We developed methods for the preparation of hyperpolarized (HP) sterile [2-¹³C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-¹³C]pyruvate to [2-¹³C]lactate and [5-¹³C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-¹³C]pyruvate to [2-¹³C]lactate conversion rates (k_PL) were measured and showed similar but not identical inter-subject values. The k_PL measurements were equivalent with prior human HP [1-¹³C]pyruvate measurements.

This study developed a new approach to produce sterile, hyperpolarized [¹³C,¹⁵N₂]urea as a novel molecular imaging probe and applied it for first-ever healthy brain volunteer studies. Hyperpolarized [¹³C,¹⁵N₂]urea, as a small, metabolically inert molecule, offers significant advantages for perfusion imaging due to its endogenous nature and excellent safety profile. The developed methods achieved a hyperpolarized [¹³C,¹⁵N₂]urea solution (132 ± 6 mM) with 27.4 ± 5.6% polarization and a T₁ = 50.4 ± 0.2 s. In healthy brain volunteer studies, high-resolution ¹³C imaging captured blood flow with a spatial resolution of 7.76 × 7.76 × 15 (or 10) mm³ over ~1 min following hyperpolarized [¹³C,¹⁵N₂]urea injection, visualizing detailed vascular structures. Time-to-peak and centroid analyses showed consistent arterial and venous signal patterns across subjects. Findings suggest hyperpolarized [¹³C,¹⁵N₂]urea may have applications beyond brain imaging, including the non-invasive perfusion assessment in various organs, cancer microenvironment, and renal function, paving the way for clinical translation.

Hyperpolarized (HP) ¹³C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-¹³C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-¹³C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire ¹³C-labeled volumetric and dynamic images of [2-¹³C]pyruvate and downstream metabolites [5-¹³C]glutamate and [2-¹³C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (k_PL) and pyruvate-to-glutamate (k_PG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.