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 18 F-FDG is a well-established method using the avid glucose uptake of tumor cells. 13 C MR spectroscopic imaging (MRSI) of hyperpolarized [1-13 C]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 18 F-FDG PET images for visualizing tumor metabolism in a rat model. Methods: 13 C 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 18 F-FDG PET images of the same animals was performed. The data were analyzed qualitatively (visual assessment) and quantitatively (magnitude and dynamics of 18 F-FDG uptake, 13 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 13 C 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 [1-13 C]pyruvate increases the sensitivity of MR imaging, signal-to-noise ratio constraints still apply for spatially and temporally resolved 13 C MRSI, emphasizing the need for further MR methodologic development. These first imaging data suggest the feasibility of 13 C MRSI for future clinical use.

Simultaneous Hyperpolarized 13C-Pyruvate MRI and 18F-FDG PET (HyperPET) in 10 Dogs with Cancer

“…Only preclinical comparisons have been performed and that being on separate PET and MR systems (25,26), with potential errors arising from the time difference between the examinations and the repositioning of the animal. Admittedly, it may not be with 18 F-FDG that the time difference is the largest challenge but with other potential PET tracers to be combined with CSI.…”

Combined hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients

“…There was no attempt to correlate 18 F FDG uptake and 13 C MRS across animals in the abovementioned studies. In a study of hepatocellular carcinoma tumor-bearing rats [17], tumors exhibited increased 18 F FDG uptake and locally increased pyruvate-to-lactate exchange. However, no correlation between PET and MRS data was observed across animals, possibly corresponding to the lack of correlation we observe for the canine carcinoma patients.…”

“…Group differences of [1- Only a few earlier studies have compared 18 F FDG PET and hyperpolarized [1-13 C]pyruvate MRS in animal models [16,17], and using sequential exams as opposed to simultaneous exams performed by us in the combined PET/MR clinical system. In a study of murine lymphoma treatment [16], a comparable decrease in 18 F FDG uptake and pyruvateto-lactate exchange was found 24 h after chemotherapy, with the decrease in 18 F FDG uptake appearing earliest.…”

“…However, PET is well-established clinically while hyperpolarized MRS is still at its infancy [11,[13][14][15]. The relation between 18 F FDG PET and hyperpolarized 13 C-pyruvate MRS in cancer has been explored in a limited number of preclinical studies using a sequential setup [13,[16][17][18], focusing on feasibility [17] and treatment effects [13,16,18]. With the availability of integrated PET and MRI in a clinical, whole-body system [19], simultaneous PET and hyperpolarized 13 C MRS (hyperPET) [20,21] F FDG uptake patterns [22], but have also observed canine cancer patients with a spatial mismatch [23].…”

Current Opportunities and Challenges of Magnetic Resonance Spectroscopy, Positron Emission Tomography, and Mass Spectrometry Imaging for Mapping Cancer MetabolismIn Vivo

“…Direct comparison of diagnostic accuracy of 11 C-acetate or 18 F-fluorocholine PET/CT versus hepatocyte-specific MRI on liver tumors would be of great interest; this area of research is still under investigation. Menzel et al recently reported a multimodal in vivo assessment of glucose metabolism in HCC tumors using hyperpolarized [1- 13 C]pyruvate DNP-MRS and 18 F-FDG PET [138]. The increased [1- 13 C]lactate signals in the tumor is correlated with corresponding enhanced 18F-FDG uptake.…”