Our Research & Other Key Publications

A. N. Pravdivtsev, A. Brahms, S. Kienitz, F. D. Sönnichsen, J.-B. Hövener, R. Herges, ChemPhysChem 2021, 22, 370-377.

DOI: 10.1002/cphc.202000957

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cphc.202000957

A novel tracer was synthesized to investigate the influence of multiple unsaturated compounds on hyperpolarization. Using hyperpolarization, previously hidden processes at the catalyst were made visible. This highlights the technology's potential for catalyst optimization.

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A. B. Schmidt, A. Brahms, F. Ellermann, S. Knecht, S. Berner, J. Henning, D. von Elverfeldt, R. Herges, J.-B. Hövener, A. N. Pravdivtsev, Phys. Chem. Chem. Phys. 2021, 23, 26645-26652.

DOI: 10.1039/D1CP04153C

https://pubs.rsc.org/en/content/articlelanding/2021/cp/d1cp04153c

A newly developed pulse sequence improved the theoretically achievable polarization of our tracer to 99.6 % while the non-deuterated form has its theoretical maximum at 19.2 % polarization. These findings clearly demonstrate the critical importance of deuteration and directly underscore the superiority of our deuterated tracer over its non-deuterated form.

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A. N. Pravdivtsev, A. Brahms, F. Ellermann, T. Stamp, R. Herges, J.-B. Hövener, Sci. Rep. 2022, 12, 19361.

DOI: 10.1038/s41598-022-22347-1

https://www.nature.com/articles/s41598-022-22347-1

PHIP+ allows for significantly higher production rates of hyperpolarized pyruvate compared to d-DNP, with a theoretical polarization level of 100 % for our tracer. The polarization time of our substance was reduced to just 7 seconds while d-DNP requires approximately 2 hours for similar results. This work highlights the tremendous potential of the PHIP+ technique as a superior alternative to the already established d-DNP method.

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A. Brahms, A. N. Pravdivtsev, T. Stamp, F. Ellermann, F. D. Sönnichsen, J.-B. Hövener, R. Herges, Chem. Eur. J. 2022, 28, e202201210.

DOI: 10.1002/chem.202201210

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202201210

In this work, our tracer was synthesized for the first time using a newly developed synthesis demonstrating superior yields compared to all existing methods. Furthermore, the tracer was successfully produced in a wide variety of isotopic enrichments. This publication lays the foundation for hyperpolarized pyruvate based on our tracer molecule.

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F. Ellermann, A. Sirbu, A. Brahms, C. Assaf, R. Herges, J.-B. Höevner, A. N. Pravdivtsev, Nat. Commun. 2023, 14, 4774.

DOI: 10.1038/s41467-023-40539-9

https://www.nature.com/articles/s41467-023-40539-9

In this key publication, an automated PHIP polarizer was developed and successfully tested using our tracer compound. We were able to fully automate smaple filling, hyperpolarization, quantification, and transfer to a mobile 0.5 T MRI scanner, allowing 60 consecutive measurements without operator intervention. This approach demonstrates the effectiveness and capability of PHIP+.

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A. Brahms, A. N. Pravdivtsev, L. Thorns, F. D. Sönnichsen, J.-B. Hövener, R. Herges, J. Org. Chem. 2023, 88, 15018-15028.

DOI: 10.1021/acs.joc.3c01461

https://pubs.acs.org/doi/10.1021/acs.joc.3c01461

Building on further investigation and optimization of our synthesis, the process was successfully scaled up, significantly improving the economic viability of tracer production. Our synthesis achieves nearly 20 times higher yields compared to existing methods. This work represents an important advancement in making our tracer compound more accessible for braoder applications and is considered our key publication.

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O. Mohiuddin, H. de Maissin, A. N. Pravdivtsev, A. Brahms, M. Herzog, L. Schröder, E. Y. Chekmenev, R. Herges, J.-B. Hövener, M. Zaitsev, D. von Elverfeldt, A. B. Schmidt, Commun. Chem. 2024, 7, 240.

DOI: 10.1038/s42004-024-01316-x

https://www.nature.com/articles/s42004-024-01316-x

This work demonstrates that hyperpolarized contrast agents based on the PHIP-SAH approach can be produced directly inside the bore of an MRI scanner, without any external polarizer. Polarization was achieved in under 10 seconds, underlining the speed and simplicity of this hyperpolarization route for future point-of-care applications.

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K. Them, F. Ellermann, A. N. Pravdivtsev, O. G. Salnikov, I. V. Skovpin, I. V. Koptyug, R. Herges, J.-B. Hövener, J. Am. Chem. Soc. 2021, 143, 13694-13700.

DOI: 10.1021/jacs.1c05254

https://pubs.acs.org/doi/10.1021/jacs.1c05254

This work introduces a new hyperpolarization route in which polarization generated by parahydrogen is relayed to target molecules via proton exchange rather than direct hydrogenation. While conceptually distinct from our PHIP+ approach, it broadens the toolbox of parahydrogen-based hyperpolarization methods within our research network.

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J. P. Peters, A. Brahms, V. Janicaud, M. Anikeeva, E. Peschke, F. Ellermann, A. Ferrari, D. Hellmold, J. Held-Feindt, N.-m. Kim, J. Meiser, K. Aden, R. Herges, J.-B. Hövener, A. N. Pravdivtsev, Sci. Adv. 2023, 9, eadd3643.

DOI: 10.1126/sciadv.add3643

https://www.science.org/doi/10.1126/sciadv.add3643

This work explores nicotinamide as a new hyperpolarized tracer for metabolic imaging, using dissolution DNP rather than PHIP to achieve nitrogen-15 polarization. It demonstrates our team's broader expertise in developing and characterizing new hyperpolarized tracer molecules beyond pyruvate.

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C. D. Assaf, X. Gui, O. G. Salnikov, A. Brahms, N. V. Chukanov, I. V. Skovpin, E. Y. Chekmenev, R. Herges, S. B. Duckett, I. V. Koptyug, K. Buckenmaier, R. Körber, M. Plaumann, A. A. Auer, J.-B. Hövener, A. N. Pravdivtsev, Commun. Chem. 2024, 7, 286.

DOI: 10.1038/s42004-024-01376-z

https://www.nature.com/articles/s42004-024-01376-z

This work introduces a new NMR method to precisely quantify ligand exchange rates at the catalyst center used in SABRE-based hyperpolarization. While SABRE is a different hyperpolarization approach to our PHIP+ technology, the underlying mechanistic insights contribute to our team's overall expertise in catalyst behaviour during hyperpolarization.

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J. P. Peters, C. Assaf, A. Brahms, K. Them, M. Gerdsen, R. Herges, J.-B. Hövener, A. N. Pravdivtsev, Sci. Adv. 2025, 11, eadx2316.

DOI: 10.1126/sciadv.adx2316

https://www.science.org/doi/10.1126/sciadv.adx2316

This work describes a newly discovered effect, CIDER (also patented), in which simple biocompatible additives substantially slow the decay of hyperpolarization in solution. This is highly relevant for preserving signal during the transfer of hyperpolarized tracers from the polarizer to the MARI scanner, directly supporting the practical use of our pyruvate-based contrast agent.

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S. Punwani, P. E. Z. Larson, C. Laustsen, J. VanderMeulen, J. H. Ardenkjær-Larsen, A. W. Autry, J. A. Bankson, J. Bernard, R. Bok, L. B. Bertelsen, J. Che, A. P. Chen, R. Chowdhury, A. Comment, C. H. Cunningham, D. Dang, F. A. Gallagher, A. Gaunt, Y. Gong, J. W. Gordon, A. Grimmer, J. Grist, E. S. S. Hansen, M. H. Lerche, R. L. Hesketh, J.-B. Hoevener, C.-Y. Hsieh, K. R. Keshari, S. Kozerke, T. Lanz, D. Mayer, M. McLean, J. M. Park, J. Slater, D. Tyler, J.-L. Vanderheyden, C. von Morze, F. Zaccagna, V. Zaha, D. Xu, D. Vigneron, Magn. Reson. Med. 2025, 94, 1386-1400.

DOI: 10.1002/mrm.30570

https://onlinelibrary.wiley.com/doi/10.1002/mrm.30570

This consensus paper, endorsed by the ISMRM Hyperpolarized MR Study Group, establishes best-practice recommendations for conducting multi-center human studies with hyperpolarized [1-¹³C]pyruvate MRI. It provides important guidance for the clinical translation pathway that our own hyperpolarized pyruvate tracer will eventually need to follow.

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J.-B. Hövener, A. N. Pravdivtsev, B. Kidd, C. R. Bowers, S. Glöggler, K. V. Kovtunov, M. Plaumann, R. Katz-Brull, K. Buckenmaier, A. Jerschow, F. Reineri, T. Theis, R. V. Shchepin, S. Wagner, P. Bhattacharya, N. M. Zacharias, E. Y. Chekmenev, Angew. Chem. Int. Ed. 2018, 57, 11140-11162.

DOI: 10.1002/anie.201711842

https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201711842

This widely cited review provides a comprehensive overview of parahydrogen-based hyperpolarization techniques and their biomedical applications. It serves as a key reference work establishing the scientific foundation on which our PHIP+ technology builds.

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F. Reineri, T. Boi, S. Aime, Nat. Commun. 2015, 6, 5858.

DOI: 10.1038/ncomms6858

https://www.nature.com/articles/ncomms6858#citeas

This pioneering work first demonstrated that ¹³C-carboxylate signals of acetate and pyruvate can be hyperpolarized via side-arm hydrogenation with parahydrogen (PHIP-SAH). It laid the conceptual groundwork for our own PHIP+ technology and the synthesis of our vinyl pyruvate tracer.

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O. G. Salnikov, N. V. Chukanov, A. N. Pravdivtsev, D. B. Burueva, S. V. Sviyazov, K. Them, J.-B. Hövener, I. V. Koptyug, ChemPhysChem 2025, 26, e202401119.

DOI: 10.1002/cphc.202401119

https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cphc.202401119

This recent review summarizes the state of the art in PHIP-SAH methodology and its preclinical applications for diagnosing diseases such as cancer. It provides excellent field overview that situates our own PHIP+ technology within the broader landscape of parahydrogen-based hyperpolarization research.

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