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Abstract #3061

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

Bukola Yetunde Adebesin1, David Tischfield2, Ariful Islam2, Molly Sheehan2, Alexander I Zavriyev3, Aayush Bendre4, Daniel Ackerman2, Stephen Kadlecek2, and Terence Gade5
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 3Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 4Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA, United States, 5Department of Radiology. Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, United States

Synopsis

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas), Hepatocellular Carcinoma, Kinetic Modeling

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.

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Abstract

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