Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate | Sciact - CRIS-system of Boreskov Institute of Catalysis

Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate Full article

Journal

ACS Sensors
ISSN: 2379-3694

Output data

Year: 2024, Volume: 9, Number: 2, Pages: 770–780 Pages count : 11 DOI: 10.1021/acssensors.3c02075

Tags

NMR , hyperpolarization, pyruvate , C-13, parahydrogen, laser, RASER

Authors

Nantogma Shiraz ¹ , de Maissin Henri ^2,3,4 , Adelabu Isaiah ¹ , Abdurraheem Abubakar ¹ , Nelson Christopher ⁵ , Chukanov Nikita V. ⁶ , Salnikov Oleg G. ⁶ , Koptyug Igor V. ^7,6 , Lehmkuhl Sören ⁸ , Schmidt Andreas B. ^1,2,3,4 , Appelt Stephan ^9,10 , Theis Thomas ^11,4,12 , Chekmenev Eduard Y. ^1,13

Affiliations

1	Department of Chemistry, Integrative Bio-Sciences (IBIO), Karmanos Cancer Institute (KCI), Wayne State University, Detroit, Michigan 48202, United States
2	Division of Medical Physics, Department of Radiology, Medical Center, University of Freiburg, Freiburg 79106, Germany
3	Faculty of Medicine, University of Freiburg, Killianstr. 5a, Freiburg 79106, Germany
4	German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany
5	Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States
6	International Tomography Center SB RAS, 630090 Novosibirsk, Russia
7	Boreskov Institute of Catalysis SB RAS, 630090 Novosibirsk, Russia
8	Institute of Microstructure Technology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Karlsruhe 76344, Germany
9	Central Institute for Engineering, Electronics and Analytics − Electronic Systems (ZEA-2), Forschungszentrum Jülich GmbH, Jülich D-52425, Germany
10	Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen 52056, Germany
11	Department of Physics, North Carolina State University, Raleigh, North Carolina 27606, United States
12	Joint UNC & NC State Department of Biomedical Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States
13	Russian Academy of Sciences, 119991 Moscow, Russia

Funding (15)

1	National Institutes of Health	R21EB025313
2	National Institute of Biomedical Imaging and Bioengineering	1R01EB029829
3	National Institutes of Health	R21EB033872
4	National Science Foundation	CHE-1904780
5	Wayne State University
6	German Cancer Research Centre (DKFZ)
7	Swagelok
8	University Medical Center Freiburg
9	German Research Foundation	SCHM 3694/1-1
10	German Research Foundation	SCHM 3694/2-1
11	German Research Foundation	SFB 1479
12	Federal Ministry of Education and Research	13N16448
13	Russian Science Foundation	21-73-10105 (121121600301-4)
14	Russian Science Foundation	22-43-04426
15	United States Department of Energy	DE-SC0023334

13C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of 13C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-13C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, 13C Radiofrequency Amplification by Stimulated Emission of Radiation (13C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (Q) of 32 for sample concentrations as low as 0.125 M with 13C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-13C]pyruvate, which are separated by 10 ppm in 13C NMR spectra. This is a good model system to study the simultaneous 13C RASER signals of multiple 13C species. This system models the metabolic production of hyperpolarized [1-13C]lactate from hyperpolarized [1-13C]pyruvate, which has a similar chemical shift difference. Our results show that 13C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, 13C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized 13C signals. The reported results pave the way to novel sensing approaches of 13C hyperpolarized pyruvate, potentially unlocking hyperpolarized 13C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.

Nantogma S. , de Maissin H. , Adelabu I. , Abdurraheem A. , Nelson C. , Chukanov N.V. , Salnikov O.G. , Koptyug I.V. , Lehmkuhl S. , Schmidt A.B. , Appelt S. , Theis T. , Chekmenev E.Y.
Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate
ACS Sensors. 2024. V.9. N2. P.770–780. DOI: 10.1021/acssensors.3c02075 WOS Scopus РИНЦ AN PMID OpenAlex

Submitted:	Oct 1, 2023
Accepted:	Dec 26, 2023
Published online:	Jan 10, 2024
Published print:	Feb 23, 2024

Web of science:	WOS:001162227200001
Scopus:	2-s2.0-85182566219
Elibrary:	65820151
Chemical Abstracts:	2024:74514
PMID:	38198709
OpenAlex:	W4390692604

DB	Citing
Scopus	3
Web of science	3
Elibrary	2