Hyperpolarized MR peers into prostate cancer

The use of dissolution dynamic nuclear polarization has led scientists to a technique called hyperpolarization, which allows them to see real-time metabolic activity and vastly improves MR signal of miniscule cellular processes, according to a review published Aug. 28 in the Journal of Nuclear Medicine.

Prostate cancer is the most common cancer diagnosed in men in the U.S. An estimated 233,000 diagnoses are expected in 2014, according to the report. Using C-13 conjugated targets, David M. Wilson, MD, PhD, and John Kurhanewicz, PhD, from the University of California, San Francisco, have elucidated several characteristics of prostate cancer by hyperpolarizing the agents and evaluating their course of action via C-13 nuclear MR (NMR). The signal of polarized C-13 radiolabeled substrates are on the level of 50,000 times that of unpolarized agents. The technique has already been developed through preliminary human trials.

“The recent first-in-man hyperpolarized C-13 MR imaging study in prostate cancer patients has confirmed the clinical potential of this remarkable technology,” wrote the authors.

Hyperpolarized C-13 MR is being used to detect the metabolic reprogramming of cancer. MR spectroscopic imaging (MRSI) is being used to track important metabolic changes within the prostate to create a visual map of resonances linked to polyamines, choline, creatine and citrate.

“This concept differs from the traditional view of cancer as a primarily genetic, proliferative phenomenon,” wrote the researchers. “The focus of this mini review is identification of several of the metabolic shifts seen in cancer that may be exploited for diagnostic purposes, in particular by the agents and platforms developed for hyperpolarized C-13 [MRSI].”

C-13 pyruvate, a product of glycolysis, is an ideal biomarker due to cancer’s preference for aerobic glycolysis and its hunger for glutamine and altered carbon use. These cancer cells also have the ability to pull in intracellular antioxidants. All of these traits are all influenced by oncogenes, namely PI3K/AKT, MYC, and HIF-1, and by the suppression of genes that typically keep cellular processes in check, like P53.  While several substrates have been studied, pyruvate has been the most successful.

“Therefore, use of fast C-13 MR after injection of hyperpolarized [1-13C]pyruvate to measure this metabolic switch and its relationship to cancer aggressiveness and therapeutic response makes biologic sense.”

Future human trials will focus on developing new hyperpolarized agents, better polarization techniques and innovative means of agent delivery. MR technology will also have to grow, with better coil design, MR pulse sequences and the possibility of hybrid imaging.