In Vivo Imaging of Tumor Metabolic Heterogeneity Using [1-13C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen
Motivation: Hyperpolarized [1-13C]pyruvate MRI is promising for studying cancer metabolism and assessing early therapy response but requires high-throughput and less complex hyperpolarization techniques for wide availability. Goal(s): Demonstrating metabolic imaging in a genetic mouse model of metastasizing breast cancer (MMTV-PyMT) using purified [1-13C]-pyruvate-d3 hyperpolarized via parahydrogen-based Signal Amplification By Reversible Exchange (SABRE). Approach: Our rapid (6 min) and efficient hyperpolarization method yielded highly-polarized (>10%) [1-13C]-pyruvate-d3 in safe aqueous solutions. Results: Administered to two PyMT-mice, 13C chemical shift imaging detected the injected pyruvate and metabolized [1-13C]-lactate. Analysis revealed elevated lactate levels in tumors compared to healthy breast tissue, highlighting tumor compartments with distinct metabolic profiles. Impact: We showcase our rapid, cost-effective SABRE hyperpolarization approach, yielding safe, highly-polarized pyruvate for inaugural cancer metabolic investigations. This innovation expands high-throughput preclinical HP-MRI research, enabling comprehensive exploration of tumor biology, metabolic processes, and therapeutic responses in cancer.
Authors
- Christoph Müller (ORCID: https://orcid.org/0000-0002-8187-9170)
- Andreas Benjamin Schmidt (ORCID: https://orcid.org/0000-0001-8944-7463)
- Lisa Heß
- André F. Martins (ORCID: https://orcid.org/0000-0002-0171-0261)
- Michael Bock (ORCID: https://orcid.org/0000-0001-9720-3506)
- Nicole Klemm
- Julia Mitschke
- Jan‐Bernd Hövener (ORCID: https://orcid.org/0000-0001-7255-7252)
- Maxim Zaitsev (ORCID: https://orcid.org/0000-0001-7530-1228)
- Luca Nagel (ORCID: https://orcid.org/0000-0002-5530-6264)
- Dominik von Elverfeldt (ORCID: https://orcid.org/0000-0002-6219-3528)
- Philipp R. Groß (ORCID: https://orcid.org/0009-0003-5044-3109)
- Thomas Reinheckel (ORCID: https://orcid.org/0000-0001-9866-9105)
- Franz Schilling (ORCID: https://orcid.org/0000-0001-5239-4628)
- Stephan Knecht (ORCID: https://orcid.org/0000-0002-8487-4324)
- Robert Willing (ORCID: https://orcid.org/0009-0003-8190-5345)
- Eduard Y. Chekmenev (ORCID: https://orcid.org/0000-0002-8745-8801)
- Moritz Weigt (ORCID: https://orcid.org/0009-0007-6228-8600)
- Stefan Petersen (ORCID: https://orcid.org/0009-0009-3893-4101)
Publication Details
- Journal
- Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
- Published
- 2024-11-26
- DOI
- https://doi.org/10.58530/2024/5080
- Primary Topic
- Advanced NMR Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00