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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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In vivo Metabolic Sensing of Hyperpolarized [1‐ 13 C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst
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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- PAR ID:
- 10547209
- Publisher / Repository:
- Wiley-VCH
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/anie.202407349
