Parahydrogen in Reversible Exchange Induces Long-Lived <sup>15</sup>N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole
Keilian MacCulloch, Austin Browning, Patrick TomHon, Sören Lehmkuhl, Eduard Y. Chekmenev, Thomas Theis
Abstract
Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance 15 N polarization. Distinct substrates require unique optimal parameter sets, including temperature, magnetic field, or a shaped magnetic field profile. The fine tuning of these parameters for individual substrates is demonstrated here to maximize 15 N polarization. After optimization, including the usage of pulsed μT fields, the 15 N nuclei on common anticancer drugs, letrozole and anastrozole, can be polarized within 1–2 min. The hyperpolarization can exceed 10%, corresponding to 15 N signal enhancement of over 280,000-fold at a clinically relevant magnetic field of 1 T. This sensitivity gain enables polarization studies at naturally abundant 15 N enrichment level (0.4%). Moreover, the nitrile 15 N sites enable long-lasting polarization storage with [ 15 N] T 1 over 9 min, enabling signal detection from a single hyperpolarization cycle for over 30 min.