Parahydrogen-Polarized 1-13 CPyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

• Published in: Advanced science 2023-10, Vol.10 (30), p.e2303441
• Main Authors: Nagel, Luca, Gierse, Martin, Gottwald, Wolfgang, Ahmadova, Zumrud, Grashei, Martin, Wolff, Pascal, Josten, Felix, Karaali, Senay, Müller, Christoph A, Lucas, Sebastian, Scheuer, Jochen, Müller, Christoph, Blanchard, John, Topping, Geoffrey J, Wendlinger, Andre, Setzer, Nadine, Sühnel, Sandra, Handwerker, Jonas, Vassiliou, Christophoros, van Heijster, Frits H A, Knecht, Stephan, Keim, Michael, Schilling, Franz, Schwartz, Ilai
• Format: Article
• Language: English
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202303441

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 [1-13 C]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.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 [1-13 C]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.