A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as (13)C or (15)N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism-poor sensitivity-while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.

An extraordinary new technique using hyperpolarized 13 Clabeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-13 C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low-and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 F 11, 74 F 17, and 154 F 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional 13 C spectroscopic imaging studies of prostate cancer patients. [Cancer Res 2008;68(20):8607-15]