UCSF

Hyperpolarized carbon-13 magnetic resonance (MR) is a molecular imaging technique that allows for real-time measurements of in vivo metabolism. Hyperpolarized carbon-13 pyruvate can be used to better characterize cancer aggressiveness and response to therapy by monitoring the production of hyperpolarized carbon-13 lactate. In the work described herein, measure both the overall production of hyperpolarized carbon-13 lactate and its extra- and intracellular distribution. Understanding this distribution leads to an understanding of cancer aggressiveness and metastatic potential. Thus, measuring the production and the distribution of hyperpolarized carbon-13 lactate may allow for the differentiation of benign and metastatic cancers.

We present bioreactor studies of two renal cell carcinoma (RCC) cell lines that show the efflux of hyperpolarized carbon-13 lactate play a significant role in the acquired signal and thus cannot be ignored. To study this distribution, we use a diffusion weighted pulsed gradient double spin echo sequence and a novel acquisition scheme for hyperpolarized carbon-13 metabolites. Given the highly dynamic signal changes characteristic of hyperpolarized carbon-13, we first verify the quantitative accuracy of the technique by measuring the diffusion coefficients of various hyperpolarized carbon-13 molecules in solution. Next, equipped with this technique, we measured the extra- and intracellular diffusion coefficients of various hyperpolarized carbon-13 metabolites in bioreactor studies with the same two RCC cell lines. We also assess the dynamic extra- and intracellular distribution of these hyperpolairzed carbon-13 metabolites in these cells and show that an inhibitor of the monocarboxylate transporter 4 (MCT4), which is responsible for the efflux of lactate and protons from the cytoplasm, increases the relative intracellular hyperpolarized carbon-13 lactate signal. Finally, we develop a methodology for diffusion weighted imaging and making apparent diffusion coefficient (ADC) maps of hyperpolarized carbon-13 metabolites on a clinical MR scanner. Using two novel acquisition techniques, we improve the accuracy and precision of these measurements. The work presented here will play an important role in assessing the tissue distribution of hyperpolarized carbon-13 metabolites, which will aid in the detection and characterization of cancer.