Perfluorinated Iridium Catalyst for Signal Amplification by Reversible Exchange Provides Metal-Free Aqueous Hyperpolarized [1- 13 C]-Pyruvate
Year: 2023
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Hyperpolarized (HP) carbon-13 [ 13 C] enables the specific investigation of dynamic metabolic and physiologic processes via in vivo MRI-based molecular imaging. As the leading HP metabolic agent, [1- 13 C]pyruvate plays a pivotal role due to its rapid tissue uptake and central role in cellular energetics. Dissolution dynamic nuclear polarization (d-DNP) is considered the gold standard method for the production of HP metabolic probes; however, development of a faster, less expensive technique could accelerate the translation of metabolic imaging via HP MRI to routine clinical use. Signal Amplification by Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) achieves rapid hyperpolarization by using parahydrogen ( p -H 2 ) as the source of nuclear spin order. Currently, SABRE is clinically limited due to the toxicity of the iridium catalyst, which is crucial to the SABRE process. To mitigate Ir contamination, we introduce a novel iteration of the SABRE catalyst, incorporating bis(polyfluoroalkylated) imidazolium salts. This novel perfluorinated SABRE catalyst retained polarization properties while exhibiting an enhanced hydrophobicity. This modification allows the easy removal of the perfluorinated SABRE catalyst from HP [1- 13 C]-pyruvate after polarization in an aqueous solution, using the ReD-SABRE protocol. The residual Ir content after removal was measured via ICP-MS at 177 ppb, which is the lowest reported to date for pyruvate and is sufficiently safe for use in clinical investigations. Further improvement is anticipated once automated processes for delivery and recovery are initiated. SABRE-SHEATH using the perfluorinated SABRE catalyst can become an attractive low-cost alternative to d-DNP to prepare biocompatible HP [1- 13 C]-pyruvate formulations for in vivo applications in next-generation molecular imaging modalities.
DOI: 10.1021/jacs.3c11499
Institutions: National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, Russian Academy of Sciences, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Southern Illinois University Carbondale, National Institute of Neurological Disorders and Stroke, Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Awards: G1273940453, Rapid low-cost production of contrast agents for metabolic imaging, Collaborative Research: Exploiting Spin Networks and Efficient Catalyst/Substrate Separations for NMR "SABRE" Enhancement of Complex Systems, Collaborative Research: Exploiting Spin Networks and Efficient Catalyst/Substrate Separations for NMR "SABRE" Enhancement of Complex Systems, G8940636334
OpenAlex ID: W4390315628