Quantitative Imaging of Pyruvate Metabolism in a Patient With Anaplastic Thyroid Cancer

Magnetic resonance imaging using hyperpolarized (HP) [1-¹³C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-¹³C₃]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-¹³C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics.

Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment.

This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo.