Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology

Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma

“…The technique overcomes the low intrinsic sensitivity of 13 C magnetic resonance spectroscopy (MRS) that hampers in vivo studies because of long acquisition times. Indeed, one method for overcoming the low signal of 13 C-MRI is through the external hyperpolarization and injection of exogenous 13 C-labeled molecules, thereby enabling the imaging of central metabolic pathways such as glycolysis and the tricarboxylic acid cycle in real-time [156]. Hyperpolarization refers to a temporary increase in the proportion of nuclear spins aligned with the main magnetic field, thereby temporarily boosting the difference in the spin populations of the two energy states, which is directly linked to the sensitivity of NMR [156].…”

“…Indeed, one method for overcoming the low signal of 13 C-MRI is through the external hyperpolarization and injection of exogenous 13 C-labeled molecules, thereby enabling the imaging of central metabolic pathways such as glycolysis and the tricarboxylic acid cycle in real-time [156]. Hyperpolarization refers to a temporary increase in the proportion of nuclear spins aligned with the main magnetic field, thereby temporarily boosting the difference in the spin populations of the two energy states, which is directly linked to the sensitivity of NMR [156]. Several methods can be used to achieve hyperpolarization including dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP) [156].…”

“…Hyperpolarization refers to a temporary increase in the proportion of nuclear spins aligned with the main magnetic field, thereby temporarily boosting the difference in the spin populations of the two energy states, which is directly linked to the sensitivity of NMR [156]. Several methods can be used to achieve hyperpolarization including dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP) [156]. By this way, dynamic metabolic processes can be assessed in vivo by temporarily boosting the 13 C-NMR signal of some key metabolic substrates allowing the in vivo dynamic measurement of metabolic conversions [156][157][158].…”

“…Several methods can be used to achieve hyperpolarization including dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP) [156]. By this way, dynamic metabolic processes can be assessed in vivo by temporarily boosting the 13 C-NMR signal of some key metabolic substrates allowing the in vivo dynamic measurement of metabolic conversions [156][157][158]. The technique presents the unique advantage of probing real-time metabolic fluxes in vivo and therefore does not require excising the tumor sample.…”

“…The ratio is also influenced by the activity of monocarboxylate transporters, including MCT1 [162] and by the level of hypoxia [163]. Potential clinical applications of hyperpolarized 13 C-MRI in oncology include using metabolism to stratify tumors by grade, selecting therapeutic pathways based on tumor metabolic profiles, and detecting early treatment response through the imaging of shifts in metabolism that precede tumor structural changes, as recently reviewed [156]. The first human study with HP-[1-13 C]pyruvate demonstrated the safety of the method, along with the evidence that 13 C-MRI could identify a prostate tumor that was not visible with conventional 1 H-MRI [164].…”