Abstract
Magnetic Resonance Imaging combined with hyperpolarized 13C-labelled metabolic contrast agents produced via dissolution Dynamic Nuclear Polarization can, non-invasively and in real-time, report on tissue specific aberrant metabolism. However, hyperpolarization equipment is expensive, technically demanding and needs to be installed on-site for the end-user. In this work, we provide a robust methodology that allows remote production of the hyperpolarized 13C-labelled metabolic contrast agents. The methodology, built on photo-induced thermally labile radicals, allows solid sample extraction from the hyperpolarization equipment and several hours’ lifetime of the 13C-labelled metabolic contrast agents at appropriate storage/transport conditions. Exemplified with [U-13C, d7]-D-glucose, we remotely produce hyperpolarized 13C-labelled metabolic contrast agents and generate above 10,000-fold liquid-state Magnetic Resonance signal enhancement at 9.4 T, keeping on-site only a simple dissolution device.
Highlights
Magnetic Resonance Imaging combined with hyperpolarized 13C-labelled metabolic contrast agents produced via dissolution Dynamic Nuclear Polarization can, non-invasively and in realtime, report on tissue specific aberrant metabolism
13C-magnetic resonance spectroscopy (MRS) and MRSI widespread use in the clinic is limited by low signal-tonoise ratio (SNR)
The custom-designed fluid path (CFP) allowed us to investigate, in a robust and reproducible way, all steps involved in a “remote DNP” experiment employing UV-induced radicals
Summary
Magnetic Resonance Imaging combined with hyperpolarized 13C-labelled metabolic contrast agents produced via dissolution Dynamic Nuclear Polarization can, non-invasively and in realtime, report on tissue specific aberrant metabolism. Metabolic imaging is still far from optimal in patients and blind to many cellular processes[5] Among those methods, 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is the current benchmark to assess hypo- or hypermetabolism in clinical practice, in particular for what concerns cancer diagnosis, staging, and treatment monitoring[6]. A complementary, direct, and specific way to track metabolism in vivo is to follow the fate of exogenous substrates by 13C magnetic resonance spectroscopy (MRS) or spectroscopic imaging (MRSI). These techniques allow characterization of tumors by measuring downstream metabolism enabled by good spectral resolution of the different metabolites[9]. This technique is challenged by difficult signal disentanglement at clinical magnetic field strengths
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