Article
Chemistry, Applied
O. Bondar, E. Cavallari, C. Carrera, S. Aime, F. Reineri
Summary: ParaHydrogen Induced Polarization-Side Arm Hydrogenation (PHIP-SAH) is an inexpensive tool for obtaining hyperpolarized pyruvate for in vivo diagnostics. The solvent used in the hydrogenation process can affect efficiency and hyperpolarization level. Coordinating solvents can significantly increase efficiency or hyperpolarization level, but may not be compatible with metabolic applications. The extraction of hyperpolarized product in an aqueous solution can improve biocompatibility by removing traces of organic solvents.
Article
Chemistry, Physical
Alastair Marshall, Alon Salhov, Martin Gierse, Christoph Mueller, Michael Keim, Sebastian Lucas, Anna Parker, Jochen Scheuer, Christophoros Vassiliou, Philipp Neumann, Fedor Jelezko, Alex Retzker, John W. Blanchard, Ilai Schwartz, Stephan Knecht
Summary: We present a technique for transferring parahydrogen-derived singlet order into 13C magnetization using adiabatic radio frequency sweeps at microtesla fields, enabling real-time monitoring of processes within the body. By avoiding relaxation induced by strongly coupled quadrupolar nuclei, significant improvements in achievable polarization, reaching above 60% nuclear spin polarization, are demonstrated for several molecules relevant in metabolic imaging. Furthermore, a site-selective deuteration scheme is introduced to enhance the efficiency of the polarization transfer.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Physical
Theresa Hune, Salvatore Mamone, Henning Schroeder, Anil P. Jagtap, Sonja Sternkopf, Gabriele Stevanato, Sergey Korchak, Claudia Fokken, Christoph A. Mueller, Andreas B. Schmidt, Dorothea Becker, Stefan Gloeggler
Summary: The metabolism of malignant cells can be imaged using signal-enhanced 1-C-13-pyruvate-d3, which is rapidly enhanced via para-hydrogen. This study demonstrates the feasibility of metabolic tumor imaging by monitoring the conversion of pyruvate into lactate and its kinetics, providing a potential method for rapidly detecting and monitoring changes in tumor metabolism.
Article
Chemistry, Multidisciplinary
Salvatore Mamone, Anil P. Jagtap, Sergey Korchak, Yonghong Ding, Sonja Sternkopf, Stefan Gloeggler
Summary: Hyperpolarization methods in magnetic resonance enhance signals for real-time investigation of dynamic processes. In this study, a novel pulsed method based on para-hydrogen is proposed to rapidly hyperpolarize C-13-labeled substrates. The method is successfully demonstrated in monitoring metabolic processes in cancer cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Francesca Reineri, Eleonora Cavallari, Carla Carrera, Silvio Aime
Summary: ParaHydrogen induced polarization (PHIP) is an efficient and cost-effective hyperpolarization method, but faces challenges in biological investigations due to chemical limitations. Recent advancements in hydrogenative PHIP (h-PHIP) have expanded the possibilities of hyperpolarizing metabolites, offering new opportunities for biological applications.
MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Physical
Isaiah Adelabu, Patrick TomHon, Mohammad S. H. Kabir, Shiraz Nantogma, Mustapha Abdulmojeed, Iuliia Mandzhieva, Jessica Ettedgui, Rolf E. Swenson, Murali C. Krishna, Thomas Theis, Boyd M. Goodson, Eduard Y. Chekmenev
Summary: Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) was investigated for rapid hyperpolarization of C-13(1) spins of [1-C-13]pyruvate using parahydrogen. The exchange of pyruvate with an iridium polarization transfer complex can be modulated by temperature and co-ligation conditions. Efficient C-13 polarization was achieved in less than 30 seconds by restricting the chemical exchange of [1-C-13]pyruvate at lower temperatures, with the possibility of fast release for future biomedical applications.
Article
Chemistry, Physical
Carla Carrera, Eleonora Cavallari, Giuseppe Digilio, Oksana Bondar, Silvio Aime, Francesca Reineri
Summary: An efficient synthesis of vinyl-[1-C-13]pyruvate and its application in hyperpolarization reactions have been reported, showing that ethyl-ester is more efficient compared to allyl-ester. A high-concentration aqueous solution of the product meeting the requirements for biological applications has been obtained, and in vitro metabolic transformation has been observed.
Article
Chemistry, Multidisciplinary
Henri de Maissin, Philipp R. Gross, Obaid Mohiuddin, Moritz Weigt, Luca Nagel, Marvin Herzog, Zirun Wang, Robert Willing, Wilfried Reichardt, Martin Pichotka, Lisa Hess, Thomas Reinheckel, Henning J. Jessen, Robert Zeiser, Michael Bock, Dominik von Elverfeldt, Maxim Zaitsev, Sergey Korchak, Stefan Gloeggler, Jan-Bernd Hoevener, Eduard Y. Chekmenev, Franz Schilling, Stephan Knecht, Andreas B. Schmidt
Summary: Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is a non-invasive technique for diagnosing, staging, and monitoring response to treatment in various diseases. The Signal Amplification By Reversible Exchange (SABRE) method provides a fast and low-cost way to produce HP pyruvate. In this study, a novel routine to produce aqueous HP [1-C-13]pyruvate-d(3) for injection in 6 minutes was demonstrated, making HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Andreas B. Schmidt, Henri de Maissin, Isaiah Adelabu, Shiraz Nantogma, Jessica Ettedgui, Patrick TomHon, Boyd M. Goodson, Thomas Theis, Eduard Y. Chekmenev
Summary: Despite successes in oncology, patient outcomes are often disappointing. Diagnostic imaging is shifting towards functional imaging of pathology for better understanding of individual disease biology and personalized therapies. This study presents a fast and low-cost hyperpolarization method using chemical exchange with parahydrogen, allowing for the cost-effective production of hyperpolarized [1-13C]pyruvate biosensors with great potential for in vivo applications.
Article
Chemistry, Multidisciplinary
Baptiste Joalland, Thomas Theis, Stephan Appelt, Eduard Y. Chekmenev
Summary: This study demonstrates the utility of Radiofrequency Amplification by Stimulated Emission Radiation (RASER) for background-free proton detection of hyperpolarized biomolecules in a clinically relevant magnetic field. The results show that RASER detection without radio-frequency excitation could pave the way to new applications in high-resolution NMR spectroscopy and in vivo spectroscopy and imaging.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Kai-Oliver Brenske, Meike Emondts, Sven T. Hoernig, Sinan Panitz, Maria I. Pieper, Aron Ligori, Alexander Schacht, Johanna Henkel, Juergen Klankermayer, Andreas Herrmann
Summary: Enhancing the NMR signals of biomacromolecules by hyperpolarization is challenging due to the requirement of specific catalytic interactions and the large size and insolubility of the biomolecules. In this study, we achieved unprecedented hyperpolarization of the cancer-targeting DNA aptamer AS1411 by screening different molecular motifs and adjusting the polarity of AS1411. The results have the potential to advance hyperpolarized molecular imaging technology for disease detection.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Jacob R. Lindale, Shannon L. Eriksson, Warren S. Warren
Summary: Hyperpolarization methods in magnetic resonance, such as SABRE and X-SABRE, have the potential to generate large polarizations on multiple targets at high magnetic fields. However, previous methods have been limited to selectively hyperpolarizing single targets. In this study, a new pulse sequence-based approach is introduced, allowing for broadband excitation of SABRE hyperpolarization at high fields, which enables simultaneous hyperpolarization of multiple targets.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
J. Eills, E. Cavallari, R. Kircher, G. Di Matteo, C. Carrera, L. Dagys, M. H. Levitt, K. L. Ivanov, S. Aime, F. Reineri, K. Muennemann, D. Budker, G. Buntkowsky, S. Knecht
Summary: This study introduces a novel H-1 imaging method in which hyperpolarized spin order is released for imaging through a specific biochemical reaction, while suppressing background signals from water. It allows for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jasmine Y. Hu, Sana Vaziri, Nikolaj Bogh, Yaewon Kim, Adam W. Autry, Robert A. Bok, Yan Li, Christoffer Laustsen, Duan Xu, Peder E. Z. Larson, Susan Chang, Daniel B. Vigneron, Jeremy W. Gordon
Summary: This study aimed to investigate the use of high-resolution hyperpolarized C-13 pyruvate MRI for measuring cerebral perfusion in the human brain. HP pyruvate MRI images were acquired and perfusion parameters were calculated and compared to arterial spin labeling results. The study found that high-resolution pyruvate images can provide measures of cerebral perfusion that are positively correlated to ASL perfusion values, indicating the potential of hyperpolarized pyruvate MRI for assessing cerebral metabolism and perfusion within the same study.
MAGNETIC RESONANCE IN MEDICINE
(2023)
Article
Chemistry, Analytical
Oleg G. Salnikov, Ivan A. Trofimov, Andrey N. Pravdivtsev, Kolja Them, Jan-Bernd Hoevener, Eduard Y. Chekmenev, Igor V. Koptyug
Summary: This research demonstrates the utility of using RASER to amplify nuclear magnetic resonance (NMR) signals of solute and solvent molecules in the liquid state. The study shows that parahydrogen-induced RASER can enhance nuclear spin polarization of protons and heteronuclei in a wide range of molecules. The experimental results are supported by control experiments and spin dynamics simulations. The enhanced NMR sensitivity achieved through RASER can have significant applications in mixture analysis, metabolomics, and structure determination.
ANALYTICAL CHEMISTRY
(2022)