Parahydrogen in Reversible Exchange Induces Long-Lived 15 N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole.

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.