Lee Geonhui, Ruan Thomas, Wong Claudia, Deh Kofi, Abolarin Alli, Correa Alexander, Keshari Kayvan R, Jeong Sangmoo
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Bioengineering (Basel). 2022 Dec 21;10(1):14. doi: 10.3390/bioengineering10010014.
Abnormal metabolism is a hallmark of cancer cells. Accumulating evidence suggests that metabolic changes are likely to occur before other cellular responses in cancer cells upon drug treatment. Therefore, the metabolic activity or flux in cancer cells could be a potent biomarker for cancer detection and treatment monitoring. Magnetic resonance (MR)-based sensing technologies have been developed with hyperpolarized molecules for real-time flux analysis, but they still suffer from low sensitivity and throughput. To address this limitation, we have developed an innovative miniaturized MR coil, termed micro-slab MR coil, for simultaneous analysis of metabolic flux in multiple samples. Combining this approach with hyperpolarized probes, we were able to quantify the pyruvate-to-lactate flux in two different leukemic cell lines in a non-destructive manner, simultaneously. Further, we were able to rapidly assess flux changes with drug treatment in a single hyperpolarization experiment. This new multi-sample system has the potential to transform our ability to assess metabolic dynamics at scale.
代谢异常是癌细胞的一个标志。越来越多的证据表明，在药物治疗后，癌细胞中的代谢变化可能先于其他细胞反应发生。因此，癌细胞中的代谢活性或通量可能是癌症检测和治疗监测的有效生物标志物。基于磁共振（MR）的传感技术已通过超极化分子开发用于实时通量分析，但它们仍存在灵敏度和通量较低的问题。为了解决这一局限性，我们开发了一种创新的小型化MR线圈，称为微平板MR线圈，用于同时分析多个样品中的代谢通量。将这种方法与超极化探针相结合，我们能够以非破坏性方式同时量化两种不同白血病细胞系中丙酮酸到乳酸的通量。此外，我们能够在单次超极化实验中快速评估药物治疗引起的通量变化。这种新的多样品系统有可能改变我们大规模评估代谢动力学的能力。
