 O magnetically by a predetermined pulse sequence, an irradiating coil and detecting coil for exciting and observing .sup.31 P magnetically by a predetermined pulse sequence, at least two transmitters for applying voltages of predetermined frequencies to each of the irradiating coils for .sup.17 O and .sup.31 P, a receiver in which nuclear magnetic resonance signals from the sample through the observing coil are detected, and the detected nuclear magnetic resonance signals are subjected to a predetermined processing, followed by observing a .sup.31 P nuclear magnetic resonance signal from the .sup.17 O-labeled phosphoric acid compound, and a means for applying a predetermined magnetic field to the sample and the coils. ### Claim 11 (depends on 10) An apparatus for detecting a .sup.31 P nuclear magnetic resonance signal from adenosine diphosphate according to claim 10, wherein the frequency of a transmitter of .sup.31 P channel is adjusted to observe .beta.-.sup.17 O-labeled adenosine diphosphate having at least one .sup.17 O atom bonded to the phosphorus atom at its .beta.-position. ### Claim 12 (depends on 11) An apparatus for selective detection of a .sup.31 P nuclear magnetic resonance signal from adenosine diphosphate according to claim 11, wherein the frequency of the transmitter of .sup.31 P channel is adjusted to observe .beta.-.sup.17 O-labeled adenosine containing a plurality of phosphoric acid compounds as a mixture thereof. ### Claim 13 (depends on 12) An apparatus for selective .sup.31 P nuclear magnetic resonance spectral imaging of 8-.sup.17 O-labeled adenosine diphosphate having at least one .sup.17 O atom bonded to the phosphorus atom at its .beta.-position, comprising a mechanism capable of producing a gradient magnetic field and an apparatus for selective detection of a .sup.31 P nuclear magnetic resonance signal from adenosine diphosphate according to claim 12. ### Claim 14 (depends on 11) An apparatus for selective .sup.31 P nuclear magnetic resonance spectral imaging of .beta.-.sup.17 O-labeled adenosine diphosphate having at least one .sup.17 O atom bonded to the phosphorus atom at its .beta.-position, comprising a mechanism capable of producing a gradient magnetic field, and an apparatus for selective detection of a .sup.31 P nuclear magnetic resonance signal from adenosine diphosphate according to claim 11. ### Claim 15 (depends on 10) An apparatus for selective observation of a .sup.31 P nuclear magnetic resonance signal according to claim 10, wherein said .sup.17 O-labeled phosphoric acid compound has said at least one .sup.17 O atom chemically bonded to .sup.31 P so as to provide spin-spin coupling between said at least one .sup.17 O and the .sup.31 P, whereby a nuclear magnetic resonance spectrum of the .sup.31 P is split and a line width of the nuclear magnetic resonance spectrum is enlarged as compared to an unlabeled phosphoric acid compound.