Toward Hyperpolarized ¹⁹ F Molecular Imaging via Reversible Exchange with Parahydrogen

Fluorine-19 has high NMR detection sensitivity-similar to that of protons-owing to its large gyromagnetic ratio and high natural abundance (100 %). Unlike protons, however, fluorine-19 (¹⁹ F) has a negligible occurrence in biological objects, as well as a more sensitive chemical shift. As a result, in vivo ¹⁹ F NMR spectroscopy and MR imaging offer advantages of negligible background signal and sensitive reporting of the local molecular environment. Here we report on NMR hyperpolarization of ¹⁹ F nuclei using reversible exchange reactions with parahydrogen gas as the source of nuclear spin order. NMR signals of 3-fluoropyridine were enhanced by ≈100 fold, corresponding to 0.3 % ¹⁹ F nuclear spin polarization (at 9.4 T), using about 50 % parahydrogen. While future optimization efforts will likely significantly increase the hyperpolarization levels, we already demonstrate the utility of ¹⁹ F hyperpolarization for high-resolution hyperpolarized ¹⁹ F imaging and hyperpolarized ¹⁹ F pH sensing.