Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions

Josh P Peters; Arne Brahms; Vivian Janicaud; Maria Anikeeva; Eva Peschke; Frowin Ellermann; Arianna Ferrari; Dana Hellmold; Janka Held-Feindt; Na-Mi Kim; Johannes Meiser; Konrad Aden; Rainer Herges; Jan-Bernd Hövener; Andrey N Pravdivtsev

doi:10.1126/sciadv.add3643

Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions

Josh P Peters
, Arne Brahms
, Vivian Janicaud
, Maria Anikeeva
, Eva Peschke
, Frowin Ellermann
, Arianna Ferrari
, Dana Hellmold
, Janka Held-Feindt
, Na-Mi Kim
, Johannes Meiser
, Konrad Aden
, Rainer Herges
, Jan-Bernd Hövener^*
, Andrey N Pravdivtsev^*

^*Corresponding author for this work

Cancer Metabolism Group

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

Abstract

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-15N-NAM and 1-15N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% 15N polarization. We found that the lifetime of hyperpolarized 1-15N-NAM is strongly field- and pH-dependent, with T1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1-15N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15N MRI of 1-15N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.

Original language	English
Article number	eadd3643
Pages (from-to)	eadd3643
Journal	Science advances
Volume	9
Issue number	34
Early online date	23 Aug 2023
DOIs	https://doi.org/10.1126/sciadv.add3643
Publication status	Published - 25 Aug 2023

Keywords

Niacinamide/pharmacology
Nitrogen Isotopes
2-Naphthylamine

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Peters, J. P., Brahms, A., Janicaud, V., Anikeeva, M., Peschke, E., Ellermann, F., Ferrari, A., Hellmold, D., Held-Feindt, J., Kim, N.-M., Meiser, J., Aden, K., Herges, R., Hövener, J.-B., & Pravdivtsev, A. N. (2023). Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions. Science advances, 9(34), eadd3643. Article eadd3643. https://doi.org/10.1126/sciadv.add3643

@article{28b584476ee44bf0a59eda383af9ac44,

title = "Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions",

abstract = "Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-15N-NAM and 1-15N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)\% 15N polarization. We found that the lifetime of hyperpolarized 1-15N-NAM is strongly field- and pH-dependent, with T1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1-15N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15N MRI of 1-15N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.",

keywords = "Niacinamide/pharmacology, Nitrogen Isotopes, 2-Naphthylamine",

author = "Peters, \{Josh P\} and Arne Brahms and Vivian Janicaud and Maria Anikeeva and Eva Peschke and Frowin Ellermann and Arianna Ferrari and Dana Hellmold and Janka Held-Feindt and Na-Mi Kim and Johannes Meiser and Konrad Aden and Rainer Herges and Jan-Bernd H{\"o}vener and Pravdivtsev, \{Andrey N\}",

note = "Funding:We acknowledge funding from German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept(01ZX1915C),DFG (PR1868/3-1,HO-4602/2-2,HO-4602/3,GRK2154-2019,EXC2167,FOR5042, and TRR287)and financial support by Land Schleswig-Holstein with in the funding programme Open Access Publikations fonds. MOIN CC was funded by a grant from the European Regional Development Fund (ERDF) and the Zukunftsprogramm Wirtschaft of Schleswig-Holstein (project no. 122-09-053). A.N.P. acknowledges Kiel University PMI cluster of excellence for intramural support in genzymatic LDH activity studies.J.M. received funding from FNR-INTER(NTER/BMBF/18/13399110).We are also thankful to N. Kiweler and L. Neises from LIH for providing us with K-562cells.",

year = "2023",

month = aug,

day = "25",

doi = "10.1126/sciadv.add3643",

language = "English",

volume = "9",

pages = "eadd3643",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "34",

}

Peters, JP, Brahms, A, Janicaud, V, Anikeeva, M, Peschke, E, Ellermann, F, Ferrari, A, Hellmold, D, Held-Feindt, J, Kim, N-M, Meiser, J, Aden, K, Herges, R, Hövener, J-B & Pravdivtsev, AN 2023, 'Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions', Science advances, vol. 9, no. 34, eadd3643, pp. eadd3643. https://doi.org/10.1126/sciadv.add3643

TY - JOUR

T1 - Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions

AU - Peters, Josh P

AU - Brahms, Arne

AU - Janicaud, Vivian

AU - Anikeeva, Maria

AU - Peschke, Eva

AU - Ellermann, Frowin

AU - Ferrari, Arianna

AU - Hellmold, Dana

AU - Held-Feindt, Janka

AU - Kim, Na-Mi

AU - Meiser, Johannes

AU - Aden, Konrad

AU - Herges, Rainer

AU - Hövener, Jan-Bernd

AU - Pravdivtsev, Andrey N

N1 - Funding:We acknowledge funding from German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept(01ZX1915C),DFG (PR1868/3-1,HO-4602/2-2,HO-4602/3,GRK2154-2019,EXC2167,FOR5042, and TRR287)and financial support by Land Schleswig-Holstein with in the funding programme Open Access Publikations fonds. MOIN CC was funded by a grant from the European Regional Development Fund (ERDF) and the Zukunftsprogramm Wirtschaft of Schleswig-Holstein (project no. 122-09-053). A.N.P. acknowledges Kiel University PMI cluster of excellence for intramural support in genzymatic LDH activity studies.J.M. received funding from FNR-INTER(NTER/BMBF/18/13399110).We are also thankful to N. Kiweler and L. Neises from LIH for providing us with K-562cells.

PY - 2023/8/25

Y1 - 2023/8/25

N2 - Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-15N-NAM and 1-15N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% 15N polarization. We found that the lifetime of hyperpolarized 1-15N-NAM is strongly field- and pH-dependent, with T1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1-15N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15N MRI of 1-15N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.

AB - Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-15N-NAM and 1-15N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% 15N polarization. We found that the lifetime of hyperpolarized 1-15N-NAM is strongly field- and pH-dependent, with T1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1-15N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15N MRI of 1-15N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.

KW - Niacinamide/pharmacology

KW - Nitrogen Isotopes

KW - 2-Naphthylamine

UR - https://www.scopus.com/pages/publications/85168595065

UR - https://pubmed.ncbi.nlm.nih.gov/37611105

U2 - 10.1126/sciadv.add3643

DO - 10.1126/sciadv.add3643

M3 - Article

C2 - 37611105

SN - 2375-2548

VL - 9

SP - eadd3643

JO - Science advances

JF - Science advances

IS - 34

M1 - eadd3643

ER -

Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions

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Keywords

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