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Article

pH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging

Department of Nuclear Medicine, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich, Germany
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Academic Editors: Andre F. Martins and Mark Pagel
Pharmaceuticals 2021, 14(4), 327; https://doi.org/10.3390/ph14040327
Received: 26 February 2021 / Revised: 22 March 2021 / Accepted: 30 March 2021 / Published: 2 April 2021
(This article belongs to the Special Issue Next Generation of MRI Agents)
Hyperpolarized 13C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time T2. In this context, local T2-changes might introduce a quantification bias to imaging biomarkers. Here, we investigated the pH dependence of the apparent transverse relaxation time constant (denoted here as T2) of six 13C-labelled molecules. We obtained minimum and maximum T2 values within pH 1–13 at 14.1 T: [1-13C]acetate (T2,min = 2.1 s; T2,max = 27.7 s), [1-13C]alanine (T2,min = 0.6 s; T2,max = 10.6 s), [1,4-13C2]fumarate (T2,min = 3.0 s; T2,max = 18.9 s), [1-13C]lactate (T2,min = 0.7 s; T2,max = 12.6 s), [1-13C]pyruvate (T2,min = 0.1 s; T2,max = 18.7 s) and 13C-urea (T2,min = 0.1 s; T2,max = 0.1 s). At 7 T, T2-variation in the physiological pH range (pH 6.8–7.8) was highest for [1-13C]pyruvate (ΔT2 = 0.95 s/0.1pH) and [1-13C]acetate (ΔT2 = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused T2 variations of up to 45.4% for [1-13C]acetate and 23.6% for [1-13C]pyruvate. For [1-13C]acetate, spatially resolved pH measurements using T2-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of T2 suggests that pH alterations potentially influence signal strength for hyperpolarized 13C-acquisitions. View Full-Text
Keywords: T2 relaxation time constant; pH; [1-13C]pyruvate; [1-13C]acetate; 13C-labeled biomolecules; hyperpolarization; hyperpolarized MRI; magnetic resonance spectroscopy T2 relaxation time constant; pH; [1-13C]pyruvate; [1-13C]acetate; 13C-labeled biomolecules; hyperpolarization; hyperpolarized MRI; magnetic resonance spectroscopy
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MDPI and ACS Style

Grashei, M.; Hundshammer, C.; van Heijster, F.H.A.; Topping, G.J.; Schilling, F. pH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging. Pharmaceuticals 2021, 14, 327. https://doi.org/10.3390/ph14040327

AMA Style

Grashei M, Hundshammer C, van Heijster FHA, Topping GJ, Schilling F. pH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging. Pharmaceuticals. 2021; 14(4):327. https://doi.org/10.3390/ph14040327

Chicago/Turabian Style

Grashei, Martin, Christian Hundshammer, Frits H.A. van Heijster, Geoffrey J. Topping, and Franz Schilling. 2021. "pH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging" Pharmaceuticals 14, no. 4: 327. https://doi.org/10.3390/ph14040327

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