From Unlocking Pyruvate Hyperpolarization by Signal Amplification by Reversible Exchange (SABRE) to Clinical...

Hyperpolarization in magnetic resonance has emerged as a transformative approach to overcome the intrinsic sensitivity limits of NMR and MRI. Among the accessible hyperpolarization methods, Signal Amplification by Reversible Exchange (SABRE) has attracted considerable attention due to its rapidity, simplicity, and low operational cost. However, extending SABRE to biologically relevant metabolites notably pyruvate, remained challenging because carboxylates do not bind to the iridium-based catalysts. Over the past decade, series of mechanistic insights, catalyst innovations, and field-cycling strategies have been developed to redefin the hyperpolarization landscape, enabling robust SABRE-based polarization of ¹³C-labeled pyruvate. This review provides a comprehensive and coherent synthesis of these developments, beginning with the mechanistic foundations of SABRE, followed by an analysis of the limitations of early approaches, the breakthrough enabled by DMSO-assisted catalyst activation, and the evolution of SABRE-SHEATH, pulsed-field, SLIC-based, and LIGHT-SABRE methodologies. Particular emphasis is placed on catalyst structure-function relationships, substrate exchange kinetics, and the magnetic-field conditions governing polarization transfer. The review examines recent progress toward biocompatible formulations, catalyst recycling, and rapid purification workflows that have allowed the first in vivo metabolic imaging studies using SABRE-polarized pyruvate. The accumulated evidence demonstrates that SABRE is progressing rapidly from a chemical innovation to a practical hyperpolarization approach capable of complementing or even competing with dissolution DNP in preclinical metabolic imaging.