Cardiac metabolic imaging using hyperpolarized [1-13 C]lactate as a substrate

Abstract

Hyperpolarized (HP) [1-¹³ C]lactate is an attractive alternative to [1-¹³ C]pyruvate as a substrate to investigate cardiac metabolism in vivo: it can be administered safely at a higher dose and can be polarized to a degree similar to pyruvate via dynamic nuclear polarization. While ¹³ C cardiac experiments using HP lactate have been performed in small animal models, they have not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods as the first human HP ¹³ C cardiac study, ¹³ C metabolic images were acquired following injections of HP [1-¹³ C]lactate in porcine hearts. Data were also acquired using HP [1-¹³ C]pyruvate for comparison. The ¹³ C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No ¹³ C pyruvate signal was detected in the experiments following injection of HP ¹³ C lactate. The signal-to-noise ratio (SNR) of injected lactate was 88 ± 4% of the SNR of injected pyruvate, and the SNR of bicarbonate in the experiments using lactate as the substrate was 52 ± 19% of the SNR in the experiments using pyruvate as the substrate. The lower SNR was likely due to the shorter T₁ of [1-¹³ C]lactate as compared with [1-¹³ C]pyruvate and the additional enzyme-catalyzed metabolic conversion step before the ¹³ C nuclei from [1-¹³ C]lactate were detected as ¹³ C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart has been demonstrated.

Keywords: 13C metabolic imaging; DNP; heart; lactic acid; metabolism.