Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-<sup>13</sup>C]Pyruvate
Shiraz Nantogma, Henri de Maissin, Isaiah Adelabu, Abubakar Abdurraheem, Christopher Nelson, Nikita V. Chukanov, Oleg G. Salnikov, Igor V. Koptyug, Sören Lehmkuhl, Andreas B. Schmidt, Stephan Appelt, Thomas Theis, Eduard Y. Chekmenev
Abstract
13 C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of 13 C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1- 13 C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, 13 C Radiofrequency Amplification by Stimulated Emission of Radiation ( 13 C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor ( Q ) of 32 for sample concentrations as low as 0.125 M with 13 C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1- 13 C]pyruvate, which are separated by 10 ppm in 13 C NMR spectra. This is a good model system to study the simultaneous 13 C RASER signals of multiple 13 C species. This system models the metabolic production of hyperpolarized [1- 13 C]lactate from hyperpolarized [1- 13 C]pyruvate, which has a similar chemical shift difference. Our results show that 13 C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, 13 C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized 13 C signals. The reported results pave the way to novel sensing approaches of 13 C hyperpolarized pyruvate, potentially unlocking hyperpolarized 13 C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.