Biomedical Applications of the Dynamic Nuclear Polarization and Parahydrogen Induced Polarization Techniques for...

Since the first pioneering report of hyperpolarized [1-¹³C]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 ¹³C 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 ¹³C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogen-induced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key ¹³C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered.