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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. 

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.