Multimodal assessment of in vivo metabolism with hyperpolarized [1- 13C]MR spectroscopy and 18F-FDG PET imaging in hepatocellular carcinoma tumor-bearing rats

Abstract

Abnormalities of tumor metabolism can be exploited for molecular imaging. PET imaging of 18F-FDG is a well-established method using the avid glucose uptake of tumor cells. 13C MR spectroscopic imaging (MRSI) of hyperpolarized [1-13C]pyruvate and its metabolites, meanwhile, represents a new method to study energy metabolism by visualizing, for example, the augmented lactate dehydrogenase activity in tumor cells. Because of rapid signal loss, this method underlies strict temporal limitations, and the acquisition of data-encoding spatial, temporal, and spectral information within this time frame-is challenging. The object of our study was to compare spectroscopic images with 18F-FDG PET images for visualizing tumor metabolism in a rat model. Methods: 13C MRSI with IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation) chemical shift imaging in combination with single-shot spiral acquisition was used to obtain dynamic data from 23 rats bearing a subcutaneous hepatocellular carcinoma and from reference regions of the same animals. Static and dynamic analysis of 18F-FDG PET images of the same animals was performed. The data were analyzed qualitatively (visual assessment) and quantitatively (magnitude and dynamics of 18F-FDG uptake, 13C MRSI dynamics, and physiologic parameters). Results: In most animals increased [1-13C]lactate signals in the tumor could be detected by simple display of integrated [1-13C]lactate images with corresponding enhanced 18F-FDG uptake. Low [1-13C]pyruvate or [1- 13C]lactate signals did not correlate with histologic or physiologic parameters. Significantly less pyruvate reached the tumors than the gastrointestinal tract, but in tumors a significantly higher amount of pyruvate was converted to lactate and alanine within seconds after intravenous administration. Conclusion: This study reveals that PET and 13C MRSI can be used to visualize increased glycolytic flux in malignant tissue. The combination of signals will allow the quantitative dissection of substrate metabolism, with respect to uptake and downstream metabolic pathways. Although hyperpolarized [1-13C]pyruvate increases the sensitivity of MR imaging, signal-to-noise ratio constraints still apply for spatially and temporally resolved 13C MRSI, emphasizing the need for further MR methodologic development. These first imaging data suggest the feasibility of 13C MRSI for future clinical use. © 2013 by the Society of Nuclear Medicine.