Hyperpolarized Carbon-13 MRI in Breast Cancer

Abstract

One of the hallmarks of cancer is metabolic reprogramming, including high levels of aerobic glycolysis (the Warburg effect). Pyruvate is a product of glucose metabolism, and 13C-MR imaging of the metabolism of hyperpolarized (HP) [1-13C]pyruvate (HP 13C-MRI) has been shown to be a potentially versatile tool for the clinical evaluation of tumor metabolism. Hyperpolarization of the 13C nuclear spin can increase the sensitivity of detection by 4–5 orders of magnitude. Therefore, following intravenous injection, the location of hyperpolarized 13C-labeled pyruvate in the body and its subsequent metabolism can be tracked using 13C-MRI. Hyperpolarized [13C]urea and [1,4-13C2]fumarate are also likely to translate to the clinic in the near future as tools for imaging tissue perfusion and post-treatment tumor cell death, respectively. For clinical breast imaging, HP 13C-MRI can be combined with 1H-MRI to address the need for detailed anatomical imaging combined with improved functional tumor phenotyping and very early identification of patients not responding to standard and novel neoadjuvant treatments. If the technical complexity of the hyperpolarization process and the relatively high associated costs can be reduced, then hyperpolarized 13C-MRI has the potential to become more widely available for large-scale clinical trials.

Targeting the Warburg Effect in Cancer: Where Do We Stand?

“…Thus, the prevalence of a high rate of glucose catabolism into lactate is the most widespread metabolic phenotype observed in cancer cells [ 3 ]. The presence of the Warburg effect has been described in most tumor types, including, but not limited to, glioblastoma [ 4 ], pancreas [ 5 ], breast [ 6 , 7 ], and cervix [ 8 ].…”