Aqueous-Phase Delivery of SLIC-SABRE Hyperpolarized [15N3]Metronidazole.

Metronidazole is an antiprotozoal antibiotic drug holding promise for tumor microenvironment analysis in hyperpolarized MRI due to its hypoxia-sensitive metabolism. Previous studies have explored the 15N hyperpolarization of metronidazole using dissolution dynamic nuclear polarization (d-DNP) and signal amplification by reversible exchange (SABRE). Here, we demonstrate that by using spin-lock-induced crossing (SLIC), 15N polarization levels up to 10-11% are achieved for 30 mM [15N3]metronidazole, improving polarization levels by a factor of 1.4 ± 0.1 compared to polarization levels achieved in conventional SABRE experiments under otherwise the same conditions. This polarization was harnessed to probe the purification of methanolic solutions of hyperpolarized [15N3]metronidazole, reducing the methanol concentration by 10-fold in the obtained aqueous solutions of 15N-hyperpolarized metronidazole, retaining up to 1/3 of initial polarization. This pilot study marks a substantial step toward the biomedical application of [15N3]metronidazole and is promising for the 15N-hyperpolarization of other substrates via SLIC and other SABRE strategies.