Parahydrogen-Polarized [1-13C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

Luca Nagel; Martin Gierse; Wolfgang Gottwald; Zumrud Ahmadova; Martin Grashei; Pascal Wolff; Felix Josten; Senay Karaali; Christoph A. Müller; Sebastian Lucas; Jochen Scheuer; Christoph Müller; John Blanchard; Geoffrey J. Topping; Andre Wendlinger; Nadine Setzer; Sandra Sühnel; Jonas Handwerker; Christophoros Vassiliou; Frits H.A. van Heijster; Stephan Knecht; Michael Keim; Franz Schilling; Ilai Schwartz

doi:10.1002/advs.202303441

Parahydrogen-Polarized [1-¹³C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

Luca Nagel, Martin Gierse, Wolfgang Gottwald, Zumrud Ahmadova, Martin Grashei, Pascal Wolff, Felix Josten, Senay Karaali, Christoph A. Müller, Sebastian Lucas, Jochen Scheuer, Christoph Müller, John Blanchard, Geoffrey J. Topping, Andre Wendlinger, Nadine Setzer, Sandra Sühnel, Jonas Handwerker, Christophoros Vassiliou, Frits H.A. van HeijsterStephan Knecht, Michael Keim, Franz Schilling, Ilai Schwartz

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Abstract

Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-¹³C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70–160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

Original language	English
Article number	2303441
Journal	Advanced Science
Volume	10
Issue number	30
DOIs	https://doi.org/10.1002/advs.202303441
State	Published - 26 Oct 2023

Keywords

hyperpolarization
magnetic resonance imaging (MRI)
metabolic imaging
parahydrogen
pyruvate

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Nagel, L., Gierse, M., Gottwald, W., Ahmadova, Z., Grashei, M., Wolff, P., Josten, F., Karaali, S., Müller, C. A., Lucas, S., Scheuer, J., Müller, C., Blanchard, J., Topping, G. J., Wendlinger, A., Setzer, N., Sühnel, S., Handwerker, J., Vassiliou, C., ... Schwartz, I. (2023). Parahydrogen-Polarized [1-¹³C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging. Advanced Science, 10(30), Article 2303441. https://doi.org/10.1002/advs.202303441

@article{81e1222768a042839787330408d120f4,

title = "Parahydrogen-Polarized [1-13C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging",

abstract = "Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70–160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.",

keywords = "hyperpolarization, magnetic resonance imaging (MRI), metabolic imaging, parahydrogen, pyruvate",

author = "Luca Nagel and Martin Gierse and Wolfgang Gottwald and Zumrud Ahmadova and Martin Grashei and Pascal Wolff and Felix Josten and Senay Karaali and M{\"u}ller, {Christoph A.} and Sebastian Lucas and Jochen Scheuer and Christoph M{\"u}ller and John Blanchard and Topping, {Geoffrey J.} and Andre Wendlinger and Nadine Setzer and Sandra S{\"u}hnel and Jonas Handwerker and Christophoros Vassiliou and {van Heijster}, {Frits H.A.} and Stephan Knecht and Michael Keim and Franz Schilling and Ilai Schwartz",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.",

year = "2023",

month = oct,

day = "26",

doi = "10.1002/advs.202303441",

language = "English",

volume = "10",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "Wiley-VCH Verlag",

number = "30",

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Nagel, L, Gierse, M, Gottwald, W, Ahmadova, Z, Grashei, M, Wolff, P, Josten, F, Karaali, S, Müller, CA, Lucas, S, Scheuer, J, Müller, C, Blanchard, J, Topping, GJ, Wendlinger, A, Setzer, N, Sühnel, S, Handwerker, J, Vassiliou, C, van Heijster, FHA, Knecht, S, Keim, M, Schilling, F & Schwartz, I 2023, 'Parahydrogen-Polarized [1-¹³C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging', Advanced Science, vol. 10, no. 30, 2303441. https://doi.org/10.1002/advs.202303441

TY - JOUR

T1 - Parahydrogen-Polarized [1-13C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

AU - Nagel, Luca

AU - Gierse, Martin

AU - Gottwald, Wolfgang

AU - Ahmadova, Zumrud

AU - Grashei, Martin

AU - Wolff, Pascal

AU - Josten, Felix

AU - Karaali, Senay

AU - Müller, Christoph A.

AU - Lucas, Sebastian

AU - Scheuer, Jochen

AU - Müller, Christoph

AU - Blanchard, John

AU - Topping, Geoffrey J.

AU - Wendlinger, Andre

AU - Setzer, Nadine

AU - Sühnel, Sandra

AU - Handwerker, Jonas

AU - Vassiliou, Christophoros

AU - van Heijster, Frits H.A.

AU - Knecht, Stephan

AU - Keim, Michael

AU - Schilling, Franz

AU - Schwartz, Ilai

PY - 2023/10/26

Y1 - 2023/10/26

N2 - Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70–160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

AB - Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70–160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

KW - hyperpolarization

KW - magnetic resonance imaging (MRI)

KW - metabolic imaging

KW - parahydrogen

KW - pyruvate

UR - http://www.scopus.com/inward/record.url?scp=85168093934&partnerID=8YFLogxK

U2 - 10.1002/advs.202303441

DO - 10.1002/advs.202303441

M3 - Article

C2 - 37587776

AN - SCOPUS:85168093934

SN - 2198-3844

VL - 10

JO - Advanced Science

JF - Advanced Science

IS - 30

M1 - 2303441

ER -

Parahydrogen-Polarized [1-¹³C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

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