Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy Distinguishes Hepatocellular Carcinoma Genetic Subgroups In Vivo.

Motivation: Aberrant activation of the CTNNB1/Wnt pathway is a common molecular alteration in Hepatocellular Carcinoma (HCC) that has been found to impact patients' response to therapy; however, there is a deficiency of non-invasive biomarkers for stratifying HCC patients based on CTNNB1 mutational status. Goal(s): We sought to identify a novel non-invasive molecular imaging biomarker of CTNNB1/Wnt pathway mutation in HCCs. Approach: We assessed metabolic flux in clinically relevant HCC patient-derived xenografts in vivo using Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy. Results: We observed an 86% higher and 14% lower Hyperpolarized 1-13C Pyruvate conversion to Alanine and Lactate respectively in CTNNB1mutant HCCs compared to non-mutants. Impact: CTNNB1 mutant and non-mutant HCCs can be distinguished non-invasively by assessing Hyperpolarized-1-13C-Pyruvate flux to Alanine and Lactate. Our findings present a promising precision imaging strategy for patient stratification, with the potential to enhance treatment outcomes in HCC and other cancers.