Abstract
Since the first pioneering report of hyperpolarized [1-(13)C]pyruvate magnetic resonance imaging (MRI) of the Warburg effect in prostate cancer patients, clinical dissemination of the technique has been rapid; close to 10 sites worldwide now possess a polarizer fit for the clinic, and more than 30 clinical trials, predominantly for oncological applications, are already registered on the US and European clinical trials databases. Hyperpolarized (13)C probes to study pathophysiological processes beyond the Warburg effect, including tricarboxylic acid cycle metabolism, intra-cellular pH and cellular necrosis have also been demonstrated in the preclinical arena and are pending clinical translation, and the simultaneous injection of multiple co-polarized agents is opening the door to high-sensitivity, multi-functional molecular MRI with a single dose. Here, we review the biomedical applications to date of the two polarization methods that have been used for in vivo hyperpolarized (13)C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogen-induced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key (13)C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered.