Hyperpolarized 13 C MRI : State of the Art and Future Directions

A metabolism is central to many human diseases, such as cancer, cardiovascular disease, diabetes, and a variety of inflammatory conditions. The most commonly used imaging strategy in the clinic for interrogating metabolism, particularly in cancer, is PET with the glucose analog 18F fluorodeoxyglucose (FDG). FDG PET provides information regarding tissue glucose uptake and has been highly clinically successful. However, it cannot help assess downstream metabolism, which may be useful in the diagnosis and treatment monitoring of a variety of diseases. Carbon 13 (13C) MRI is particularly attractive for metabolic imaging because carbon serves as the backbone of nearly all organic molecules, thus allowing the investigation of a wide range of biochemical processes that are relevant to human diseases. However, the low natural abundance of the 13C isotope, at 1.1%, has made in vivo imaging extremely challenging. This limitation has been overcome by the recent development of the dynamic nuclear polarization technique, which can dramatically, albeit temporarily, increase the signal of 13C-labeled molecules by more than 10 000 fold (1). Hyperpolarized (HP) 13C MRI has emerged as a powerful molecular imaging strategy that allows safe, nonradioactive, real-time, and pathway-specific investigation of dynamic metabolic and physiologic processes that were previously inaccessible to imaging. In this review, we will provide an overview of the methods of hyperpolarization and the various biologic processes that can be interrogated by using HP 13C probes, with a focus on HP 13C pyruvate. We will also summarize the technical and regulatory requirements of human HP 13C studies and highlight the emerging clinical applications of this molecular imaging technology. Hyperpolarization