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Significance Hyperpolarized [1-13 C]pyruvate magnetic resonance spectroscopic imaging (MRSI), which measures [1-13 C]pyruvate-to-[1-13 C]lactate conversion, has been widely explored as a metabolic-imaging modality interpreted to reflect LDHA activity and glycolytic flux. However, we show definitively that hyperpolarized [1-13 C]pyruvate-to-[1-13 C]lactate conversion rates are primarily a functional readout of [1-13 C]pyruvate transmembrane influx mediated by MCT1, providing a mechanistic reinterpretation and redirection of clinical translation.

proceedings of the national academy of sciences of the united states of america

Hyperpolarized [1- <sup>13</sup> C]pyruvate-to-[1- <sup>13</sup> C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane

Hyperpolarized [1- 13 C]pyruvate-to-[1- 13 C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane

Hyperpolarized [1- ¹³ C]pyruvate-to-[1- ¹³ C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane