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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- C]pyruvate-d for injection in 6 minutes. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1- C]pyruvate-d polarized 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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http://dx.doi.org/10.1002/anie.202306654 | DOI Listing |
Theranostics
April 2025
Division of Medical Physics, Department of Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Killianstr. 5a, Freiburg 79106, Germany.
Metabolic MRI using hyperpolarized (HP) [1-C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at µT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate.
View Article and Find Full Text PDFAnal Chem
March 2025
Chair of Analytical Chemistry and Water Chemistry, School of Natural Sciences, Technical University of Munich, Lichtenbergstr. 4, Garching 85748, Germany.
The ubiquitous use of plastics demands thoughtfulness about their fate in the environment. Biodegradability is, therefore, a prerequisite for the future use of plastics in many applications, including agriculture. Here, we bring forward stable isotope (resonance) Raman microspectroscopy at the single-cell level to broaden the mechanistic understanding of microbial degradation of (micro)plastics in natural systems.
View Article and Find Full Text PDFCommun Chem
October 2024
Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Killianstr. 5a, 79106, Freiburg, Germany.
Hyperpolarized C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-C]acetate and [1-C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P ≈ 28% at 80 mM concentration and P ≈ 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-d at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar).
View Article and Find Full Text PDFAnalyst
October 2024
NMR Signal Enhancement Group, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077 Göttingen, Germany.
Alterations in pH are a hallmark in several pathologies including cancer, ischemia, and inflammation. Non-invasive magnetic resonance methods to measure pH offer a new approach for early diagnosis of diseases characterized by acid-base imbalances. The hyperpolarization with parahydrogen-induced polarization (PHIP) enhances inherently low signals in magnetic resonance experiments by several orders of magnitude and offers a suitable platform to obtain biocompatible markers in less than one minute.
View Article and Find Full Text PDFChemistry
September 2024
NMR Signal Enhancement Group Max Planck Institute for Multidisciplinary Sciences, Am Faßberg 11, 37077, Göttingen, Germany.
Parahydrogen-induced polarization (PHIP) is an emerging technique to enhance the signal of stable isotope metabolic contrast agents for Magnetic Resonance (MR). The objective of this study is to continue establishing 1-C-pyruvate-d, signal-enhanced via PHIP, as a hyperpolarized contrast agent, obtained in seconds, to monitor metabolism in human cancer. Our focus was on human pancreatic and colon tumor xenografts.
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