Molecular Profiling Distinguishes HCC Metabotypes Identified on Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy

Motivation: While hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy holds great promise for in vivo profiling of cellular metabolism, the molecular alterations underlying the observed metabolic phenotypes (metabotypes) remain understudied. Goal(s): We sought to characterize the molecular features contributing to the metabotypes identified on Hyperpolarized 1-13C Pyruvate MRS in hepatocellular carcinoma (HCC). Approach: We integrated transcriptomic and proteomic profiling together with hyperpolarized 1-13C Pyruvate MRS of HCC patient-derived xenografts (PDX) that recapitulate the diversity of gene and protein expression observed in patients. Results: Our data suggest that hyperpolarized 1-13C Pyruvate MRS distinguishes HCC metabotypes based on MCT4 expression. Impact: By applying clinically relevant PDX models of HCC harboring naturally occurring variability in expression of metabolic enzymes and transporters, our data provide critical insights into the interpretation of hyperpolarized 1-13C Pyruvate MRS during clinical translation.