Institute of Chemical Sciences and Engineering (ISIC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Jožef Stefan Institute, Ljubljana, Slovenia.
Nat Methods. 2019 Jun;16(6):526-532. doi: 10.1038/s41592-019-0421-z. Epub 2019 May 13.
Glucose is a major source of energy for most living organisms, and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited owing to the lack of robust tools. To date, positron-emission tomography imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings. Here, we report the development of a bioluminescent glucose-uptake probe for real-time, non-invasive longitudinal imaging of glucose absorption both in vitro and in vivo. In addition, we demonstrate that the sensitivity of our method is comparable with that of commonly used F-FDG-positron-emission-tomography tracers and validate the bioluminescent glucose-uptake probe as a tool for the identification of new glucose transport inhibitors. The new imaging reagent enables a wide range of applications in the fields of metabolism and drug development.
葡萄糖是大多数生物的主要能量来源,其摄取异常与许多病理状况有关。然而,由于缺乏稳健的工具,我们对与疾病相关的葡萄糖通量的理解是有限的。迄今为止,正电子发射断层扫描成像仍然是测量葡萄糖摄取的金标准,而在体内环境中,还没有用于非侵入性纵向成像这种重要代谢物的光学工具。在这里,我们报告了一种生物发光葡萄糖摄取探针的开发,用于实时、非侵入性地体外和体内纵向成像葡萄糖吸收。此外,我们证明了我们的方法的灵敏度可与常用的 F-FDG-正电子发射断层扫描示踪剂相媲美,并验证了生物发光葡萄糖摄取探针作为识别新的葡萄糖转运抑制剂的工具。这种新的成像试剂为代谢和药物开发领域的广泛应用提供了可能。