Purpose: In this study we aimed to characterize the metabolic signature of hepatocellular carcinoma (HCC) following an injection of hyperpolarized [1-13C]pyruvate. This was done as a pre-clinical step in the development of hyperpolarized MR as an imaging modality potentially enabling the detection of small HCC lesions (
Materials and Methods: Precision-cut liver slices (PCLS) from healthy and aged MDR2-KO mice were used. The MDR2-KO mouse is a well-established model for liver inflammatory carcinoma, sharing common features with human regenerative nodules and HCC. The slices were perfused and kept viable for several hours in a 10 mm NMR tube in an NMR spectrometer. 13C spectra were acquired with selective RF excitation following the injection of hyperpolarized [1-13C]pyruvate, and the enzymatic activity of lactate dehydrogenase (LDH) and alanine transaminase (ALT) were determined using the hyperpolarized signals of the newly formed [1-13C]lactate and [1-13C]alanine, respectively.
Results: The LDH/ALT enzymatic activities ratio was found to correlate to the progression of the liver disease, ranging from 0.40 ± 0.06, to 0.90 ± 0.27, to 1.84 ± 0.45 (n=3 animals in each group) in healthy liver, nodular parenchyma, and HCC, respectively.
Conclusion: Our results suggest that the enzymatic activities ratio LDH/ALT, as determined by monitoring the metabolism of their common hyperpolarized substrate ([1-13C]pyruvate), has the potential to characterize liver parenchyma and identify HCC. Further studies are needed to validate this biomarker in vivo.
