METHOD FOR CREATING HYPERPOLARIZATION AT MICROTESLA MAGNETIC FIELDS

• US 20200132788A1
• Filed: 05/12/2018
• Published: 04/30/2020
• Est. Priority Date: 05/12/2017
• Status: Active Grant

• Current Assignee: Duke University, Vanderbilt University
• Original Assignee: Board of Trustees of Southern Illinois University, Duke University, Vanderbilt University
• Inventors: Chekmenev, Eduard Y., Barskiy, Danila A., Shchepin, Roman V., Warren, Warren S., Theis, Thomas, Goodson, Boyd
• Granted Patent: US 11,016,152 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 49/10 Organic compounds
• CPC Class Codes: G01R 33/282 Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent
• CPC Class Codes: G01R 33/445 MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging

Abstract

Provided are methods for nuclear spin polarization enhancement via signal amplification by reversible exchange at very low magnetic fields. The spin polarization is hyperpolarization of isotopically enriched heteronuclei by using a catalyst and parahydrogen to create a complex using iridium and applying magnetic fields in the microtesia range to transfer the spin order from parahydrogen to the complex.

Claims

1. A method of hyperpolarizing heteronuclei, the method comprising:

(a) combining a plurality of molecules of parahydrogen, a plurality of molecules of a catalyst, and a plurality of molecules of a compound, where the compound includes a heteronucleus and another atom that exists naturally as either a quadrupolar or a non-quadrupolar isotope, where the heteronucleus in at least 50% of the plurality of molecules of the compound is a hyperpolarizable heteronucleus, and where the plurality of molecules of the compound have been modified so as to isotopically enrich the other atom with the non-quadrupolar isotope, and where the parahydrogen, the compound and the catalyst associate to form a complex; and

(b) applying a magnetic field with a strength of less than 50 μ

T to the complex, thereby transferring the spin order from the parahydrogen to the hyperpolarizable heteronucleus associated with the complex.

2. The method of claim 1, where the other atom is a nitrogen atom, and the plurality of molecules of the compound have been modified so as to isotopically enrich the nitrogen atom with ¹⁵N.

3. The method of either of claim 1 or claim 2, where the other atom is a hydrogen atom, and the plurality of molecules of the compound have been modified so as to isotopically enrich the hydrogen atom with ¹H.

4. The method of any of claims 1-3, where the hyperpolarizable heteronucleus is ¹³C.

5. The method of any of claims 1-3, where the hyperpolarizable heteronucleus is ¹⁹F.

6. The method of any of claims 1-3, where the hyperpolarizable heteronucleus is ¹⁵N, ²⁹Si, ³¹P, ¹²⁹Xe, ⁷Li, ⁸⁹Y, ¹⁰⁷Ag or ¹⁰⁹Ag.

7. The method of any of claims 1-6, where the spin order is transferred during a temporary association of parahydrogen, the compound, and the catalyst while maintaining the chemical identity of the compound.

8. The method of any of claims 1-7, where the magnetic field is determined by matching the resonance frequency of parahydrogen with the resonance frequency of at least one hyperpolarizable nucleus of the compound.

9. The method of any of claims 1-8, where the magnetic field has a strength of less than 20 μ

T.

10. The method of any of claims 1-9, where the magnetic field has a strength of about 0.1 to about 1 μ

T.

11. The method of any of claims 1-10, where the catalyst is a heterogeneous catalyst.

12. The method of any of claims 1-10, where the catalyst is a homogeneous catalyst.

13. The method of any of claims 1-12 where the catalyst comprises a transition metal.

14. The method of claim 13, where the transition metal in the complex coordinates with the other atom.

15. The method of either of claim 13 or claim 14, wherein the transition metal is iridium.

16. The method of any of claims 1-15, where the catalyst is activated prior to forming the complex, and the pre-activation catalyst is [IrCl(COD)(IMes)].

17. The method of any of claims 1-10 and 13-16, where the catalyst is a homogeneous or heterogeneous catalyst, wherein the catalyst accommodates the simultaneous exchange of para-H₂ and heteronuclear spin center(s), and wherein the condition of spin-spin (weak or strong J) coupling between para-H₂ derived protons and heteronuclear spin center(s) is maintained.

18. The method of any of claims 1-17, where the compound is a contrast agent for an in vivo imaging technique.

19. The method of any of claims 1-18, where the heteronucleus is a first heteronucleus and the compound further includes a second heteronucleus, where the second heteronucleus in at least 50% of the plurality of molecules of the compound is a hyperpolarizable heteronucleus, wherein when the first and second heteronuclei are both hyperpolarizable, the first and second heteronuclei are a J-coupled pair;

wherein upon applying the magnetic field with a strength of less than 50 μ

T to the complex, the spin order from the parahydrogen is transferred to the J-coupled pair, thereby inducing a hyperpolarized long-lived spin state.