Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
NMR Biomed. 2021 Jul;34(7):e4532. doi: 10.1002/nbm.4532. Epub 2021 May 8.
Hyperpolarized (HP) [1- C]lactate is an attractive alternative to [1- 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 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 C cardiac study, C metabolic images were acquired following injections of HP [1- C]lactate in porcine hearts. Data were also acquired using HP [1- C]pyruvate for comparison. The C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No C pyruvate signal was detected in the experiments following injection of HP 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 T of [1- C]lactate as compared with [1- C]pyruvate and the additional enzyme-catalyzed metabolic conversion step before the C nuclei from [1- C]lactate were detected as C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart has been demonstrated.
高极化（HP）[1-¹³C]乳酸盐作为一种替代物，可用于在体研究心脏代谢，其比[1-¹³C]丙酮酸更有吸引力：它可以以更高的剂量安全给药，并且可以通过动态核极化达到与丙酮酸相似的极化程度。虽然已经在小动物模型中进行了使用 HP 乳酸盐的¹³C 心脏实验，但尚未在大动物模型或人类中进行演示。利用与首例人类 HP ¹³C 心脏研究相同的硬件和数据采集方法，在猪心内注射 HP [1-¹³C]乳酸盐后，获得了¹³C 代谢图像。还使用 HP [1-¹³C]丙酮酸采集了数据进行比较。¹³C 碳酸氢盐信号被定位到心肌，并且对于所有动物，两种底物的外观相似。在注射 HP ¹³C 乳酸盐后的实验中，未检测到¹³C 丙酮酸信号。注射乳酸盐的信号与噪声比（SNR）为注射丙酮酸的 SNR 的 88±4%，并且使用乳酸盐作为底物的实验中碳酸氢盐的 SNR 为使用丙酮酸作为底物的实验的 SNR 的 52±19%。较低的 SNR 可能是由于与[1-¹³C]丙酮酸相比，[1-¹³C]乳酸盐的 T1 较短，并且在¹³C 核从[1-¹³C]乳酸盐被检测为¹³C 碳酸氢盐之前，还存在额外的酶促代谢转化步骤。虽然仍然存在挑战，但已经证明 HP 乳酸盐作为人类心脏临床代谢成像的底物具有潜力。
