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1. Scalable Hyperpolarized MRI Enabled by Ace‐SABRE of [1‐ ¹³ C]Pyruvate

   https://doi.org/10.1002/anie.202501231  

   McBride, Stephen J; Pike, Megan; Curran, Erica; Zavriyev, Alexander; Adebesin, Bukola; Tucker, Luke; Harzan, Jared M; Senanayake, Ishani M; Abdulmojeed, Mustapha; Theiss, Franziska; et al (August 2025, Angewandte Chemie International Edition)

   Abstract Hyperpolarized (HP) MRI using [1–¹³C]pyruvate is emerging as a promising molecular imaging approach. Among hyperpolarization methods, Signal Amplification By Reversible Exchange (SABRE) is attractive because SABRE polarizes the substrates directly in room‐temperature solutions avoiding complex hardware. Most SABRE experiments have historically been performed in methanol, a relatively toxic and difficult‐to‐remove solvent. Here we demonstrate the use of a 80/20 acetone/water (A/W) solvent system (Ace‐SABRE) to provide hyperpolarized [1–¹³C]pyruvate with up to 17% polarization, then implement a solvent processing protocol to achieve injectable solutions retaining 74% of the initial polarization, and lastly we demonstrate HP in vivo spectroscopy and imaging using the Ace‐SABRE platform to showcase metabolic tracking in a hepatocellular carcinoma (HCC) tumor as well as HP‐MRI, both in direct comparison to dissolution dynamic nuclear polarization (d‐DNP) experiments. The Ace‐SABRE technique promises faster adoption of SABRE hyperpolarization in biological experiments, overall lowering the barriers to entry for HP‐NMR and HP‐MRI. 

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2. In Vivo Metabolic Imaging of [1‐ ¹³ C]Pyruvate‐d ₃ Hyperpolarized By Reversible Exchange With Parahydrogen**

   https://doi.org/10.1002/anie.202306654  

   de_Maissin, Henri; Groß, Philipp R; Mohiuddin, Obaid; Weigt, Moritz; Nagel, Luca; Herzog, Marvin; Wang, Zirun; Willing, Robert; Reichardt, Wilfried; Pichotka, Martin; et al (September 2023, Angewandte Chemie International Edition)

   Abstract Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non‐invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra‐fast and low‐cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1‐¹³C]pyruvate‐d₃for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐¹³C]pyruvate‐d₃polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms. 

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3. In vivo Metabolic Sensing of Hyperpolarized [1‐ ¹³ C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst

   https://doi.org/10.1002/anie.202407349  

   Ettedgui, Jessica; Yamamoto, Kazutoshi; Blackman, Burchelle; Koyasu, Norikazu; Raju, Natarajan; Vasalatiy, Olga; Merkle, Hellmut; Chekmenev, Eduard Y; Goodson, Boyd M; Krishna, Murali C; et al (July 2024, Angewandte Chemie International Edition)

   Abstract Real‐time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non‐invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost‐effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 1.2‐fold increase in [1‐¹³C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy‐metal‐containing catalyst from the hyperpolarized [1‐¹³C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE‐SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3‐fold decrease in hyperpolarization potency. This proof‐of‐concept study encourages wider adoption of SABRE hyperpolarized [1‐¹³C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases. 

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4. Over four minutes of pyruvate T1 using chemically and physically induced deceleration of relaxation

   https://doi.org/10.1038/s41467-026-73214-w  

   Peters, Josh P; Teleanu, Florin; Zou, Huijing; Rasool, Ehtisham; Haj_Mohamad, Farhad; Schäfer, Heiner; Hövener, Jan-Bernd; Jerschow, Alexej; Pravdivtsev, Andrey N (December 2026, Nature Communications)

   Abstract [1-¹³C]pyruvate is the most widely used probe for hyperpolarized metabolic magnetic resonance imaging, with profound applications in tumor and inflammation diagnosis as well as treatment monitoring. The most fundamental hurdle to broader application, however, remains the rapid relaxation of polarization and the associated signal loss. Here, we report a method to address this challenge. Studying the nuclear spin relaxation dispersion of [1-¹³C]pyruvate across magnetic fields from 8 μT to 9.4 T, as a function of additives, solvents, and preparation methods, allows us to achieveT₁relaxation times of up to four minutes. Such a longT₁could enable reliable quality control and nearly polarization loss-free transport, further boosting the power of hyperpolarized metabolic MRI. The power of the optimized protocol forT₁elongation in vitro is showcased by more than doubling the sensitivity in a metabolic experiment. 

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5. Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer

   https://doi.org/10.1038/s42004-024-01316-x  

   Mohiuddin, Obaid; de_Maissin, Henri; Pravdivtsev, Andrey N; Brahms, Arne; Herzog, Marvin; Schröder, Leif; Chekmenev, Eduard Y; Herges, Rainer; Hövener, Jan-Bernd; Zaitsev, Maxim; et al (December 2024, Communications Chemistry)

   Abstract Hyperpolarized¹³C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high¹³C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-¹³C]acetate and [1-¹³C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized toP_13C ≈ 28% at 80 mM concentration andP_13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d₆at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where¹³C MRI is performed. We exemplified the utility of the design with sub-second in situ¹³C MRI of ethyl [1-¹³C]pyruvate-d₆. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid¹³C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized¹³C MRI. 

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